Hunger Hormones Explained: Ghrelin, Leptin, GLP-1, PYY & Insulin

For most of the twentieth century, doctors treated hunger as a question of character. Eat less, the advice went, and if you cannot, the failing is yours. The trouble with that model is that it does not match the biology. Over the past three decades, researchers have mapped a system of hormones — chemical messengers released by the stomach, the gut, fat tissue and the pancreas — that between them decide when you feel hungry, how much you eat at a sitting, and how satisfied you feel afterwards. These signals reach the brain continuously, and they operate well below the level of conscious choice. By the time hunger registers as a feeling, the hormonal decision has already been made.

This guide walks through the five hormones that do most of the heavy lifting: ghrelin, leptin, GLP-1, peptide YY and insulin. Each is made in a different place, acts on a different timescale, and either raises or lowers your drive to eat. Understanding them individually is the first step. The more important lesson — the one that explains why diets so reliably fail and why a new class of medicines works — is what happens when you put them together and watch how the whole system behaves after weight loss. A broader overview of how these pieces fit is set out in our hunger hormones explained primer and the complete guide to appetite regulation.

Ghrelin: the hunger hormone

Ghrelin is the one hormone on this list that makes you hungry. Almost everything else the body produces to regulate appetite works in the opposite direction — telling you to stop. Ghrelin is the lone loud voice on the other side, the one that says start.

It was discovered in 1999 by Masayasu Kojima and Kenji Kangawa at the National Cardiovascular Center Research Institute outside Tokyo. They were hunting for the natural partner of an orphan receptor — a signalling dock whose matching hormone had never been found — and isolated the molecule from rat stomach extract. When they gave it to animals, the animals ate. The finding, published in Nature, identified the first known peripheral hormone whose primary job is to drive appetite up rather than down.

Where it is made and what it does

Ghrelin is produced mainly by specialised cells in the lining of the stomach, with smaller contributions from the small intestine and pancreas. It travels through the blood to the hypothalamus, the brain region that balances hunger against fullness, and switches on the neurons that drive food-seeking behaviour. The conscious result is the sensation of hunger.

Its defining feature is timing. Ghrelin climbs in the hour or two before a habitual meal, peaks just as you are about to eat, and falls sharply once food arrives in the stomach. The body learns your meal pattern and starts asking for food in advance — which is why hunger arrives so punctually at lunchtime if you always eat then. For a deeper look at this rhythm, see our article on ghrelin and dieting.

What happens after weight loss

Here is where ghrelin earns its reputation. In 2002, David Cummings and colleagues at the University of Washington measured ghrelin in people who had lost an average of 17% of their body weight on a six-month diet. Common sense says a smaller body should make less of a hunger hormone. The opposite happened: three months after the weight loss ended, ghrelin sat significantly above the pre-diet baseline. The hunger signal had been turned up, not down. In obesity, by contrast, baseline ghrelin tends to run lower than in lean people — though it still rises after diet-induced weight loss, which is the pattern that matters for anyone trying to keep weight off.

Leptin: the fullness hormone from fat

If ghrelin reports on the short term — when you last ate — leptin reports on the long term: how much energy you have banked. It is the body's fuel gauge.

Leptin was discovered in 1994 by Jeffrey Friedman and colleagues at Rockefeller University, who tracked down the gene behind a strain of mice that grew enormously obese from a single mutation. The gene turned out to encode a hormone made by fat cells. Replace the missing hormone in those mice and their overeating stopped almost overnight. Friedman named it leptin, from the Greek leptos, meaning thin.

Where it is made and what it does

Leptin is secreted by fat tissue itself, in rough proportion to how much fat you carry. More fat means more leptin. It acts on the hypothalamus to quieten the hunger-driving neurons and stimulate the fullness-driving ones, biasing the system toward satiety when energy stores are healthy. In that sense leptin lowers appetite — it is a signal that says reserves are adequate, you can ease off.

The clearest proof of its importance came from rare humans born unable to make it. In 1997, Stephen O'Rahilly, Sadaf Farooqi and colleagues at Cambridge described children with congenital leptin deficiency: severely obese from infancy, relentlessly hungry, and — remarkably — restored to near-normal appetite and weight when given leptin by injection. Without the signal, the brain behaves as though the body is starving even amid abundant fat.

