Control of obesity and appetite
Obesity and appetite are one of the main challenges for human health worldwide. However, there are currently no effective pharmacological interventions for obesity. New studies have improved our understanding of energy homeostasis by classifying sophisticated neurohumoral networks that transmit signals between the brain and the gut to control food intake.
The hypothalamus is a key region that has reciprocal connections between higher cortical centers, such as the reward-related limbic pathways, and the brain stem. In addition, the hypothalamus integrates a series of peripheral signals that modulate food intake and energy expenditure. Gut hormones such as peptide YY, pancreatic polypeptide, glucagon-like peptide, oxyntomodulin, and ghrelin, are moderated by acute food ingestion.
In contrast, adiposity signals such as leptin and insulin are involved in energy homeostasis both in the short and long term. In this article, we focus on the role of gut hormones and their related neural networks (the gut-brain axis) in appetite control and their potential as new therapies for obesity.
Regulation of obesity and appetite
The global obesity and appetite epidemic is on the rise, and endocrinologists are at the forefront in diagnosing its underlying causes and prescribing treatment plans. Our latest scientific statements, Obesity Pathogenesis and the Science of Obesity Management provide a comprehensive overview of the state of the science in the field of obesity and identify areas for future research.
Central mechanisms in the regulation of obesity and appetite
In the CNS, the hypothalamus is the key region complicated in the regulation of appetite. It has before been hypothesized that satiety was controlled by the ventromedial hypothalamic nucleus and that eating was controlled by the lateral region. However, this early hypothesis has evolved into a much more complete and complex understanding of the integrated neural network responsible for appetite regulation, involving discrete pathways within specific nuclei of the hypothalamus, and various regulatory modulators.
The regulation of eating, energy intake and expenditure, and Bodyweight is a homeostatic process. General health info is connected predominantly through long-term humoral signals, whereas the initiation and termination of meals are believed to be regulated through short-term signals, such as neural signals from the brain and humoral signals from the brain. intestine.
Intestinal hormones and obesity
The GI tract is the largest endocrine organ in the body and is believed to play an important role in the regulation of appetite as a source of several regulatory peptide hormones. Postprandial satiety is believed to be regulated by a sensory system that communicates between the intestine and the appetite-regulating centers in the brain, the hypothalamus is responsible for the detection of nutrients and energy and the corresponding adjustments in food intake.
In the intestine, there is a set of endocrine cells, which synthesize and release various hormones in response to nutrient and energy intake, and these hormones have been shown to influence appetite in humans and rodents when administered at physiological levels. Distinguishing between genuine satiating effects and reductions in appetite due to nausea or feelings of poor health can potentially confuse experimental results.
Food intake is influenced not only by nutritional status but also by various palatability cues, including taste and smell. Dose administration via oral gavage can be used to mitigate potential taste aversion and/or smell and effectively allow further critical analysis of the results of such studies. Together, unlike leptin and insulin, which have been proposed to signal long-term energy status, gut hormones are believed to play a critical role in the initiation and completion of meals.
Can gut hormones control obesity and appetite?
The current obesity epidemic is driven by the availability of very tasty and high-calorie foods and the low requirement of physical activity in our modern environment. If energy consumption exceeds energy use, the extra calories are stored as body fat. Although the body has mechanisms that work to maintain body weight over time, they mainly defend against starvation and are less robust in preventing the development of obesity.
Information of this homeostatic system that controls body weight has augmented exponentially over the last decade and has revealed new possibilities for the treatment of obesity and its associated comorbidities. A therapeutic target in the development of agents based on gastrointestinal hormones that control appetite.
The serious personal, social, and economic consequences that the continued global increase in the prevalence of obesity heralds are well documented. Currently, licensed non-surgical interventions have limited efficacy. This relative failure of available therapies has prompted work aimed at harnessing the physiological mechanisms of appetite control.
The search for the body’s own satiety signals as therapeutic targets promises effective reductions in body weight with minimal disruption to other systems, avoiding the side effects that occur as an unwanted consequence of therapies targeting ubiquitous receptor and neurotransmitter complexes.