In this issue of Adipocyte

Brown Adipocyte and Body Weight Regulation, pp. 196–200

Although its thermoregulatory properties are well known in small rodents, brown adipose tissue (BAT) and its roll in adult humans has only recently entered the debate. In this mini-review by Lockie, Stefandidis, Oldfield, and Perez-Tilve, the authors explore the scientific community’s current thoughts on BAT regulation and its ties to the central and sympathetic nervous system. As the authors have noted in previous research, several peptides have been shown to induce BAT thermogenesis, which could lead to therapies targeting not only weight loss, but type 2 diabetes as well.

Sleeping at the Right Time May Be More Important Than You Think, pp. 201–6

In this mini-review by Shostak, Husse, and Oster, the authors explore the link between various states of adipose function and how they may be linked or even regulated by our very own circadian clock. Having both an active phase where nutrients are transported and an inactive phase where nutrients are released as free fatty acids, adipose tissue and its phases may be coordinated and controlled by circadian clocks. This means that in our “24/7 society”, not only does the disruption of our circadian rhythm make us tired and groggy, but it may also have an effect on metabolism, lipid breakdown, adipokine function, lipogenesis regulation, and other adipose functions.

Menin Expression and CoPP, pp. 207–16

Oxidative stress (an increase in reactive oxygen species, or ROS) has been shown to decrease vascular function, as well as increase inflammatory cytokines and promote adipocyte hypertrophy. Recent findings have shown that menin plays a part in regulating oxidative stress. In this research paper, authors Angevine, Wuescher, and Mensah-Osman look into how interactions between adipocytes and endothelial cells regulate adipogenesis by a change in cobalt protoporphyrin IX (CoPP)-mediated menin expression. Their findings show that conditioned media from CoPP-treated endothelial cells can be associated with a loss of menin expression, as well as increased adipogenesis (Fig. 1).

Figure 1. Figure detail from Angevine et al., p. 213

Adiponectin and Adipose Tissue Expansion, pp. 217–26

In obese individuals, a variation in fat cell size is thought to have an impact on adipose tissue function, as a nutrient excess can lead to an increase in fat cell size and number. Additionally, research has shown that while weight loss leads to a reduction in fat cell size, it also results in an increase of adiponectin. In this research paper from Meyer et al., the authors shed light on the relationship between adipose tissue (AT) expansion and regional distribution and its contribution to levels of adiponectin. Although the actual regulation of adiponectin is still uncertain, the results of this study show that decreased levels of adiponectin in obesity are influenced by differences in fat cell size and regional AT distribution.

A Potential Gift from the Brazilian Honeybee, pp. 227–36

Recognized in Brazil as an effective medical substance, the Brazilian honeybee hive product propolis has been shown to have anti-inflammatory, anti-tumor, anti-oxidative, and microbicidal effects. There is also research indicating a possible effect on energy metabolism. Authors Kitamura et al. dive deeper into the anti-diabetic effects of Brazilian propolis in this research paper by examining the impact of the substance on ob/ob mice. Treated mice exhibited improved glucose homeostasis and lower weight gain in mesenteric adipose tissue, an increase in eosinophils, as well as a reduction in adipose proinflammatory macrophages. Overall, the research presented here supports the idea that Brazilian propolis can indeed improve diabetes in ob/ob mice (Fig. 2).

Figure 2. Figure detail from Kitamura et al., p. 233

Start Them Young, pp. 237–45

How early can adipose tissue gene expression be influenced by diet? In this brief report by MacKay et al., maternal diet during the lactational period is examined in rats in order to learn more about the adipose tissue response to calorie intake in the offspring. It is known that mothers who are fed a diet high in fat during pregnancy and nursing in turn have offspring that are heavier and more prone to weight gain. Here, the authors took a different approach by introducing a 50% food restriction treatment as well as a standard and high fat diet. Mothers were given one of the three diets and the results showed that while all offspring maintained similar body weights, those subjected to high fat diets had an increased body fat percentage as well as changes in the adipose genes regulating fatty acid metabolism.

PPARγ Regulation by ALK7, pp. 246–50

This brief report by Togosawa and Izumi shows that the activin receptor-like kinase 7 (ALK7) signaling pathway inhibits transcription factors that control adipogenesis including CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), in both lean and obese states. Interestingly, in the obese state, PPARγ is further suppressed through an ALK7-independent pathway. The authors discuss the significance of PPARγ reactivation in obesity, and, propose that ALK7 inhibition may be a novel mechanism to enhance PPARγ activation and a potential treatment for obesity and metabolic disorders.

ZBED6 Does Not Regulate Adipogenesis, pp. 251–5

The transcription factor ZBED6 has been shown to affect muscle mass and fat deposits in pigs; however the mechanism that actually mediates fat mass remains unclear. Authors Zhang et al. attempt to determine the effect of ZBED6 mRNA knockdown on preadipocyte differentiation as well as gene expression in pigs. While the study did not find evidence supporting the idea that ZBED6 has a starring role in preadipocyte differentiation or proliferation, the authors note that it may still play a role in fatness through effects on adipocyte hypertrophy.

