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. 2021 Aug 17;33(4):264–268. doi: 10.1089/acu.2020.1500

The Role of Electroacupuncture in the Regulation of Appetite-Controlling Hormone and Inflammatory Response in Obesity

Dinda Aniela Bintoro 1,✉, Irma Nareswari 1
PMCID: PMC8403175  PMID: 34471444

Abstract

Objective: Obesity, a condition with serious complications, needs special attention. It is a complex and multifactorial problem and regulation of calorie balance involving various humoral and central factors is the main key for managing obesity. In addition, there is an increase in various proinflammatory cytokines and an increase in oxidative stress. There is a need to discover a useful therapy for obesity management. The goal of this review was to examine the literature on electroacupuncture (EA) as a potential therapy.

Methods: This review explores the literature on EA, which has proven to be effective for inducing weight loss in experimental human and animal studies. Both continuous and dense-disperse EA waves have their own roles in hormone regulation of obesity using ST 25, CV 9, CV 12, CV 4, SP 6, ST 36, and ST 44; this is discussed the associated mechanism related to this is through suppression of various orexigenic peptides, enhancement of anorexigenic peptides, suppression of inflammatory factors, and improvement in the balance of pro-oxidants and antioxidants.

Conclusions: The absence of another definitive therapy for obesity and EA's minimal side-effects make it a potential therapy for managing obesity.

Keywords: electroacupuncture, obesity, inflammation, oxidative stress

Introduction

Obesity is a complex and multifactorial problem. The increased prevalence of obesity globally has caused increased morbidity and mortality rates. There are approximately 1 billion adults who are overweight and 475 million of these adults are obese worldwide.1 It is estimated that, by 2030, 38% of the world's population will be overweight, and 20% will be obese.2 This should be a concern, because obesity is associated with an increased risk of noncommunicable diseases, and causes economic and psychologic burdens on the overall health system.3

The main key to the management of obesity is to reduce calorie intake and increase calorie output. Presently, pharmacologic and nonpharmacologic approaches have not yet achieved satisfactory results and have caused various side-effects.4 Other therapeutic modalities are continually being sought to improve obesity management; acupuncture is a relatively safe therapeutic option with minimal side-effects. It has been proven effective to treat a variety of endocrine diseases and disorders, including obesity. In a review, by Lacey et al., in 2003, 4 of 7 clinical trials using both ear acupuncture and body acupuncture reduced body weight and fat levels, compared to a control group.5 Some animal experiments have shown that acupuncture can decrease appetite through regulation of the central feeding regulator in the hypothalamus.6

A systematic review by Wang et al., in 2019, discussed the potential molecular mechanism for acupuncture in obesity.7 Wang demonstrated the role of electroacupuncture (EA) in the regulation of appetite, modulation of inflammatory responses, and improving conditions of oxidative stress.7 EA has the advantage of setting stimulation frequency and intensity objectively and quantifiably.8 Therefore, this review discusses the role of EA as an obesity therapy option in terms of biomolecular aspects of appetite-hormone regulation, the inflammatory response, and its relation to oxidative stress.

Obesity

Obesity is condition of abnormality or excess fat accumulation in adipose tissue that is a risk to health.9 Obesity occurs if, in a period of time, more kcals enter through food than are used to support the body's energy requirements.2 Obesity is classified based on the body mass index (BMI) value in which body weight in kg, divided by height in meters squared.10 Obesity classification, according to the World Health Organisation (WHO) Asia Pacific, is divided into underweight, normal range, overweight, risky, obese I, and obese II.11

Pathophysiology of Obesity

Obesity is caused by an imbalance in energy use and food intake as well as complex interactions among genetic and environmental factors. This affects metabolic, neurohormonal, and hemodynamic regulation and causes inflammation, toxicity, apoptosis, and oxidative stress. The center for regulating food intake is located in the hypothalamic arcuate nucleus (ARC) and, in general, there are 3 physiologic processes, namely:

  • (1)

    the afferent system produces humoral signals from adipose tissue (leptin), pancreas (insulin), and stomach (ghrelin)

  • (2)

    central processing units, especially in the hypothalamus, which are integrated with afferent signals

  • (3)

    the effector system carries orders from the hypothalamus nucleus in the form of reactions to eating and energy expenditure.

