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The Hormones Behind Weight Gain: Insulin, Leptin, Ghrelin and GLP-1 Explained

Obesity involves many hormones, not just willpower. Former NIH scientist Dr. Sayantan Banerjee explains insulin, leptin, ghrelin, GLP-1, cortisol, thyroid and menopause.

OBESITY REMISSION

Dr. Sayantan Banerjee

10/31/20268 min read

People with obesity are often told that weight is simply a matter of calories in and calories out. At one level that is true. Energy balance can't be ignored. But it skips the most important question: what controls how much we want to eat, how full we feel, and how much energy we burn? The answer is a network of hormones, and when that network shifts, keeping weight stable becomes much harder.

This article walks through the main hormones involved in weight, what each does, how it can go wrong, and what you can realistically do about it. It isn't about finding one hormone to blame. It is about understanding why obesity behaves like a long-term biological condition, and why simple willpower so often isn't enough.

The control centre: your brain

Appetite and energy use are coordinated mainly in the hypothalamus, a small area at the base of the brain. It receives signals from fat tissue, the gut, the pancreas and other organs, and decides how hungry you feel and how much energy you burn.

Other parts of the brain, including the reward system, add a second layer. They make some foods more appealing than others, especially foods high in sugar, fat and salt together. That is why you can feel full after a main course and still want dessert.

Hormones are the messengers that connect the body to these brain centres.

Insulin: the storage hormone

Insulin is made by the pancreas. Its main job is to move glucose from the blood into cells, and to tell the body to store energy, as glycogen in the liver and muscles, and as fat.

In insulin resistance, the body's cells respond poorly to insulin, so the pancreas makes more of it to keep glucose under control. High insulin levels are common in people with obesity, prediabetes and early type 2 diabetes.

There is an ongoing scientific debate about how much insulin itself drives weight gain. One view, often called the carbohydrate-insulin model, argues that diets high in rapidly digested carbohydrates raise insulin, push energy into fat storage, and leave people hungrier. Another view, often associated with researchers such as Kevin Hall at the NIH, argues that total energy intake, driven by the brain, matters more, and points to controlled studies where low-carb and low-fat diets produced similar fat loss when calories were matched. The truth may differ between individuals.

What isn't in dispute is that reducing insulin resistance, through weight loss, activity and better sleep, improves metabolic health. And for many people, eating fewer refined carbohydrates helps them control hunger and glucose.

Leptin: the fullness signal from fat

Leptin is made by fat cells. The more fat you carry, the more leptin you produce. Leptin travels to the brain and tells it how much energy is stored. In theory, high leptin should reduce appetite and increase energy use.

In people with obesity, though, leptin levels are usually high, yet the brain doesn't respond as strongly as expected. This is often called leptin resistance. The signal is there, but it isn't heard clearly.

When you lose weight, leptin falls quickly, often faster than fat itself. The brain reads that fall as a sign of starvation and responds by increasing hunger and conserving energy. In the 2011 Melbourne study published in the New England Journal of Medicine, leptin was still lower than before the diet a year after weight loss. This is one of the main reasons lost weight tends to come back.

Ghrelin: the hunger hormone

Ghrelin is made mainly in the stomach. Its levels rise before meals and fall after eating. It is the main hormone that signals hunger.

After weight loss, ghrelin levels tend to rise and stay higher, which adds to the pressure to regain. Short sleep also raises ghrelin, which is one reason tired people often feel hungrier.

GLP-1, PYY and CCK: the fullness hormones from the gut

Several hormones are released by the gut after eating to tell the brain you have had enough.

GLP-1 (glucagon-like peptide-1) is released from the lower small intestine and colon. It increases insulin release after meals, reduces glucose release from the liver, slows stomach emptying, and reduces appetite. It is the hormone that medicines like semaglutide copy, at much higher and longer-lasting levels.

Peptide YY (PYY) is released from the same area and also reduces appetite.

Cholecystokinin (CCK) is released from the upper small intestine, especially in response to fat and protein, and helps you feel satisfied.

After weight loss, PYY and CCK tend to fall, making it harder to feel full. Some research suggests that people with obesity may have a smaller GLP-1 response to meals, though findings vary between studies.

The type of food you eat affects these hormones. Protein, fibre, and foods that take longer to digest tend to produce a stronger fullness response than refined carbohydrates and sugary drinks. I explain this in more detail in my article on supporting GLP-1 naturally.

Cortisol: the stress hormone

Cortisol is made by the adrenal glands and rises in response to stress, illness and lack of sleep. In the short term, it raises blood glucose to give the body energy.

Chronically high cortisol, as in the rare condition Cushing's syndrome, causes weight gain, particularly around the abdomen and face. Everyday stress doesn't usually raise cortisol to anything like those levels, but chronic stress is linked to more abdominal fat, poorer sleep, and more emotional or comfort eating. I cover this in my article on stress and belly fat.

Thyroid hormones: the metabolic thermostat

Thyroid hormones help set the body's metabolic rate. An underactive thyroid (hypothyroidism) slows metabolism and can cause modest weight gain, along with tiredness, feeling cold, dry skin and constipation.

Hypothyroidism is common, especially in women, and is easily checked with a blood test for TSH (thyroid-stimulating hormone). If it is found, treatment with levothyroxine restores normal levels. But it is worth being realistic. The weight gain from hypothyroidism is usually a few kilograms, mostly from fluid, and treating it rarely leads to large weight loss on its own.