Protein Modification Regulates Metabolic Function, pp. 256–61

Current research has shown that posttranslational modifications (PTM) of metabolic proteins contribute to glucose homeostasis. In this perspective, Rao Ande et al. summarizes data available on the ubiquitylation, acetylation, and phosphorylation of enzymes involved in glucose metabolism to reveal a large number of PTM modifications that cluster together in key metabolic proteins to regulate their cellular function.

A Potential Treatment through 5-LO, pp. 262–5

With the obesity crisis growing worldwide, an increasing amount of evidence points to the low-grade inflammation caused by obesity and its influence on ailments such as type 2 diabetes and atherosclerosis. This commentary by Neels describes recent findings focused on the role of the enzyme 5-lipoxygenase (5-LO) with regards to the induction and resolution of adipose tissue inflammation. The author discusses how 5-LO and its inflammatory or specialized pro-resolving mediators may be targeted as a viable alternative treatment for insulin resistance and other obesity related conditions brought about by low-grade inflammation.

Galectin-3: a Star Inflammatory Regulator, pp. 266–71

Authors Pejnovic et al. recently showed that galectin-3-deficient mice that were fed a high fat diet displayed proinflammatory changes in visceral adipose tissue as well as pancreatic islets. These mice also showed excesses in adiposity, as well as systematic inflammation, insulin resistance and hyperglycemia all of which were associated with an increase in type 1 T and NKT cells as well as pro-inflammatory CD11c⁺CD11b⁺ macrophages present in the visceral adipose tissue. This may suggest an important role for galectin-3 when it comes to regulating metaflammation and type 2 diabetes.

New Insights on Preadipocyte Proliferation, pp. 272–5

Adipose tissue expansion due to the proliferation and differentiation of preadipocytes results in obesity when an excessive dietary fat intake is introduced. But while research in preadipocyte differentiation is abundant, there is relatively little known about preadipocyte proliferation. Authors Traustadottir et al. discuss the regulation of preadipocyte homeostasis and adipose tissue expansion, suggesting that Delta-like 1 homolog regulates preadipocyte’s entry into G1/S-phase and thus inhibiting preadipocyte proliferation. This insight may open the door to new treatments for obesity down the line (Fig. 3).

Figure 3. Figure from Traustadottir et al., p. 273

γ-Synuclein and Fatty Acid Metabolism, pp. 276–80

γ-synuclein, a neuronal protein, is known to be highly expressed in human white adipose tissue and when obesity is factored in, is increased. Millership et al. previously displayed how γ-synuclein is regulated through nutrition, and how a loss of it actually protects mice from high fat diet-induced obesity as well as other metabolic complications. In this commentary, the authors discuss how their data as well as other findings support claims that γ-synuclein is key in the regulation of lipid handling in adipocytes, while also having an effect on whole body energy expenditure.

An Aid to Our Ancestors May Be a Curse to Us, pp. 281–4

Current studies have revealed ways in which the metabolic interactions between organs are involved in maintaining body weight as well as regulating energy intake and consumption. The discovery of a new interorgan neural network from the liver by authors Yamada et al. can be seen as a step forward in understanding how these interactions work, as described in this commentary. The interorgan neuronal relay system discussed may function by sensing an increase in energy intake and working to suppress energy expenditure, which in turn would protect the body from starvation. While this mechanism may have favored our ancestors during times of food shortages, unfortunately, in the modern day this mechanism may be detrimental, and can push us further and further toward obesity.

Histone Modifiers and Adipogenesis, pp. 285–8

Phf2, a recently identified dimethylated histone H3 lysine 9 demethylase, has been shown in vitro to have an effect on macrophages and hepatocytes. But it is still unclear whether Phf2 retains this significance when in vivo. In this commentary, authors Okuno, Inoue, and Imai discuss how they generated and analyzed Phf2 knockout mice in order to determine that Phf2 has a positive role in adipogenesis. Additionally, the authors note remaining questions stemming from their study and stress the importance of understanding the exact role that histone modifiers play with regards to adipocytes and their involvement in obesity and metabolic syndrome (Fig. 4).

Figure 4. Figure from Okuno et al., p. 287

Irisin under a New Light, pp. 289–93

Discussing the original 2002 discovery and characterization of fibronectin domain-containing (protein) 5 (FNDC5) under the lens of the 2012 discovery of irisin, a proposed skeletal muscle exercise hormone derived from FNDC5, Erikson notes three problems with the characterization of irisin. In this commentary, the author brings to light new insights with regards to the antibodies used to detect irisin, the recombinant protein used to detect activity in cell culture, and lack of quantitation of shed irisin relative to membrane FNDC5. When combined, the author brings up the important question, in the presence of these three unresolved issues, do we really know what irisin is after all?