Global warming and obesity: External heat exposure as a modulator of energy balance

Abstract

In obesity research, the importance of core body temperature (CBT) regulation is often neglected. CBT thermogenic regulation, however, plays a crucial role in heat management through convection, radiation, and conduction processes to remove heat from the body, as well as metabolic processes that sequester heat through lipogenesis. This review emphasizes that even small changes in CBT can significantly impact metabolic events ranging from ATP production to fat deposition. Accordingly, a case is made that physical events, such as external heat exposure, also impact body compositional changes, as do work and metabolic processes. Examples are provided that suggest that independent diet and exercise, where one lives, can have an impact on body composition and obesity. For example, below 35 degrees of the earth's latitude, obesity rates are often 40 percent or greater among adults. However, in regions between 45 and 50 degrees latitude, such as the US‐Canadian border, obesity rates are 25%–30%.

Core body temperature regulation can significantly influence metabolic processes to maintain energy balance. For example, geographic and environmental factors (global warming) can affect obesity rates and can be tracked along latitudinal boundaries.

Abbreviations

BMR

basal metabolic rate

CBT

core body temperature

GMST

global mean surface temperatures

RMR

resting metabolic rates

SA/V

surface to volume ratio

TNZ

minimal basal energy expenditure at rest without active thermogenesis or heat dissipation

TRP

integral membrane proteins associated with transient receptor potential channels

1. INTRODUCTION

1.1. Climate change and associated health challenges

The co‐occurrence of three threats to global health—obesity, undernutrition, and climate change is highlighted in a 2019 Lancet Commission report and labeled as a worldwide syndemic. ¹ The concept of syndemics holds that two or more health conditions interact in complex ways and may share common drivers interacting synergistically with negative impacts on human health. Obesity sits within a sociobiologic context that has been broadly discussed. However, less attention has been given to human health feedback loops or biological mechanisms whereby climate change and global warming can influence energy regulation.

An et al. ² have described the relationships between global warming and obesity, reviewing 50 studies (20 of which were original articles) and proposed a conceptual model of social and biological determinants, many of which were either correlated or influenced each other in a bidirectional manner. Koch et al. ³ have also discussed possible effects and pathways where global warming can influence adiposity, including the potential obesogenic consequences of alterations in adaptive thermogenesis and metabolic regulation.

Likewise, during the past decade, numerous research articles have addressed the topic of metabolic regulation in the context of complex biochemical mechanisms critical to energy homeostasis. In clinical settings, such articles have used mostly biochemical parameters as indices, such as blood glucose, lipid metabolites, energy regulation hormones, or markers for inflammation and cell signaling components.^{4, 5, 6, 7} Although essential to formulating selected clinical judgments, such criteria seldom directly address the fundamental principles that drive energy balance and homeostasis, that is, physical properties critical to thermogenic regulation and thermodynamic principles. Moreover, relying on only biochemical parameters without considering the underlying physical principles can lead to conceptual and clinical misinterpretations ascribed to biological processes.

The subsequent sections describe non‐isometric relationships: allometry, quarter‐power relationships, and fractal networks, followed by surface area‐to‐volume relationships. The goal of the initial sections is to provide background for the section dealing with thermogenic regulation and maintenance of metabolic set‐points, such as core body temperature. It will be emphasized that it is essential to conceptualize heat (i.e., calories, Joules, or Watts) as both metabolically and physically derived.

2. ALLOMETRY AND NUTRITION

2.1. Quarter power relationships

When expressed relative to energy needs, the requirements for animals generally are identical or similar. For example, the metabolic rate of organisms relative to their mass to the ¾ power can be estimated to scale over ~27 orders of magnitude (Figure 1), that is, from cellular components to unicellular organisms to large mammals.^{8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20} Consider that a young adult mouse (~20 g) consumes 4–5 g of food daily to meet its daily thermal energy of ~20–25 Kcals (~80–100 KJ). If expressed per 2000 Kcal of diet, the mouse requirements for most nutrients correspond within the same orders of magnitude as the human requirements. Similarly, predicting possible drug and selected nutrient toxicity limits can be in error by as much as two orders of magnitude or more for humans using isometric comparisons from effects in small animals. ¹⁹ As an internal validation, it is also possible to demonstrate that the daily production and turnover of vitamins for animals that can synthesize them (e.g., ascorbic acid) may be used to predict the daily dietary need for animals that require the vitamin. ²¹ Allometric scaling also has utility within species. In human studies, regulatory guidelines and research protocols consistently use weight‐based dosing. This is partly done to facilitate comparison between studies and simplify the regulatory approval process for drugs and chemicals. Dosages and selected effects of nutrients can easily result in conceptual distortions when expressed directly per weight or mass. ²² As an example, it is often routine to compare the resting metabolic rate (RMR) of obese individuals to those of “normal or reference” individuals of the same height.

FIGURE 1.

