Hunger Signaling: Can It Be Regulated to Treat Obesity?




Recent research suggests that obesity can be controlled by regulating the satiety cascade, including influencing the nerves carrying hunger signals.

Global obesity levels have almost doubled in the last 30 years. This is a worrying fact, especially when considering that obesity represents one of the major risk factors for many chronic diseases, cardiovascular and metabolic diseases in particular. Thus, it is not surprising that conditions like insulin resistance, pre-diabetes, and diabetes are becoming increasingly common worldwide.

Although it is clear that obesity develops when caloric energy intake exceeds energy expenditure, it is not always easy to combat the excessive body weight and fat accumulation. Multiple strategies for tackling obesity and food intake have been developed. These include behavioral (including dietary) changes, interventions with multiple supplements, and pharmacological and surgical treatments.

The latest research-supported developments include controlling obesity by regulating the satiety cascade by influencing the nerves carrying hunger signals. Hunger is a neural signal that initiates eating. Hunger signals originate in the stomach. Furthermore, gut hormones transfer information from the gastrointestinal tract to the centers of appetite regulation located in the central nervous system. This communication between the gut and the brain is known as the gut-brain axis.

It is assumed that information from the gut can be transferred to the brain via both nerve signaling or blood circulation. The hypothalamus has been identified as a key part of the brain in controlling our eating behavior. It integrates peripheral signals that carry information about dietary intake as well as information about energy expenditure.

The hypothalamus receives appetite signals and reacts by modulating the release of neuropeptides in two neuronal populations. While one population of neurons co-express neuropeptides that stimulate appetite and increase hunger (and thus promote eating and weight gain), the other population acts via neuropeptides that decrease appetite (and reduce eating and promote weight loss). Consequently, the balance between these two neuronal populations is essential for the maintenance of optimal body weight.

Considering the importance of the gut-brain axis, influencing the hormones and neurons that carry hunger signals could be a good strategy for obesity control. Drugs that act via hunger-regulating hormones are often prescribed in order to control obesity and body weight, even though they do not appear to be particularly effective in the long term. Meanwhile, the development of strategies that act on neurons and neural signaling is still in the early stages.

One very recent pilot study demonstrated that the freezing of neurons that carry the hunger signals could be an efficient weight loss approach in subjects with mild to moderate obesity. Ten subjects with body mass index (BMI) ranging between 30 and 37 kg/m2 included in this investigation underwent an innovative procedure. Namely, a radiologist inserted a needle through the patients back and used argon gas to freeze the nerve (the posterior vagal trunk) that transfers hunger signals from the gut to the brain. The procedure was done using live images from the CT scan.

After the treatment, the patients were followed for three months. Interestingly, all subjects reported decreased appetite, accompanied by lower BMI and significant weight loss. Specifically, only one week after the procedure the average weight loss was 1%, while after three months it was 3.6%. In addition, at the three-month follow up a 13% decline in BMI was recorded. More importantly, there were no adverse effects or undesired complications for any of the participants involved. The aim of this pilot project was not to shut down the biological response to hunger, but rather to control the hunger signals and reduce their strength. Judging by the first results, it seems that the procedure could represent a useful strategy in reducing excess weight gain through the control of appetite and food intake.

The role of the vagus nerve in the regulation of appetite has been studied previously. Electrical stimulation of the vagus nerve has been identified as clinically relevant for mood regulation, i.e., in the treatment of patients not responding to anti-depressant drugs. On the other hand, stimulation of the vagus nerve for the purpose of obesity treatment has gained attention only recently. Studies in animal models have shown that long-term vagus nerve stimulation could prevent further weight gain by decreasing food consumption. Still, the mechanisms involved are still unclear and further research is required.

Apart from stimulating the vagus nerve, studies have also questioned the effects of vagus blockage (i.e., cutting the vagus nerve) on obesity control. The findings from these studies suggested more pronounced weight loss and prolonged satiety in comparison with the effects achieved by vagus nerve stimulation. However, clinical studies in humans are still ongoing. Hopefully, they will reveal how we could better control body weight through this nerve.

It is obvious that our central nervous system and nerve signaling play an important role in the regulation of appetite and food intake. In addition to cutting caloric intake and increasing energy expenditure, acting on hunger signaling could potentially be an efficient strategy for obesity control as well. Nonetheless, even though the data from recent findings are promising, they require further confirmation in larger clinical trials.

References:

Amin, T., Mercer, J. G. (2016). Hunger and Satiety Mechanisms and Their Potential Exploitation in the Regulation of Food Intake. Current Obesity Reports. 5(1): 106-112. doi: 10.1007/s13679-015-0184-5

Buhmann, H., le Roux, C.W., Bueter, M. (2014). The gut-brain axis in obesity. Best Practice and Research. Clinical Gastroenterology. 28(4): 559-571. doi: 10.1016/j.bpg.2014.07.003

Prolog, J.D., Cole, S., Bergquist, S., Corn, D., Knight, J., Matta, H., Singh, A., Lin, E. (2018). Percutaneous CT Guided cryovagotomy for the management of mild-moderate obesity: a pilot trial. Emory University School of Medicine, Atlanta, GA; University at Buffalo, Buffalo, NY; Emory Healthcare, Roswell, GA; Penn State University Milton S. Hershey Medical Center, Hershey, PA. Society of Interventional Radiology’s Annual Scientific Meeting.

Browning, K.N., Verheijden, S., Boeckxstaens, G.E. (2017). The Vagus Nerve in Appetite Regulation, Mood, and Intestinal Inflammation. Gastroenterology. 152(4): 730-744. doi: 10.1053/j.gastro.2016.10.046

Image via silviarita/Pixabay.

Viatcheslav Wlassoff, PhD

Viatcheslav Wlassoff, PhD, is a scientific and medical consultant with experience in pharmaceutical and genetic research. He has an extensive publication history on various topics related to medical sciences. He worked at several leading academic institutions around the globe (Cambridge University (UK), University of New South Wales (Australia), National Institute of Genetics (Japan). Dr. Wlassoff runs consulting service specialized on preparation of scientific publications, medical and scientific writing and editing (Scientific Biomedical Consulting Services).
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