What happens after weight loss and in obesity

The leptin story contains a cruel twist. When you lose weight, fat mass falls and leptin falls with it — often by more than the fat loss alone would predict. The brain reads the low leptin as a famine warning and ramps hunger up while turning energy expenditure down. So the hormone that should reward weight loss instead punishes it.

You might then expect that giving people with obesity extra leptin would curb their appetite. It barely does. The reason is that most people with obesity already have high leptin levels — their large fat mass produces plenty. What has failed is the brain's ability to hear the signal, a state called leptin resistance. The gauge reads full, but the dashboard light is broken. Our piece on leptin resistance and never feeling full covers the mechanisms — impaired transport into the brain, blunted signalling inside neurons, and hypothalamic inflammation — in more detail.

GLP-1: the satiety signal behind the medicines

GLP-1, or glucagon-like peptide-1, is the satiety hormone that has reshaped obesity medicine. It is the molecule that semaglutide and tirzepatide are built to imitate, and understanding what it does naturally explains why those drugs work.

Where it is made and what it does

GLP-1 is released by L-cells in the lower small intestine and colon when food arrives. It begins rising within ten to fifteen minutes of eating and stays elevated for an hour or more. It does several things at once: it prompts the pancreas to release insulin, but only when blood glucose is high (which makes it safe from a hypoglycaemia standpoint); it slows the rate at which the stomach empties, prolonging fullness; and it acts directly on the brain to enhance satiety and dampen the reward pull of food. Daniel Drucker at the University of Toronto, whose 2018 review remains a standard reference, helped establish this multi-tasking profile over a long research career. The net effect is to lower appetite. For more on how it produces that feeling, see how GLP-1 influences satiety and the wider science of satiety.

What happens after weight loss and in obesity

Several studies report that the meal-time rise in GLP-1 is blunted in obesity, meaning the after-eating satiety signal arrives weaker than it should. And like the other satiety hormones, GLP-1 responses can stay suppressed for a long time after dieting — part of the reason a dieted body keeps feeling under-fed. The pharmacological fix was not to coax the body into making more, but to supply a long-acting version that the brain reads as a constant, robust satiety signal.

PYY (peptide YY): the brake released after meals

Peptide YY, usually shortened to PYY, is GLP-1's close companion. The two are released from the same L-cells, at the same time, and work in the same direction — telling you that the meal is done.

Where it is made and what it does

PYY comes from the L-cells of the lower gut and is released in proportion to the calories and, especially, the protein and fat in a meal. It rises over the one to two hours after eating and acts both on the gut and on the appetite centres of the brain to reduce the desire to eat more. In 2002, Rachel Batterham and Stephen Bloom's group at Imperial College London showed in Nature that infusing the active form, PYY(3-36), into healthy volunteers cut how much they ate at a subsequent buffet by about a third. PYY is, in plain terms, a meal-termination brake.

What happens after weight loss and in obesity

Batterham's group also reported that people with obesity release less PYY after a meal than lean people do, and feel correspondingly less full — a weaker brake. After weight loss, PYY tends to fall further and stay low, alongside the other satiety hormones, contributing to the hunger that defines the post-diet state. GLP-1 and PYY are often discussed together for exactly this reason; our article on satiety hormones GLP-1, PYY and CCK treats them as a working trio.

Insulin: the metabolic hormone with an appetite role

Insulin is best known for controlling blood sugar, but it doubles as an appetite signal — and, like leptin, it is a signal the brain can stop hearing.

Where it is made and what it does

Insulin is produced by the beta cells of the pancreas and released when blood glucose rises after a meal. Its day job is to move glucose out of the blood and into cells for use or storage. But insulin also crosses into the brain, where — like leptin — it acts on the hypothalamus as an adiposity signal, reporting on the body's energy state and nudging appetite downward. In healthy people, then, insulin's central action lowers the drive to eat.

What happens in obesity and insulin resistance

The complication is insulin resistance. When cells stop responding well to insulin — a hallmark of obesity and type 2 diabetes — the pancreas compensates by pumping out more. Chronically high insulin promotes fat storage and is thought to blunt the brain's sensitivity to insulin's own appetite-lowering message, much as happens with leptin. Sharp glucose-and-insulin swings after high-glycaemic meals can also leave blood sugar dipping an hour or two later, which itself triggers renewed hunger. Our explainer on insulin resistance sets out how this develops and why it matters for weight. This is one reason hunger so often returns soon after eating — a pattern we explore under why appetite increases after dieting.