The basal metabolic rate (in Watts) versus Mass (in Grams). For animals, the metabolic rate scales to mass to the 3/4 power across ~27 orders of magnitude.^{7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20} The relationship allows scaling from small respiratory particles to very large mammals. Moreover, energy utilization by unicellular components and poikilothermic (ectothermic) organisms allometrically scale when adjustments are made to normalize temperature. Although factors such as developmental stage, body composition, the surface area to mass ratio, body shape, and appendages may influence the relationship, the most critical variables, size and temperature, account for most of the variation.^{12, 13}

The weights of “reference women and men” are often taken as 55 or 65 kg, respectively. Using isometric projections, the estimated RMR for 100–150 kg individuals is ~1.7 to ~2.5‐fold higher. However, in allometric approaches (¾ power comparisons), an estimated RMR for 100–150 kg individuals is less. That is, ~1.4 to 2‐fold higher. The direct‐isometric projections result in 18–20 percent overestimates of energy, the equivalent of ~400–500 Kcal. Although small in magnitude, in some settings, errors in interpreting RMR measurements may compromise estimates of daily energy needs for research interventions and clinical care, the creation of effective dietary plans for metabolic disorders, critical illnesses, or postsurgical nutritional needs.^{22, 23, 24} As Haddad et al. ²⁵ have observed, allometric scaling of resting energy expenditure removes body composition‐associated biases and should be considered in obesity and weight‐based intervention studies. Further, a nonlinear scaling relationship of total daily energy expenditure to body mass consistent with previous allometric research was confirmed in 2501 participants from doubly labeled water studies. ²⁶ The scaling relationship can even be applied to survey data, that is, in weight‐stable adults, obese individuals do not underreport dietary intake to a greater extent than nonobese individuals, observations that contradict isometric studies demonstrating that obesity is associated with a greater degree of underreporting. ²⁷

2.2. Fractal networks

An appreciation for fractal networks evolved from the insights of Leonardo Bonacci, known as Fibonacci (c. 1170–1240–50), Galileo (c. 1564–1642), and later, the French mathematician, François Édouard Anatole Lucas (1842–1891).^{28, 29, 30, 31, 32, 33, 34, 35, 36} As numerical sequences, each number in the progression is the sum of the preceding two; for example, 0, 1, 1, 2, 3, 5, 8, 13, 21, 34, 55, 89, 144, 233, 377, Fn = Fn‐1 + Fn‐2. Such sequences are often coined as the Fibonacci‐Lucas mathematical progressions. As the sequences proceed, the quotient between each successive reclusive pair of numbers approximates 1.618, or its inverse 0.618. The quotient is often designated as the golden ratio, mean, or proportion (ϕ).

Fractal patterns and sequences occur extensively in natural phenomena (Figure 2), such as the spirals of shells, the branching of plants, and biological and terrestrial flow systems.^{30, 31, 32, 36} Even at the tissue and cellular levels, there is transition between dispersed individual and multicellular collectives, which evolve as fractal‐like branching clusters during development, proliferation, growth, and repair. All tissues and cells (plants and animals) have hierarchically branched resource distribution networks (fractalated structures) for rapid delivery of nutrients and heat transfer.^{34, 35, 36}

FIGURE 2.

Fractals. Fractals are structures or patterns exhibiting self‐similar scaling. In nature, many complex systems display fractal‐like patterns, such as river networks, for example, the Mississippi basin (A), capillaries (B), trees (C), lung structures (D), and mountain ranges. These structures exhibit similar shapes or patterns when observed at different magnifications (E) from galaxies (F) to snails (G) to hurricanes (H). They have self‐similar and allometric dimensions. The mathematical properties of Fibonacci‐like sequences (self‐similarity, recursive patterns, and spiral geometries) are deeply intertwined with the principles that underlie fractal geometry, and the self‐similar patterns found in nature.^{30, 31, 32, 36} Physiological transport and flow are maximized by fractalization (e.g., the efficient transport of nutrients and oxygen). Fractalization also allows plants to maximize their exposure to sunlight.

Fractal networks offer several advantages, including increased efficiency in thermogenic heat and nutrient flow that can be controlled in a homeostatic fashion. They also add an extra fourth spatial and temporal dimension to life, which is why quarter‐power scaling has emerged as a convective heat and nutrient flow strategy that connects nutrition‐related energy intake to metabolism. Moreover, fractal networks define the limits for growth in some species. For instance, in mammals, the screw or bumblebee bat, which weighs 1–2 g, is the smallest mammal in which pulsative capillary blood flow can be maintained. ³⁷ If capillary radii become too narrow, the blood's viscosity dominates, inhibiting sufficient nutrient and heat flow. As shown in Figure 1, beyond this limit, energy needs and body weight for mammals scale up to eight orders of magnitude from screws to whales, the largest mammal.

Further, fractal networks lead to increased internal surface area compared to other designs. The surface area of fractalated networks provides more contact with fluids (e.g., from arteries, capillaries, and veins), improving heat and nutrient transfer efficiency. In addition, the intricate patterns of fractal networks induce turbulence in the flowing fluid. Turbulence is desirable in heat transfer because it disrupts the thin layer of fluid that adheres to the object's surface, often acting as an insulator. Fractal networks also optimize fluid flow distribution, ensuring that all network parts are effectively utilized for heat transfer. Despite their complexity, fractal networks require less material volume.

2.3. Surface area to volume relationships

Max Rubner introduced the “surface hypothesis” in 1883, which states the metabolic rate of homothermic birds and mammals appeared proportional to body surface area [cf. Ref. 38]. Rubner's observations and concepts that evolved from Newtonian physics provided the foundation for the initial studies focusing on interdependencies critical to growth and form. Many studies observed that very low or high surface area‐to‐volume ratios made it challenging to dissipate excess body heat, notably when the environmental temperature exceeded normal body temperatures (Figure 3). For example, it is challenging for large animals residing in hot climates to find habitats that support normal thermoregulation. In animals with a relatively large muscle mass, generating heat during activity exacerbates maintaining a stable body temperature. While some larger animals have adaptations for cooling (e.g., sweating in humans, panting in dogs, and increased conductive surfaces, such as elephant‐like ears), these mechanisms can be inefficient in external environments, exceeding those of the animal's core body temperature. Likewise, small animals with higher surface area‐to‐volume ratios in cold climates adopt specific behaviors, such as huddling, burrowing, torpor, or seeking shelter to conserve heat. Torpor is analogous to overnight hibernation. For example, on a cold night, hummingbirds often cannot consume enough calories to maintain their body temperature throughout the night. Instead, they allow their body temperature to drop to reduce metabolic rate. ³⁸

FIGURE 3.