There are 2 groups of genes that affect obesity: (1) orexigenic or anabolic (neuropeptide Y; NPY with agouti-related proteins; [AgRP]); and (2) anorexigenic or catabolic genes (pro-opiomelanocortin; POMCs and transcription, which is regulated by cocaine and amphetamine [CART]).12

If the energy intake exceeds the required amount, then the adipose tissue increases accompanied by an increase in blood levels of leptin. Leptin then stimulates the anorexigenic center in the hypothalamus to reduce NPY production, resulting in decreased appetite. Vice versa, if the energy needs are greater than energy intake, the adipose tissue decreases and stimulation occurs in the orexigenic center in the hypothalamus, which, in turn, causes an increase in appetite. In most people with obesity, leptin resistance occurs, so that high levels of leptin do not cause a decrease in appetite.13

Acupuncture in Obesity

Within the last 2 decades, there have been many kinds of research on obesity that show acupuncture's role in weight loss achieved through central and peripheral mechanisms.5 In the central or neural system, acupuncture plays a role in regulating at the hypothalamus level, namely, regulation of 2 groups of orexigenic and anorexigenic peptides, while the effect on the peripheral or humoral system is through regulation of the leptin, insulin, and ghrelin hormones related to food intake.

In the local mechanism, acupuncture at ST 36 Zusanli with 2 Hz of electrical stimulation for 30 minutes causes release of 2 important neurotransmitters involved in weight loss, namely serotonin and β-endorphins.14 Acupuncture needling causes an increase in β-endorphin levels in plasma and in the central nervous system (CNS), which, in turn, increases lipolysis activity.15 Stimulation of acupuncture at ST 36, GV 20 Baihui, Ex-HN 3 Yintang, and BL 23 Senshu also causes an increase in serotonin (5-hydroxytryptamine) levels in the CNS.16–18 Serotonin stimulation causes a decrease in food intake and body weight and increases energy use.19 NPY is one of the orexigenic genes that is influenced by serotonin.20

The central mechanism of acupuncture in obesity is achieved by regulation of the central appetite in the hypothalamus so that it can reduce food intake and increase energy use; this has been proven in experimental studies in animals and in humans.7

Ea in Obesity

EA for Regulating Appetite-Controlling Hormone

The center of appetite regulation is dominated by a complex circuit in the ARC and is influenced by afferent signals from adipose tissue (leptin), pancreas (insulin), and stomach (ghrelin).21 In addition, food intake is also influenced by neurons originating from 2 different sources, namely orexigenic and anorexigenic peptides.

Research conducted by Gong et al., in 2012, in mice with simplex obesity produced an increase in leptin expression and decreased expression of leptin receptors that are known to be a cause of impaired leptin response in conditions of leptin resistance.22 In animal models, EA at ST 36 and ST 44 Neiting, using a 10-Hz continuous wave can increase the bonds among the hormone leptin, insulin, and its receptors in the hypothalamic ARC.22 This is in line with the study of Darbandi et al. using EA 30–40-Hz dense disperse (DD waves), which showed the positive effect of EA in decreasing plasma leptin levels that were thought to be due to a decrease in body-fat levels.23

Ghrelin is a peptide produced by the stomach and plays a role in stimulating AgRP and NPY. Ghrelin increased in obese mice that were fasted for 16 hours.24 EA at ST 36 and SP 6 Sanyinjiao using continuous wave at 2 Hz for 30 minutes reduced the mice's food intake significantly, compared to mice in a control group (9.6 ± 0.3 g versus 11.4 ± 0.4 g; P < 0.05).25

