Leptin, Ghrelin and GLP-1: The Hormones Behind Hunger

Hunger can feel like a character test. Biology says otherwise: your body runs a constant conversation between your gut, fat tissue and brain about whether to eat. Three hormones come up most often in that conversation: ghrelin, leptin and GLP-1.

Ghrelin: the “start eating” signal

Ghrelin is made mostly in the stomach. It rises before meals and falls after you eat. Researchers describe it as a fast-acting signal involved in starting a meal. Injected into people, it increases appetite and food intake.

Leptin: the long-term fuel gauge

Leptin is released by fat tissue and tells the brain how much energy is stored. It works more slowly than ghrelin and is involved in the long-term regulation of body weight. Higher body fat generally means higher leptin levels. Rare genetic leptin deficiency causes severe obesity, and treating it with leptin helps. In most people with obesity, though, leptin is already high, and extra leptin does not reduce appetite much.

GLP-1: the “that is enough” signal

GLP-1 (glucagon-like peptide-1) is released by the intestine after you eat. It slows stomach emptying, helps the pancreas release insulin when blood sugar rises, and acts on the brain to reduce hunger. Naturally it breaks down within minutes. Medications in the GLP-1 class are designed to act longer, which is why they affect appetite so strongly. For what the trials found, see our research explainer.

How they fit together

Reviews describe these signals as interdependent. Several hormones need others, including leptin, to work properly. The picture is much more complicated than three names, and many other signals, such as PYY, insulin and cholecystokinin, are involved as well.

Why this matters when you lose weight

In a well-known 2011 study in the New England Journal of Medicine, Sumithran and colleagues followed adults who lost weight on a very low-calorie diet. After the weight loss, leptin was lower, ghrelin was higher and participants reported more hunger. A year later, many of those changes had not returned to baseline. The study was small and does not show these changes cause regain, but it supports something many people feel: after weight loss, hunger can be louder.

It also explains why plateaus and regain are not signs of weak character. We cover the related energy-use side in why plateaus happen.

What you can and cannot change

• Sleep: short sleep has been linked to higher ghrelin and lower leptin in small studies. See our sleep and weight guide.
• Protein and fiber: both tend to increase fullness after meals.
• Regular meals: ghrelin follows habitual meal times, so a steady pattern can make hunger more predictable.
• Supplements that claim to “balance hormones”: there is no reliable evidence that over-the-counter products fix leptin or ghrelin.

The short version

Appetite is regulated by hormones you do not consciously control. Understanding that can take some of the guilt out of hunger and make planning easier. Questions about hormones, metabolism or medication belong with a licensed clinician.

Sources

• Klok MD, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obesity Reviews, 2007 (PubMed 17212793).
• Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. New England Journal of Medicine, 2011.
• Reviews of GLP-1 as a gut-brain hormone regulating food intake and glucose: CNS Drugs, 2014 (doi 10.1007/s40263-014-0178-y).
• National Institute of Diabetes and Digestive and Kidney Diseases (niddk.nih.gov), overview pages on weight regulation.