Surface to volume (SA/V) ratios for animals. (A) The SA/V for a given animal may be approximated by selecting a general shape and applying appropriate geometric formulas. The diversity of animal shapes and sizes make exact calculations difficult. However, as an animal's size increases, the SA/V ratio decreases (B). This principle has significant implications for the physiology, behavioral attributes, and ecology that influence environment interactions and regulate thermogenic properties.^{39, 40}

In addition, other adaptations include the influence of temperature on phenotypic modifications. For example, in the late 1800s, Joel Asaph Allen observed that animals adapted to cold climates have shorter and thicker limbs and bodily appendages than animals adapted to warm climates. From his observation, Allen's rule evolved, which states that the body surface‐area‐to‐volume ratio for homoeothermic animals varies with the average temperature of the habitat to which they eventually adapt. A corollary to Allen's rule is Bergmann's rule, which states that within a broadly distributed taxonomic clade, populations and species of larger size are found in colder environments, and species of smaller size are found in warmer regions.^{41, 42, 43} Moreover, as Fröhlich et al. ⁴⁴ note, there are allometric trade‐offs between Bergmann's and Allen's rules, resulting in numerous adaptive strategies for thermoregulation. Few of these strategies, however, address the adaptations needed in response to the current rate of climate change, which are described in subsequent sections of this review.

To give metabolism an entropic focus, the process of catabolism can be viewed as an increase in the “number of microstates available to the system” and “disorder” as the amount of energy not available for productive work. Entropy increases over time in closed systems (e.g., an organismal body), and a state of disorder evolves (e.g., developmental and aging processes). Paradoxically, while contributing to entropy, living organisms also retard its impact by using some of the entropic energy to build molecules that aid in organizing cellular structures, such as components of cell membranes, reticular structures, and organelles. ⁴⁵ Entropic energy also improves catalytic behavior by optimizing cellular temperatures when exposed to cold or hot external environments. When regulated, metabolically derived entropic energy allows organisms to maintain a state of dynamic equilibrium, thus reducing internal entropy. As will be developed in subsequent sections, maintaining a dynamic equilibrium state is critical in defending fluctuations due to external temperature changes. To give the metabolism an entropic focus, view the process of catabolism as an increase in the “number of microstates available to the system” and “disorder” as the amount of energy not available for productive work. Further, entropy increases over time in closed systems (e.g., an organismal body), and a state of disorder evolves (e.g., developmental and aging processes).

2.4. Dynamic equilibria

The second law of thermodynamics is fundamental in defining dynamic equilibrium. During dynamic equilibria, some energy dissipating in transfer and transformation reactions increases the system's entropy (Figure 4). A critical phenomenon in this context is the coupling and uncoupling of mitochondrial proton gradients. Uncoupling above the core body temperature (CBT) can reduce ATP production. Such uncoupling is facilitated by the expression and actions of uncoupling proteins like UCP1, a common thread across diverse organisms.^{46, 47} A prime example is the heat generated from brown fat, which involves UCP1 uncoupling. When uncoupling occurs, the energy from electron transport is released as heat instead of being used to synthesize ATP. Increasing the temperature above the body's core temperature causes increased mitochondrial inner membrane permeability and impaired oxidative phosphorylation. Mitochondria function optimally in homothermic animals at ~50°C, about 10°C hotter than body core temperature. ⁴⁸ If the heat generated by mitochondria is not easily convected from cells or the whole body, the sustained elevation in temperature during mitochondrial metabolism can lead to:

1. Denaturation of proteins, including mitochondrial enzymes,

2. Reduced oxygen utilization as H₂O, which enhances ROS production.

3. Reduced ability to engage in critical work due to decreased ATP production,

4. Abnormal alterations in the rates of enzymatic reactions that are crucial for various metabolic pathways.

FIGURE 4.

Thermogenic regulation. The concept of thermogenic energy flow links metabolic regulation to principles of the second law of thermodynamics, that is, in any energy transformation, there is an increase in entropy. In cellular metabolism, energy flows through biochemical pathways undergoing transformations, such as the catabolism of complex molecules to simpler ones or their anabolism from simpler precursors. Just as the second law of thermodynamics imposes constraints to reach equilibrium and maintain a state of maximum entropy, metabolic regulation operates within the limitations imposed by biochemical and physiological factors that dictate transformations critical to sustaining life processes. Conceptually, ΔH is analogous to the heat of combustion or physiological fuel values, TΔS is analogous to metabolic energy flow, and ΔG (Gibb's free energy) is the work associated with metabolic processes and heat generation. Excessive external heat and cold, like food sources, can modulate the ATP levels (energy) associated with work, growth, development, and heat for optimal catalysis. Too much heat, whether from internal or external sources, can result in hyperthermia. Hypothermia can occur when abnormal internal heat levels are needed to maintain normal thermogenic levels because of cold exposure.

Importantly, uncoupling begins when the body core temperature is elevated and sustained by as few as 2°C, that is, to 100–102°F. Such hyperthermia can eventually lead to faster metabolic rates, increased heart rate, and a higher oxygen demand, potentially leading to cellular damage (Figure 5).

FIGURE 5.