Sex hormones: menopause, PCOS and testosterone

Menopause. As oestrogen falls around menopause, fat storage tends to shift from the hips and thighs to the abdomen. Many women notice their waist growing even if their weight changes little. Sleep disruption from hot flushes can add to appetite changes. Strength training, protein and good sleep become especially important at this stage.

Polycystic ovary syndrome (PCOS). PCOS affects many women of reproductive age. It is closely linked to insulin resistance and is associated with weight gain, difficulty losing weight, and a higher risk of type 2 diabetes. Weight loss, even of 5% to 10%, often improves symptoms.

Testosterone in men. Low testosterone is more common in men with obesity, and obesity itself can lower testosterone. Weight loss often raises it. Testosterone treatment is sometimes used, but only for men with confirmed low levels and symptoms, under specialist guidance.

Medicines that affect weight

Some commonly used medicines can cause weight gain, including some antidepressants, antipsychotics, anti-epilepsy drugs, steroids, beta-blockers, and some diabetes treatments such as insulin and sulfonylureas. If you think a medicine is affecting your weight, talk to your doctor. There are often alternatives. Never stop a prescribed medicine on your own.

Why this matters: obesity is a biological condition

Put together, these hormones show why obesity is now widely described as a chronic disease rather than a lifestyle choice. The body has many overlapping systems that defend body weight, and after weight loss several of them push in the same direction: more hunger, less fullness, and lower energy use.

That doesn't mean nothing can be done. It means effective approaches work with this biology, rather than relying on willpower alone.

What you can do

You can't switch these hormones off, but you can influence many of them.

Eat protein and fibre at every meal. These increase fullness hormones and slow digestion.

Choose whole foods over ultra-processed ones. In a controlled NIH study, people ate about 500 calories a day more on an ultra-processed diet, even with the same nutrients available.

Sleep seven or more hours. Short sleep raises ghrelin and lowers leptin in laboratory studies, and extending sleep reduced calorie intake in a 2022 US trial.

Be active every day, and build muscle. Activity improves insulin sensitivity, and muscle helps limit the slowdown in metabolism after weight loss.

Manage stress. Exercise, time outdoors, social contact and structured relaxation can all help.

Get checked for treatable causes. If you have symptoms, ask about thyroid tests, PCOS, low testosterone, or medicines that may be affecting your weight.

Consider medication where appropriate. GLP-1 medicines work directly on appetite hormones. For people with obesity, they can be a reasonable part of treatment, discussed with a doctor.

Hormone myths you'll see online

Because hormones really do matter for weight, they attract a lot of misleading claims. A few to watch out for:

"Adrenal fatigue is making you gain weight." Adrenal fatigue isn't a recognised medical diagnosis. The Endocrine Society and other expert bodies have said there is no good evidence for it. True adrenal problems exist, such as Addison's disease and Cushing's syndrome, and need proper testing. Treating supposed adrenal fatigue with supplements or steroids can be harmful.

"A hormone-balancing diet will reset your metabolism." There is no single diet that balances all hormones. The changes that genuinely help, such as eating more protein and fibre, fewer ultra-processed foods, sleeping well and staying active, are the same ones discussed throughout this article.

"Thyroid supplements will boost your metabolism." Over-the-counter thyroid support products may contain variable amounts of iodine or even thyroid hormone. They can cause real thyroid problems. If you think your thyroid may be underactive, ask for a blood test rather than self-treating.

"Insulin is the only thing that matters." Insulin is important, but appetite, energy use and weight are controlled by many hormones and by the brain. Focusing on one hormone alone oversimplifies a complex system.

"Saliva hormone tests explain your weight." Many direct-to-consumer hormone tests aren't validated for diagnosing weight-related problems, and results can be misleading.

If you see a product or plan claiming to fix your hormones for weight loss, ask what evidence supports it, and check with your doctor or pharmacist before spending money or taking anything new.

How my book can help

The Obesity Exit Strategy is built on the idea that obesity is a multi-hormone condition. It explains how insulin, appetite signalling and GLP-1 interact, and how food structure, intermittent fasting, exercise, sleep and stress influence them. You do not need another extreme diet. You need to understand why your hunger, metabolism and weight regulation have changed. See the book page.

Frequently asked questions

Which hormone causes belly fat? Several are involved, including insulin, cortisol and falling oestrogen during menopause. Excess calories, alcohol, poor sleep and inactivity also play a big part.

What is leptin resistance? When leptin levels are high but the brain responds less than expected, so appetite isn't reduced as it should be.

Can a hormone test explain my weight gain? Sometimes. Thyroid problems, PCOS and low testosterone can be checked. But most obesity involves many small changes rather than one abnormal hormone.

Does insulin make you fat? Insulin promotes energy storage, and high insulin levels are common in obesity. Scientists still debate how much insulin itself drives weight gain compared with total energy intake.

How can I lower ghrelin? Eating enough protein, sleeping well and avoiding very long gaps between meals can help keep hunger more stable.

Are hormones the reason I can't lose weight? They make it harder, especially after weight loss, but changes to food, activity, sleep and sometimes medication can still work.

Can birth control or HRT cause weight gain? Studies of most hormonal contraceptives and HRT haven't found large average weight changes, although individuals vary. If you are concerned, talk to your doctor about options.

Why is it harder to lose weight after 40? Muscle mass tends to fall with age, activity often drops, sleep can worsen, and in women menopause shifts fat to the waist. These changes make it harder, not impossible.

Should I ask for a full hormone panel? Usually a targeted approach works better. Your doctor will choose tests based on your symptoms, such as thyroid function, HbA1c, and specific tests if PCOS, low testosterone or Cushing's is suspected.