In regulation of neurons in the hypothalamus, 2-Hz continuous-wave EA caused a decrease in NPY mRNA levels significantly, compared to those of a control group (0.87 ± 0.03 versus 1.00 ± 0.02; P < 0.05).25 Another study showed that EA continuous wave at 2 Hz and at 100 Hz applied to ST 36 and SP 6 for 30 minutes increased levels of anorexia peptide CART and alpha-melanocyte-stimulating hormone (α-MSH) in the hypothalamus, with an increase of CART in the 2-Hz EA group higher than in the 100 Hz EA group, compared to the control group (P < 0.001 and P < 0.05, respectively).26,27 The increase of anorexigenic peptide and decrease of orexigenic peptide contribute to the role of EA in losing weight.

EA for Modulating of Obesity Inflammatory Response

Obesity is a low-grade inflammatory condition characterized by increased levels of leptin, decreased levels of adiponectin in the circulation, and an increase in the number of activated macrophages in white adipose tissue (WAT).28 Additionally, in obesity, there is a mild increase in proinflammatory factors—such as interleukin (IL)–6 and tumor-necrosis factor-alpha (TNF-α)—without clinical signs so that it is referred to as a subclinical inflammation.29

EA has a regulatory role in influencing various proinflammatory and anti-inflammatory cytokines. Seven days of 10-Hz continuous-wave EA at ST 36 for 20 minutes in obese-model rats decreased the number of macrophages and also increased obesity-associated factors of sterol regulatory element-binding protein-1 (SREBP-1) and expression of target genes in obese model mice.30 EA also lowered F4/80 and CD11b macrophages in the epididymis of adipose tissue. In addition, there was a decrease in TNF-α, IL-6, monocyte chemotactic protein-1 (MCP-1), and expression of CD68 mRNA in adipose tissues of obese model mice, as well as a decrease in serum TNF-α, IL-6, and IL-1 levels. MCP-1 is an important chemokine that plays a role in leukocyte migration, so MCP-1 reduction causes a reduction in the inflammatory process, while CD11b is a proinflammatory cytokine that increases in cases of obesity.30

EA has produced different effects on 2 different obesity models. EA at CV 12 Zhongwan and CV 4 Guanyuan with a 10-Hz continuous wave in experimental animals with metabolic syndrome models produced a significant reduction in TNF-α and an increase in the IL-10:TNF-α ratio, while, in a simplex obesity model, EA produced a significant increase in leptin and a decreased adiponectin:leptin ratio.31

EA in Oxidative Stress

There is an increase in levels of pro-oxidant antioxidant balance (PAB) that is positively correlated with weight gain in obesity.32 This excess reactive oxygen species (ROS) is caused by decreased antioxidants, such as catalase, glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), which contribute to inflammation and apoptosis.

EA at ST 25 Tianshu and GB 28 Weidao, along with manual acupuncture at several other points, with 30–40 Hz DD waves produced a significant decrease in PAB in a treatment group, compared to a sham EA group, and this difference persisted for 12 weeks.33 This is in line with research conducted by Yu et al., in 2010, who examined the effects of acupuncture in Parkinson's rats who experienced neuronal degeneration due to exposure to ROS. The EA-treated rats had decreases in SOD, GSH-Px, and GSH.34

This improvement shows the antioxidant and neuroprotective role of acupuncture. This mechanism is thought to work through the effect of acupuncture that works according to the afferent pathway and causes various neurologic and physiologic changes, one of which is an antioxidant-defense mechanism. Acupuncture can play a role in neuromodulation of input to the CNS, and play a role in the effects of antioxidants, as well as increasing blood flow, which can support oxygenation and glucose supply to inhibit increased ROS production.34,35

Discussion

Obesity is a complex problem due to an imbalance between calorie intake and expenditure, as well as the interaction with genetic and environmental factors.2 As the prevalence of obesity increases globally, comprehensive obesity management is needed. Until now, management of obesity has not been satisfactory, so that other therapeutic modalities are being sought continually, and acupuncture is 1 therapeutic option.4 EA as an acupuncture modality that has measurable and clear parameters has proven to be effective for reducing weight in obese patients.23

