In a review recently published in Current Atherosclerosis Reports, a team of researchers from the Laboratory of Cell Signaling, Department of Internal Medicine, University of Campinas—UNICAMP in Campinas, Brazil explored the current evidence regarding the mechanisms by which Roux-en Y gastric bypass (RYGB) can alter the peripheral signals that are responsible for the modulation of the melanocortin circuits involved in the regulation of energy balance.
Roux-en-Y gastric bypass (RYGB) is a type of weight-loss surgery that reduces the size of the stomach to a small pouch, restricting the amount of food that patients can take in at meals. The surgeon then attaches the pouch directly to the small intestine, bypassing most of the rest of the stomach and the upper part of the small intestine, reducing the amount of fat and calories patients can absorb from the foods they are able to eat for even more weight loss.
Obesity is a highly prevalent disease in the world and is significantly impacting global health. Of the many systems that obesity affects, the central nervous system (CNS), which regulates the body’s energy levels, is one of them. Adiposity signals, such as insulin and leptin, gastrointestinal signals, and other stimuli feed itself reflect the body fat store, shuttling information to the brain, particularly the neuropeptidergic system in the arcuate nucleus (ARC) of the hypothalamus. The ARC has been found to modulate the energy balance through melanocortinergic second-order neurons. In the brain, food reward circuits act parallely with melanocortinergic circuitry in the management of the coordination of the energy requirements outputs that maintain a stable balance between spending and energy consumption.
The hypothalamic alterations that result from exposure to high-fat diets and low-grade inflammation contribute to the pathogenesis of obesity and to the restructuration of the energy balance. As a result, the brain changes that result from diet-induced obesity (DIO) affect brain programming to promote rescheduling in food intake, food interest, satiety signals response, and energy expenditure. These alterations contribute to a new energy balance set point in the obese brain.
In the review, the team of researchers indicated that the increase in obesity prevalence has led to substantial increase in the study of its important clinical and pathophysiological aspects, and scientific efforts have more recently tried to clarify the molecular mechanisms underlying the changes in energy balance and, particularly, the changes in hypothalamic circuitry, which are key to the evolution of pharmacotherapy.
According to the researchers, these scientific advances have contributed to a description of the installation of the hypothalamic injury as well as to how the surgery can modify the programming brain and drive it to a favorable energy balance.
However, the researchers noted that there are still many gaps in the understanding, and new avenues are opening up every day. Although RYGB has important effects on the population, including reduction in cardiovascular mortality, an in-depth understanding of how and why the surgery causes such profound changes, particularly in this hypothalamic neuronal group that regulates energy homeostasis, is lacking.
