I asked the question “By what mechanisms is appetite regulated by leptin in humans? Please explain with references (original research articles)” on https://insightai.dev/project. Here is the answer:
Summary 1
Leptin is a hormone primarily produced by adipose tissue that plays a crucial role in regulating appetite and energy balance in humans. It communicates the body’s energy status to the central nervous system, particularly the hypothalamus, influencing feeding behavior and energy expenditure. The mechanisms by which leptin regulates appetite involve complex interactions between various neuroendocrine pathways and peripheral signals.
Leptin acts on specific receptors in the hypothalamus, particularly the long form of the leptin receptor (LepRb), which is expressed in key brain regions involved in appetite regulation, such as the arcuate nucleus (ARC) and the paraventricular nucleus (PVN). Upon binding to LepRb, leptin activates several intracellular signaling cascades, including the JAK2/STAT3 pathway, which is critical for mediating its anorexigenic effects. This signaling leads to the suppression of orexigenic neuropeptides like neuropeptide Y (NPY) and agouti-related peptide (AgRP), while promoting the expression of anorexigenic peptides such as pro-opiomelanocortin (POMC) (Journal of chemical neuroanatomy).
In addition to its central effects, leptin also influences peripheral signals that regulate appetite. For instance, it enhances the action of gastrointestinal hormones like cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1), which are released in response to food intake and contribute to satiety. CCK, in particular, acts on vagal afferent neurons to inhibit food intake, and its effects are potentiated by leptin (Current opinion in endocrinology, diabetes, and obesity). Furthermore, leptin modulates the release of other hormones involved in appetite regulation, such as insulin and ghrelin, creating a feedback loop that helps maintain energy homeostasis (Molecular and cellular endocrinology).
Leptin’s role in appetite regulation is also influenced by energy balance and metabolic state. In conditions of negative energy balance, such as fasting, leptin levels decrease, which can lead to increased appetite through the stimulation of orexigenic pathways. Conversely, elevated leptin levels in states of positive energy balance signal satiety and reduce food intake (Advances in experimental medicine and biology). However, in obesity, a phenomenon known as leptin resistance occurs, where the brain becomes less responsive to leptin despite high circulating levels. This resistance is associated with various metabolic disorders and complicates weight management strategies (Advances in experimental medicine and biology).
Moreover, exercise has been shown to interact with leptin signaling, enhancing its effects on appetite regulation and energy expenditure. Physical activity can influence the secretion of leptin and other appetite-regulating hormones, contributing to a more favorable energy balance (Obesity reviews). The interplay between leptin, exercise, and other hormonal signals underscores the complexity of appetite regulation and the need for a multifaceted approach to understanding and treating obesity.
In summary, leptin regulates appetite through a network of central and peripheral mechanisms, involving direct actions on hypothalamic neurons, modulation of gastrointestinal hormones, and interactions with other metabolic signals. Understanding these pathways is essential for developing effective interventions for obesity and related metabolic disorders.
Citations 1
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