Leptin, Ghrelin, and Appetite Regulation

Appetite and body-weight regulation depend on hormonal signals that report the body's energy state to the brain. Leptin, secreted by adipose tissue in proportion to fat mass, signals long-term energy stores and tends to reduce food intake, while ghrelin, secreted mainly by the stomach, rises before meals and stimulates hunger. Together these opposing signals, integrated in the hypothalamus, illustrate how peripheral hormones govern energy balance.

Definition

Leptin is an adipose-derived hormone that signals the size of energy stores and generally suppresses appetite, whereas ghrelin is a stomach-derived peptide that rises in the fasted state and stimulates appetite; both act on hypothalamic circuits that regulate food intake and energy balance.

Scope

The entry covers leptin and ghrelin as the principal peripheral hormones of appetite control, their tissues of origin, their opposing actions on hunger and satiety, and their integration in hypothalamic circuits. It is a reference physiology topic and does not provide guidance on diagnosing or treating obesity or eating disorders.

Core questions

• How do leptin and ghrelin report opposite aspects of energy state to the brain?
• Which tissues secrete these hormones and what controls their release?
• How does the hypothalamus integrate adiposity and hunger signals to regulate food intake?

Key concepts

• Leptin as an adiposity signal
• Ghrelin as a pre-meal hunger signal
• Hypothalamic arcuate nucleus circuits
• Energy-balance homeostasis
• Satiety versus hunger signalling
• Leptin resistance

Mechanisms

Leptin is released by adipocytes in proportion to fat mass and circulates to the hypothalamus, where it acts on arcuate-nucleus neurons to reduce appetite and increase energy expenditure, functioning as a long-term adiposity signal. Ghrelin is secreted mainly by the stomach, rises before meals and falls after eating, and acts on the same hypothalamic circuits to stimulate hunger; it was originally identified as a growth-hormone-releasing peptide. The brain integrates these opposing signals along with shorter-term gut peptides to set food intake. In common obesity, elevated leptin often fails to suppress appetite effectively, a state described as leptin resistance.

Clinical relevance

Leptin and ghrelin physiology underpins understanding of hunger, satiety, and the regulation of body weight, and provides context for research into obesity and rare leptin-deficiency states. This entry describes normal physiology for educational purposes and is not a basis for individual diagnosis or weight-management treatment.

Evidence & guidelines

The discovery of leptin came from positional cloning of the mouse obese gene by Zhang and colleagues in 1994, followed by demonstration of its weight-reducing effects by Halaas and colleagues in 1995. Ghrelin was identified by Kojima and colleagues in 1999. Reviews synthesise the roles of both hormones in human appetite and weight regulation. The topic rests on this primary and review literature rather than a single clinical guideline.

History

The field was transformed in 1994 when Friedman's group cloned the obese gene and identified its product, leptin, providing molecular evidence for a circulating signal of fat mass; the weight-reducing effect of leptin was shown the following year. The complementary hunger signal, ghrelin, was discovered in 1999 as a stomach peptide that releases growth hormone and stimulates appetite, completing a picture of opposing peripheral hormones controlling energy balance.

Key figures

• Jeffrey M. Friedman
• Masayasu Kojima
• Kenji Kangawa

Seminal works

• zhang-1994
• halaas-1995
• kojima-1999

Frequently asked questions

How do leptin and ghrelin differ?

Leptin comes from fat tissue, signals plentiful energy stores, and tends to reduce appetite, whereas ghrelin comes mainly from the stomach, rises before meals, and stimulates hunger.

If leptin reduces appetite, why does it not simply cure obesity?

In common obesity leptin levels are high yet fail to suppress appetite effectively, a state described as leptin resistance, so raising leptin does not reliably reduce intake.