Core temperature regulation. Excessive external heat and cold, like food sources, can modulate the ATP levels (energy) associated with work, growth, development, and heat for optimal catalysis. Too much heat, whether from internal or external sources, can result in hyperthermia. In contrast, hypothermia can occur when abnormal internal heat levels are needed to maintain normal thermogenic levels because of cold exposure. Thermogenic regulation and maintenance of the CBT temperature is controlled by thermogenic setpoints. Components of the thermogenesis that aid or influence the CBT are as follows: (1) Heat generated from intestinal food digestion (obligatory or dietary‐induced thermogenesis); (2) The equilibrium between core temperature and external temperature, for which equilibrium is controlled by skin receptors that aid in activating neurological and hormonal signals that regulate thermogenic heat flux; (3) Shivering thermogenesis in skeletal muscle, non‐shivering thermogenesis in beige and brown fat, and lipogenesis when heat is in excess. Heat from metabolism flows via radiant processes or convection by means of capillary vessels and cellular reticular networks. Excess heat leaves the body by conduction from the skin's surface unless compromised by excessive humidity.

For reference, the Q₁₀ coefficient is often used to quantify the temperature sensitivity of chemical reactions [ref]. For many modeling studies, the Q₁₀ coefficient is usually taken as a 1.5‐ to 2‐fold change per 10‐^oC temperature change. When applied to specific enzyme reactions or processes, such as changes in the integral membrane proteins associated with transient receptor potential channels (TRP). Going from a body core temperature of 36.1°C (97°F) to 40°C (104°F) can increase reaction rates or processes critical to ion transport by 20–40 percent of expected values.

The TRP ion channels are crucial in the signaling cascades and neurosensory processes of all of the five senses. If TRPs malfunction, abnormal calcium or calcium/sodium influx or efflux occurs, affecting multiple signaling pathways. TRP channels are activated in response to various stimuli, including changes in oxidative stress, temperature, mechanical forces, hormones, neurotransmitters, and voltage.^{47, 49, 50, 51}

Disrupting the integrity of cell membrane TRPs can also lead to abnormal cell permeability and changes in neural excitation potentials. The schema highlights examples associated with the cellular response to oxidative stress. The control of ion flux through such channels often results from Cys‐Cys bond redox. Additionally, many TRP channels work together with other signaling proteins. While the impact may not be direct, decreasing ATP production with corresponding alterations in thermogenic regulation can cause weight gain.

3. REGULATION OF THERMOGENETIC AND METABOLIC SET POINTS

The regulation of thermogenesis is closely tied to entropic heat production, allowing for proper dissipation of heat generated by metabolism. Regulation occurs above or below an organism's thermoneutral zones to maintain a consistent core body temperature^{52, 53, 54, 55, 56, 57, 58, 59}; cf., (Figures 5 and 6). In this regard, the downregulation of adipose tissue genes associated with thermogenic regulation is a potential mechanism that can contribute to developing adiposity with increasing global temperatures. Brown adipose tissue and “beige” adipocytes express genes for transcription factors and proteins such as UCP1 involved in thermogenesis and defense of the CBT. ⁴⁷ Abnormal elevations of the CBT can eventually cause reductions in brown and beige adipose and increases in white adipose, although there are exceptions. For example, local hyperthermia therapy can elicit a transient heat shock response, which causes white adipose to upregulate heat shock transcription factors that may induce white fat browning (i.e., mitochondriogenesis). ⁶⁰

FIGURE 6.

Energy expenditure and energy intake at different ambient temperatures. The thermoneutral zone (TNZ) is the minimal basal energy expenditure at rest without active thermogenesis or heat dissipation. As temperature increases above the TNZ, energy expenditure increases, and the desire for food energy decreases. Note that TNZ is often reported to be lower for obese humans than lean humans.^{52, 53} The highest ambient temperature from which recovery from hyperthermia is possible depends on factors, including the individual's health, hydration status, and duration of exposure. Generally, humans can withstand higher temperatures for short durations, but exposure to temperatures above 100°F (40°C) can result in hyperthermia and reductions in ATP production. Hypothermia is accelerated when the body temperature drops below 95°F (35°C), that is, only one to two degrees less than the TNZ.

Nevertheless, excessive external heat or cold exposure must be considered. Each can significantly impact the body's ATP production efficiency and the maintenance of a CBT, which is essential to regulating cellular processes, optimizing enzyme function, and sustaining optimal metabolic rates. As outlined in the previous section, higher‐than‐normal body temperatures can cause enzymes to denature. Cold temperatures slow down enzymatic reactions, decreasing metabolic rates and, consequently, the amount of ATP available for energy‐demanding processes such as muscle contraction, growth, and cellular repair. Excessive heat causes cellular membranes to become more fluid, potentially disrupting electron transport in mitochondria essential for ATP production. Instead, there is increased production of heat. In both hot and cold environments, the body adjusts its basal metabolic rate (BMR) to manage heat or cold stress.

4. RELATIONSHIPS BETWEEN EXTERNAL HEAT EXPOSURE AND WEIGHT GAIN

Figure 7 depicts changes in annual average temperatures in the USA by latitude and its potential impact on weight gain. In the United States, for every 10‐degree increase in latitude, there is a decrease in obesity, which is strongly related to changes in temperature. A similar response (increased percentage in obesity vs. latitude) is also observed for the counties defining the central valleys of Florida and California [cf. Refs. ^{61, 62, 63}].

FIGURE 7.

