Leptin, Ghrelin And How Appetite Is Signalled

Hunger is often treated as a matter of willpower. It is generated by a signalling system with defined inputs, and the system's design is asymmetric in an important way.

Two different questions, two different signals

Ghrelin is produced mainly by the stomach, rises before expected meals and falls after eating. It reports the short-term question of whether food has arrived recently.

Leptin is produced by fat tissue in proportion to its mass and changes slowly. It reports the long-term question of how much stored energy exists.

Both act on the hypothalamus, where their signals are integrated with information from the gut, the taste system and the brain's reward pathways.

The system defends downwards more than upwards

Falling leptin, which follows a reduction in fat mass, produces powerful responses: increased hunger, heightened attention to food and a reduction in energy expenditure.

Rising leptin produces a much weaker response in the other direction. The brakes on eating are considerably less forceful than the accelerator on eating during shortage.

This asymmetry makes sense for an animal whose historical risk was scarcity, and it is why the regulation of body weight is not symmetrical in either direction.

Leptin resistance explains an apparent paradox

People with more fat tissue have higher leptin, which by the simple model should suppress appetite strongly. In practice the signal is registered less effectively.

The receiving pathways become less responsive, so the brain behaves as though stores were lower than they are. High leptin and a hunger signal coexist.

This is why leptin itself is not a treatment except in the rare cases where it is genuinely absent, and those cases are diagnosed and managed by specialists.

The gut sends many more signals than these two

A range of hormones released from the intestine during and after a meal contribute to satiety, slowing stomach emptying and signalling to the brain that nutrients have arrived.

These respond to what was eaten as well as how much, which is one mechanism behind the observation that different foods of similar energy content produce different fullness.

Several modern medications act on these pathways, which is a pharmacological subject rather than a lifestyle one and firmly a matter for prescribing clinicians.

Sleep and stress feed into the same system

Short sleep is associated with changes in these appetite signals and with increased reported hunger, which is one route by which sleep affects eating.

Cortisol and the reward system also modify food intake independently of energy need, which is why eating patterns change under stress in ways hunger signalling alone does not explain.

Anyone with a marked unexplained change in appetite, in either direction, should have it assessed, since it accompanies a wide range of medical and psychological conditions.