Appetite Regulation, Leptin, and Ghrelin

Appetite regulation is the hormonal and neural control of hunger and satiety that matches food intake to the body's energy needs. Two hormones illustrate the opposing signals: leptin, secreted by fat in proportion to energy stores, signals sufficiency over the long term, while ghrelin, secreted by the stomach, rises before meals and stimulates hunger.

Definition

Appetite regulation is the system by which peripheral hormonal and neural signals, integrated chiefly in the hypothalamus and brainstem, control the initiation and termination of eating; leptin is an adipocyte-derived hormone signalling energy sufficiency, and ghrelin is a stomach-derived peptide that stimulates appetite.

Scope

The topic covers the gut-brain and adipose-brain signalling that governs feeding, focusing on leptin and ghrelin as prototypical long-term and short-term signals, the hypothalamic circuits that integrate them, and the concept of leptin resistance in obesity. It is framed as physiology underlying energy balance, not as clinical guidance.

Core questions

• How do the brain and periphery communicate to start and stop eating?
• What distinguishes long-term adiposity signals such as leptin from short-term meal signals such as ghrelin?
• Why does high circulating leptin in obesity fail to suppress appetite?

Key concepts

• Leptin as an adiposity signal
• Ghrelin as a pre-meal hunger signal
• Hypothalamic melanocortin circuit (POMC and AgRP neurons)
• Short-term satiety signals (for example cholecystokinin, PYY, GLP-1)
• Leptin resistance
• Set-point defence of body weight

Mechanisms

Energy stores and meal status are communicated to the brain by hormones acting on the arcuate nucleus of the hypothalamus. Leptin, released by adipose tissue in proportion to fat mass, activates anorexigenic POMC neurons and inhibits orexigenic AgRP neurons, reducing food intake and permitting energy expenditure. Ghrelin, secreted by the stomach and rising before meals, has the opposite effect, stimulating AgRP neurons and promoting hunger. Short-term satiety peptides from the gut terminate individual meals. In common obesity, leptin levels are high yet fail to restrain intake, a state described as leptin resistance, so the system continues to defend an elevated body weight.

Clinical relevance

The discovery of leptin and ghrelin reframed appetite as a hormonally regulated process and explained why body weight is biologically defended. This entry summarises that physiology for educational reference; it is not a basis for diagnosing or treating appetite or weight disorders in individuals.

Evidence & guidelines

The topic rests on landmark molecular discoveries (the cloning of leptin and the identification of ghrelin) and on integrative reviews of central appetite control. These are primary studies and narrative reviews; the entry describes the mechanisms rather than prescribing interventions.

History

The 1994 positional cloning of the obese (ob) gene revealed leptin and established adipose tissue as an endocrine organ signalling energy stores to the brain. The 1999 identification of ghrelin added a peripheral hunger signal, and subsequent work mapped the hypothalamic melanocortin circuits that integrate these and other signals, consolidating a model of appetite as a regulated, feedback-controlled system.

Debates

What causes leptin resistance in obesity?

Despite high leptin levels, obese individuals do not suppress appetite as expected; whether this reflects impaired transport, receptor signalling defects, or other mechanisms remains debated and bears on therapeutic strategy.

Key figures

• Jeffrey Friedman
• Masayasu Kojima
• Kenji Kangawa
• Michael Schwartz

Seminal works

• zhang-1994
• kojima-1999
• morton-2006

Frequently asked questions

What do leptin and ghrelin do?

Leptin is released by fat in proportion to energy stores and signals sufficiency, tending to reduce appetite, while ghrelin is released by the stomach before meals and stimulates hunger.

If leptin reduces appetite, why are obese people not protected by their high leptin?

In common obesity leptin is elevated but no longer effectively suppresses appetite, a state called leptin resistance, so the body continues to defend a higher weight.