Relationship between latitude, temperature, and obesity. (A) The increase in annual temperature varies depending on various factors, such as the proximity to large bodies of water, altitude, prevailing winds, and geographical features. On average, each degree of latitude (~111 km or ~70 miles) represents a.0.6°C (~1.1°F) decrease in temperature per degree of latitude. (B) Regarding obesity in the United States, each data point represents a state in the United States. Note that Florida (filled circles) and California (filled boxes) extend over 10 degrees of latitude in length. The average percentage of obesity for the three most northern and southern counties for each state is shown.^{61, 62, 63} Further, only data from Central Valley counties are included because coastal and mountainous areas tend to be cooler and less humid. (C) Starting in the 80s and 90s, there has been a 1.5–2.0‐centigrade increase in the average temperature of most states. ⁶⁴ For perspective the rate of warming since 1982 is more than three times the rate prior to 1980–1990. Regarding, obesity, in the early 1960s, roughly 13% of the adult population in the USA was considered obese by the Centers for Disease Control and Prevention [https://www.cdc.gov/obesity/index.html]. As a percentage, adult obesity rose 1.6‐fold to ~20 percent in the early 1990s. Note that in 1990 and 2021, the percentage change in the number of obese adults closely correlates with changes in temperature; however, for the shift to higher temperature (year 2022 vs. year 1990), the percentage for adult obesity now ranges from 35 to ~50 percent. The obesity data are from the International Obesity Task Force, associated with the International Association for the Study of Obesity. ⁶⁴

As a specific reference, obesity in California adults is approximately 30 percent, with most living in areas close to the coast or elevated and the mountainous regions where the average summer temperature is 68–72°F. In the California Valley, the percentage of obesity correlates with average summer temperatures (Figure 8).

FIGURE 8.

Obesity and average summer temperatures in California. In California, when counties are examined in which most of the population lives below 2000 feet (e.g., the central valley), temperature changes follow changes in latitude. Imperial County is 33 degrees latitude, whereas Siskiyou is 42 degrees latitude. The data suggest a one‐degree change in the average summer temperature appears associated with a ~0.5 percent increase in obesity. For reference, in the cooler coastal and mountainous areas, where the average summer temperatures are ~70–75°F, obesity rates are 30 percent or less. Data regarding the percentage of obesity in each CA county may be obtained from the California Department of Public Health (https://www.cdph.ca.gov/Programs/CCDPHP/DCDIC/NEOPB/Pages/SNAPEdCountyProfileDashboard.aspx) and data for summer temperatures from the National Centers for Environmental Information‐National Oceanic and Atmospheric Administration (https://www.ncei.noaa.gov/access/monitoring/climate‐at‐a‐glance/county/mapping/4/tmax/202208/12/rank).

An important point to consider in this data is that over the past four decades, the obesity rate has more than doubled, with a notable acceleration in the 1990s and early 2000s (Figure 9). In the 1950s to 1970s, the obesity rate was 10–20 percent of the adult population. Currently, the percentage of obese adults in the United States ranges from 30 to ~50 percent. A prediction by the International Association for the Study of Obesity suggests by 2050 the percentage of adults with obesity will be nearer to 65 percent. ⁶⁴ Moreover, a positive association between the prevalence of obesity and mean annual temperature has been demonstrated in a population‐based survey of over 5000 adult subjects in 100 cluster areas of Spain. ⁶⁵ Also, a systematic analysis of 114 observational studies among elementary school children in 39 European countries demonstrates trends in body weight by climate zone, ⁶⁶ which have become most apparent in the past 20 years.

FIGURE 9.

The global temperature change and obesity. (A) The average temperature increase has been striking starting in the 1980s, (B) During this period, the percentage of those who can be classified as obese has increased two‐fold or more,^{2, 3, 64} also refer to Figure 7C.

4.1. Effects of temperature on oxygen consumption and relative ATP production

To better define mechanisms in the context of global warming, the effects of temperature on oxygen consumption and relative ATP production efficiency were estimated using data and concepts from the sources described in Table 1 and the legend for Figure 10. The data sources address oxygen consumption during different stages of mitochondrial respiration versus temperature changes. Mitochondrial complex II oxygen consumption changes in response to temperature variations (cf., Figure 10A). Complex II oxidizes succinate to fumarate and transfers electrons into the electron transport chain with increasing temperature. When oligomycin is used to inhibit ATP production, the remaining oxygen in the system was calculated to determine the impact of temperature on proton leakage across the inner mitochondrial membrane. Again, a positive correlation between rising temperatures and proton leakage was observed, suggesting the electron gradient was compromised (Figure 10B).

TABLE 1.

Effects of temperature on mitochondrial oxygen consumption, relative ATP production, and thermogenesis.