In obesity, there is an increase in leptin expression, decreased expression of leptin receptors, and an increase in ghrelin.24,26 Research also shows a decrease in anorexigenic neurons POMC and CART, as well as an increase in orexigenic peptide NPY.23,36 In addition, an increase in adipose tissue that occurs in obese patients causes increased macrophages as well as various proinflammatory cytokines and a decrease in anti-inflammatory cytokines.29 An imbalance between pro-oxidant and antioxidant (PAB) levels is also known to contribute to the inflammation that occurs in obese patients.33

Research shows that EA is effective for decreasing plasma leptin levels, increasing binding between leptin and its receptors, decreasing ghrelin, increasing anorexigenic CART and α-MSH peptides, and decreasing NPY.22,23,25–27 In addition, EA is also effective for decreasing macrophages, TNF-α, IL-6, MCP-1, IL-1 serum; increasing IL-10; and maintaining the balance of PAB through its role in decreasing ROS.30,33

Various choices of points, frequencies, durations, and wave types are used to manage obesity. The most commonly used acupuncture points are ST 25, CV 9, CV 12, CV 4, SP 6, ST 36, and ST 44.23,25,26,30,33,37–39 The mechanism of action of acupuncture at these points is related to the regulation of appetite that works from the peripheral level to the regulation of the orexigenic or anorexigenic peptides in the hypothalamus. Acupuncture also plays a role in increasing serotonin, which causes a decrease in NPY and β-endorphins to increase lipolysis activity. The duration of therapy ranges from 20 to 40 minutes for 1 treatment, with an average frequency of therapy 2–3 times per week with a total therapy that varies greatly between 6 and 12 times per week.23,26,30

Two-Hz continuous-wave EA is effective for reducing NPY mRNA peptides in the hypothalamus dan gastric ghrelin levels, while a 10-Hz frequency is effective for reducing serum leptin levels, increasing leptin-receptor binding on the hypothalamus, and reducing various proinflammatory cytokines.25,30,38,39 Continuous-wave 2-Hz EA causes a decrease in food intake and body weight >100 Hz, but 100 Hz is superior in increasing levels of CART, an anorexigenic peptide in the hypothalamus.26 EA at a 30–40-Hz DD wave was effective for inducing weight loss, reducing BMI and serum PAB levels significantly in a treatment group, compared to a control group (P < 0.001).33 Weight loss that occurred with use of a 2-Hz continuous wave had almost the same effectiveness as a 30–40 Hz DD wave (3.32% and 3.15%, respectively), although there were different points used in these 2 studies.23,26

EA produced different effects in 2 different models of obesity, namely simplex obesity and obesity in metabolic syndrome. These different effects are thought to be due to the release of various proinflammatory cytokines in metabolic syndrome so that the anti-inflammatory effects of the 10-Hz continuous-wave EA that occurred in this group were more visible than the simplex obesity group.40

In simplex obesity, 2-Hz continuous-wave EA is effective in regulation at the central level, with an increase in CART and α-MSH anorexigenic peptides—an increase in NPY and ghrelin orexigenic peptides results in decreased food intake. Ten Hz plays a role in leptin-hormone regulation, while 100 Hz causes an increase in peptide anorexigenic CART and α-MSH. Use of 30–40 Hz DD waves EA is also effective for reducing leptin levels and decreasing serum PAB levels. Both types of waves—both continuous low- and high-frequency, and DD waves—have their respective roles in obese patients, and use of DD waves is considered more beneficial to produce low- and high-frequency effects.41

Conclusions

The effectiveness of EA in cases of obesity with various points, frequencies, durations, and waves has been proven in various studies conducted on animals and humans. With these results, EA can be a therapeutic choice for addressing obesity to achieve more-optimal results with minimal side-effects.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

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