How the hunger hormones interact

No single hormone runs appetite. They form a network, and the meaning of any one signal depends on what the others are doing. The cleanest way to picture it is by timescale. Ghrelin is the short-term, pre-meal hunger pulse. GLP-1 and PYY are the after-meal brakes that build over the following hour or two. Insulin and leptin are the slower background signals reporting on stored energy — insulin minute to minute, leptin over days and weeks.

All of these converge on the same small region of the brain, the arcuate nucleus of the hypothalamus, where two opposing populations of neurons compete. One set drives hunger and conserves energy; the other drives fullness and spends it. Ghrelin pushes the first set; leptin, insulin, GLP-1 and PYY push the second. Hunger or satiety is the running tally of that contest. This is why fullness is not simply the absence of hunger — it is the active outcome of satiety signals winning out over the hunger signal in real time.

The reason this network matters so much is what it does as a whole after weight loss. Sumithran and Proietto's landmark 2011 study in the New England Journal of Medicine tracked ten appetite hormones in fifty adults for a full year after a very-low-calorie diet. A year on, the picture was bleak in a consistent direction: ghrelin was still elevated, while leptin, PYY and the other satiety signals remained suppressed. Every hormone had shifted in the direction that favours eating more — the hunger pedal pressed down, the satiety brakes eased off — and the shifts had not faded with time. The dieted body is, hormonally, a different animal from a never-dieted body of the same weight, and it is an animal built to regain.

How GLP-1 medications work on these hormones

The breakthrough behind drugs like semaglutide and tirzepatide was conceptual before it was chemical: the recognition that obesity is a problem of the hormonal environment, not of insufficient effort. Rather than ask behaviour to fight the hormones, these medicines change the hormones.

They are GLP-1 receptor agonists — molecules engineered to look enough like natural GLP-1 to switch on its receptors, but modified so the body cannot break them down within minutes the way it destroys the natural hormone. Native GLP-1 has a half-life of about two minutes; semaglutide lasts roughly a week. The result is a steady, strong satiety signal that the brain reads as well-fed even while a person is eating less. The drug slows gastric emptying so meals feel filling for longer, prompts glucose-dependent insulin release, and — importantly — acts on the brain's reward circuits to quieten the persistent pull of food that many patients call food noise. Tirzepatide goes a step further, activating the GIP receptor as well as the GLP-1 receptor.

What these medicines do not do is directly lower ghrelin. They work on the satiety side of the ledger, not the hunger side. But the practical effect addresses the same problem from the opposite direction. A diet creates a calorie deficit and leaves ghrelin to climb against it unopposed; a GLP-1 medicine creates a deficit while supplying a satiety signal strong enough that the brain does not mount the same counterattack. That is why the weight loss is defended against in one case and tolerated in the other — and it is also why the effect depends on continued treatment. Stop the medicine and the natural hormonal environment, with its elevated ghrelin and suppressed satiety signals, reasserts itself.

Key takeaways

• Ghrelin is made in the stomach and is the only major hormone that raises appetite. It peaks before meals and, after weight loss, stays elevated above baseline.
• Leptin is made by fat tissue and signals long-term energy stores, lowering appetite. In obesity the brain stops responding to it (leptin resistance), and weight loss drops it sharply, triggering hunger.
• GLP-1 is released by the gut after meals, lowers appetite through satiety, insulin release and slowed stomach emptying, and is the hormone GLP-1 medications imitate.
• PYY is released alongside GLP-1, acts as a meal-termination brake, and is blunted in obesity and suppressed after dieting.
• Insulin manages blood sugar but also lowers appetite via the brain; insulin resistance blunts that message and promotes fat storage.
• The hormones operate as a network on different timescales. After weight loss the whole system shifts toward hunger and stays there — which is why diets reliably fail and why obesity is best understood as a chronic, biologically defended condition.

The picture that emerges from this research is not one of weak will. It is one of a well-engineered system doing precisely what it evolved to do — defend the body's energy stores against loss. For a fuller treatment of how hunger and fullness are managed day to day, see the hunger and satiety guide, the hunger and satiety hub, and the broader appetite and hunger collection.