Source	Description
1. Leo et al. (2017) Mitochondrial acclimation potential to ocean acidification and warming of Polar cod (Boreogadus saida) and Atlantic cod (Gadus morhua). Front Zool. 14:21 [cf. ref. 67, 68].	Using polar and Atlantic cod fish as experimental models, it is demonstrated that endothermic polar cod are capable of survival over only a narrow range of temperatures. Mitochondrial efficiency (measured by oxygen consumption) decreases at >6–8°C, while Atlantic cod mitochondria are resilient at those temperatures. Polar cod also has a lower acclimation potential to warming than Atlantic cod. An implication is that Atlantic cod may eventually replace Polar cod if ocean warming increases as predicted. Data from this reference were used for Figure 10A.
2. Dawson et al. (2022). Inter‐individual variation in mitochondrial phosphorylation efficiency predicts growth rates in ectotherms at high temperatures. FASEB Journal: 36, e22333 [cf. ref. 68].	Demonstrates that aquatic ectotherms are vulnerable to external heat because their metabolic demands increase with external temperature while water‐oxygen content decreases. The inter‐individual variation in growth rate and mitochondrial function from white muscle and liver of brown trout was measured at 19.5°C or near‐optimal temperature (12°C). At 19.5°C, low phosphorylation efficiency caused increased generation of ROS and decreased ATP production. Differences in mitochondrial phosphorylation efficiency predicted growth rates. Data from this reference were used for Figure 10A,B,D,E.
3. Kerbler et.al., (2019) Cold sensitivity of mitochondrial ATP synthase restricts oxidative phosphorylation in Arabidopsis thaliana. New Phytol. 221:1776–1788 [cf. ref. 69].	Mitochondrial ATP synthase when exposed to cold temperatures restricts oxidative phosphorylation in Arabidopsis thaliana. Arabidopsis thaliana, a small plant from the mustard family, exhibits decreased ability to produce ATP when exposed to cold, which limits the rate of oxidative phosphorylation within the plant cell. Data from this reference were used for Figure 10A.
4. Jarmuszkiewicz et al., (2015) Temperature controls oxidative phosphorylation and reactive oxygen species production through uncoupling in rat skeletal muscle mitochondria. Free Radical Biology and Medicine 83: 12–20 [cf. ref. 70].	Investigates how temperature influences oxidative phosphorylation and the generation of reactive oxygen species (ROS) within the mitochondria of rat skeletal muscle. The findings indicate that temperature regulation occurs primarily through oxidative phosphorylation uncoupling. Data from this reference were used for Figure 10A.
5. García‐Díaz et al. (2023) Plasticity of mitochondrial function safeguards phosphorylating respiration during in vitro simulation of rest‐phase hypothermia. FASEB J. 37: e22854 [cf. ref. 70]. OK/RBR	The findings indicate that body temperature is downregulated to save energy when resting due to rest‐phase hypothermia. In the hypothermic state, the rate of cellular respiration may decrease. However, hypothermia is also associated with a reduction in proton leakage. Even though the respiration rate may be reduced, there is adaption through mechanisms such as adjusting proton leak. Such plasticity of leak respiration may safeguard ATP production during periods of lowered body temperature. Data from this reference were used for Figure 10B,D,E. Data were also taken from Dr. García‐Díaz's Ph.D. thesis which may be obtained upon request.
6. Ton et al. (2021) Effects of heat waves during postnatal development on mitochondrial and whole‐body physiology: An experimental study in zebra finches. Front Physiol. 12:661670 [cf. ref.71].	The effects of heat waves on whole‐body metabolism were measured at the cellular and whole‐organism levels using Zebra finches exposed to heat for 18 days after hatching. Body mass, growth, the metabolic rate, temperature, and the relative water economy were measured at three ages corresponding to ectothermic (day 5), poikilothermic (day 12), and homoeothermic (day 50) stages. Early‐life exposure to heat did not impact whole‐body metabolic and hygric physiology. Body temperature was lower for heated birds, and mitochondria from heated birds had higher endogenous and proton‐leak‐related respiration, although oxidative phosphorylation, maximum respiratory capacity, and coupling efficiency were not impacted. The results suggest that early‐life exposure to high ambient temperature induces programming effects on cellular‐level and thermal physiology that may not be apparent for whole‐animal metabolism.

FIGURE 10.

The influence of temperature on oxygen consumption. For each figure, the temperature change represents the change in ^oC from an ambient temperature of ~25°C, with the respective linear regression and 95% confidence limits for each figure. Data from references68, 69, 70, 71, 72, 73, 74 were used to develop the relationships. For (A), data for oxygen consumption was derived using data obtained from various sources (e.g., polar and Atlantic cod, ⁶⁷ muscle and liver cells from brown trout, ⁶⁸ the Columbian plant‐ Arabidopsis thaliana, ⁶⁹ and skeletal muscle from the rat). Succinate was used as substrate. For (B), the effect of temperature on proton leak is examined. Mitochondrial complex II activity was derived from data using whole blood samples from Parus Major a small passerine bird in the tit family Paridae ⁷⁰ and muscle and liver tissue from brown trout. Oxygen consumption was measured with or without the addition of oligomycin, and the leak state was determined by subtracting basal respiration. The data represent the ratio of leak state at experimental temperatures relative to basal temperature. The proton leak increased with rising external temperature. (C) The oxygen consumption rates were also measured following the addition of FCCP (cyanide‐4‐(trifluoromethoxy) phenylhydrazone. ⁷⁰ FCCP (cyanide‐4‐(trifluoromethoxy) phenylhydrazone) is a protonophoric uncoupler that initiates proton leakage by uncoupling protein 1 (UCP1) in brown fat and ADP/ATP carrier (AAC) in other tissues. Uncoupling was measured using the same tissue sources as described in (B). When oxygen consumption data were compared after FCCP addition, the relative ATP production efficiency decreased as temperature increased (D). A bell curve was obtained in response to changing temperature, suggesting optimal electron chain functionality within a temperature range of ~ +/− seven degrees. Moreover, when oxygen consumption data were compared before and after inhibitor additions, the relative ATP production efficiency decreased as temperature increased (E).

Moreover, the complex II‐linked electron system was also assessed using data in which FCCP (carbonyl cyanide‐p‐trifluoromethoxy phenylhydrazone) was used as an ATP production inhibitor. FCCP is an ionophore that disrupts ATP synthesis by transporting hydrogen ions through the mitochondrial membrane before they can be used for oxidative phosphorylation. The oxygen consumption rates followed a bell curve in response to temperature changes. That is, cells become less efficient at converting energy into ATP at higher temperatures (Figure 10C). Such assessments indicate mitochondrial membranes are compromised when temperature increases, which leads to decreased relative ATP production efficiency (Figure 10D).

Although the increase in the core temperature in response to excessive external temperature may be influenced by factors such as exposure duration, humidity, physical activity, dilation of blood vessels, and insulation, a general estimate can be provided based on physiological principles. On a humid day with a temperature of 102°F, it takes as little as one or 2 h for a person's core temperature to rise from normal (98.6°F) to 100°F. If doing work, the energy from physical activity would add to and generate additional internal heat. When there is minimal sweating or evaporation, the rate of heat absorbed from the surface area (e.g., ~two square meters) of a human exposed to 100°F is approximately 67.2 watts or ~ 60kCal/hour. Two hours of heat exposure a day could generate up to a pound of fat in a 30‐day month. Additional observations that address elevations in body core temperature and thermogenic regulation effects on hormone and signaling molecules are summarized in Table 2. Moreover, such estimates are in keeping with those of Kanazawa, ⁷⁵ who suggests that external temperature can have as much effect on BMI as age and more than most exercises on an annual basis. For example, Kanazawa notes that moving from Phoenix, AZ, to 150 miles north to Flagstaff might reduce weight by 5 lbs. or more per year. For reference, Phoenix, AZ, in 2023 had 111 days per year at or above 100 degrees; Flagstaff had none.

TABLE 2.

Elevations in body core temperature and thermogenic regulation: effects on hormone and signaling molecules, and mitochondrial uncoupling.

Source	Description
1. Kaiyala et al. (2015). Leptin signalling is required for adaptive changes in food intake, but not energy expenditure, in response to different thermal conditions. PloS One, 10: e0119391. [cf. ref. 76].	Prolonged exposure to heat may reduce leptin sensitivity, potentially leading to increased food intake and reduced energy expenditure. The disruptions in leptin signaling can be associated with weight gain.
2. Ataallahi et al. (2024). Assessment of Heat Processing Effects on Cortisol Concentration in Dairy Milk Products. Food science of animal resources, 44: 1453–1461. [cf. ref. 76].	Changes in environmental temperature may affect ghrelin secretion, potentially increasing hunger. Dehydration from heat exposure can also indirectly impact ghrelin levels.
3. Kim et al. (2022). Heat Stress during Summer Attenuates Expression of the Hypothalamic Kisspeptin, an Upstream Regulator of the Hypothalamic–Pituitary‐Gonadal Axis, in Domestic Sows. Animals: 12: 2967. [cf. ref. 77]	Heat stress can activate the hypothalamic–pituitary–adrenal (HPA) axis, increasing cortisol secretion. Elevated cortisol levels promote fat accumulation.
4. Winn et al. (2024) Insulin at the intersection of thermoregulation and glucose homeostasis. Molecular Metabolism 81:101901. [cf. ref. 78].	Heat stress may cause insulin resistance, leading to hyperinsulinemia, which promotes fat storage and obesity. In addition to adaptations in insulin action, ‘insulin‐independent’ glucose uptake in brown fat is sensitive to thermoregulation. Insulin action adjusts to non‐stressful changes in ambient temperature to support body temperature homeostasis without compromising glucose homeostasis.
5. Iwen et al. (2018) Effects of thyroid hormones on thermogenesis and energy partitioning. Journal of molecular endocrinology, 60: R157–R170. [cf. ref. 79].	Prolonged heat exposure can suppress thyroid hormone (T3 and T4) activity, reduce metabolic rate, and contribute to weight gain. Thyroid hormone levels adjust to hot environments by lowering the metabolic rate to help regulate core temperature.
6. Laursen et al. (2018) Leptin, adiponectin, and ghrelin responses to endurance exercise in different ambient conditions. Temperature 4: 166–175. [cf. ref. 80].	The ability to alter the appetite‐regulating hormones leptin, adiponectin, and ghrelin may help in decreasing excessive energy intake. Exercise and exposure to extreme temperatures can independently affect these appetite‐regulating hormones.
7. Harding et al. (2017) The Temperature Dependence of Sleep. Frontiers in neuroscience, 13: 336 [cf. ref. 81].	Melatonin regulates circadian rhythms and metabolic processes, particularly during sleep. Heat‐related sleep disturbances can reduce melatonin levels, disrupting metabolism and promoting weight gain.
8. Zhang et.al. (2021). The Effects of Estrogens on Neural Circuits That Control Temperature. Endocrinology, 162: bqab087 [cf. ref. 82].	Estrogen is crucial in regulating thermogenesis by facilitating heat production management and dissipation. Its effects on thermogenic regulation are particularly relevant in warm environments, where maintaining thermal homeostasis is vital.
9. Morrison, S. F., & Nakamura, K. (2019) Central mechanisms for thermoregulation. Annual Review of Physiology 81: 285–308 [cf. ref. 83].	Summarizes the neural mechanisms that regulate body temperature. It highlights the role of the central nervous system, particularly the hypothalamus, in coordinating responses to maintain homeostasis. The review emphasizes how the thermoregulatory system adapts to prolonged environmental challenges (e.g., cold acclimation) and becomes dysregulated in pathological conditions like fever or hypothermia.
10. McKenna et al. (2024) Plasma epinephrine and norepinephrine responses to extreme heat exposures in young and older adults. American journal of physiology. Regulatory, integrative and comparative physiology, 327: R188–R194. [cf. ref. 84].	Epinephrine and norepinephrine promote non‐shivering thermogenesis, especially in brown adipose tissue, during cold exposure. Exposure to cold environments stimulates the sympathetic nervous system, leading to increased release of norepinephrine from sympathetic nerve endings. This elevation in norepinephrine is a primary driver of non‐shivering thermogenesis, particularly in brown adipose tissue. In contrast, during heat stress, heat convection is facilitated. Norepinephrine is decreased, and vasodilation and increased blood flow to the skin occur for conductive heat loss.
11. Sladek, C. D., & Johnson, A. K. (2013). Integration of thermal and osmotic regulation of water homeostasis: the role of TRPV channels. American journal of physiology. Regulatory, integrative and comparative physiology, 305: R669–R678. [cf. ref. 85].	Maintaining body water homeostasis is critical for preventing hyperthermia, because evaporative cooling is the most efficient means of dissipating excess body heat. Water homeostasis is achieved by regulating water intake and water loss by the kidneys. The former is achieved by sensations of thirst that motivate water acquisition, whereas the antidiuretic action of vasopressin regulates the latter. Vasopressin secretion and thirst are stimulated by increases in the osmolality of the extracellular fluid as well as decreases in blood pressure and blood volume, signals precipitated by water depletion associated with the excess evaporative water loss required to prevent hyperthermia. In addition, they are stimulated by increases in body temperature. The sites and molecular mechanisms involved in integrating thermal and osmotic regulation of thirst and vasopressin secretion are reviewed here, focusing on the role of the thermal and mechanosensitive transient receptor potential‐vanilloid (TRPV) family of ion channels.
12. Ruocco et al. (2023). Amino acids contribute to adaptive thermogenesis. New insights into the mechanisms of action of recent drugs for metabolic disorders are emerging. Pharmacological research. 195: 106892. [cf. ref. 86].	This paper explores the role of amino acids in adaptive thermogenesis, a physiological process that contributes to energy expenditure and metabolic regulation. Recent advances in understanding the mechanisms of action of how amino acids influence pathways related to thermogenesis are discussed, underscoring the importance of amino acids in energy homeostasis. Evidence is also provided supporting that the dual and triple agonists of glucagon‐like peptide‐1 (GLP‐1) and the glucagon (GCG) receptor promote thermogenic‐like amino acid profiles in BAT with increased heat production.

5. SIGNIFICANCE AND CONCLUSION

The implications of global warming on public health are alarming. When external temperatures surpass the body's ability to maintain thermogenesis in many organisms, it can lead to lethal behavioral maladaptation. The number of people displaced worldwide due to global warming reached a staggering high, exceeding 100 million in 2022, over one percent of the current world population. This number is projected to increase by ten percent over the next two decades (cf., UNHCR Global Trends Reports, 2023, https://www.unhcr.org/mid‐year‐trends). In the Southwestern regions of the United States, approximately sixty percent of the 538 plants and animals examined may face extinction in the next 50 years. Worldwide, it is currently estimated that roughly half of the world's 4000 species of non‐domesticated animals are moving, with many migrating northwards towards higher latitudes.^{89, 90, 91}

The Industrial Age began 80 years before the first signs of rising sea temperatures. The ocean and land‐air temperatures were in sync until the late twentieth century, after which global mean surface temperatures (GMST) began to rise at nearly double the rate of surface ocean water. GMSTs are now approximately 2°C above preindustrial levels, and predictions indicate they may exceed 2.5°C by 2035,^{89, 90, 91} a crisis with grave public health consequences and challenges. For instance, a 1°C increase in temperature in developing countries is associated with a significant increase in children's BMI ⁶⁶ and poor productivity. ⁹² This alarming climate change‐obesity relationship raises food security concerns and comes with societal costs that are not easily accommodated in a world influenced by significant authoritarian thinking. These findings underscore the urgent need for action to mitigate the effects of global warming on public health.

Nutritionists and dietitians must consider nutritional requirements beyond the conventional diet and activity criteria, acknowledging the importance of scaling energetic needs to metabolic body size and not simply body weight. The current situation demands a more comprehensive approach that includes thermogenic and physical‐based concepts that involve more than just the free energy of ATP utilization.^{93, 94, 95} The flux of nutrients and heat is an entropic process in keeping with the laws of thermodynamics. Importantly, in regions where the external temperature exceeds the body's normal thermal neutral zone, solar heat can result in caloric excesses. As Kanazawa has noted, ⁷⁵ in the context of obesity, global warming can have as much effect on BMI as age and exercise. Changes in core temperature can have profound changes in behavioral and metabolic regulation, such as the hormone examples in Table 2. All are consistent with the biological mechanisms presented herein, that is, changes in ambient global temperatures affect thermogenic regulation and ATP production efficiency, which potentially contribute to adipose deposition and increases in obesity.

AUTHOR CONTRIBUTIONS

Imani Muhammad acquired data and background material and played a crucial role in the analysis and interpretation of data. Francene Steinberg and Jennifer Larsen were involved in revisions of the manuscript. Dr. Steinberg focused on various syndemic relationships as a driver of heat regulation and potential negative impacts on health. Dr. Larsen focused on sections relevant to heat regulation. Robert B. Rucker developed the sections dealing with allometry and body heat regulation.

FUNDING INFORMATION

USDA CA‐D‐NTR‐6316‐H (to FS), and a grant from the UCD Emeriti Association (to RBR).

CONFLICT OF INTEREST STATEMENT

All authors declare no conflicts of interest.

Muhammad I, Steinberg F, Larsen J, Rucker RB. Global warming and obesity: External heat exposure as a modulator of energy balance. FASEB BioAdvances. 2025;7:e1487. doi: 10.1096/fba.2024-00140

DATA AVAILABILITY STATEMENT

The data are available on request or from the cited corresponding author.