Leptin and ghrelin: The weight control hormones

Weight maintenance is one of the most challenging tasks of our everyday lives. Some prefer intermittent dieting, and some try staying on a long-term diet to fetch the results they expect. Then, there is a keto diet that focuses on consuming high-calorie foods instead of carbs. By the end of the day, many forget that fat storage and fat oxidizing hormones are our system’s weight control drivers. These hormones are leptin and ghrelin — “the satiety and hunger hormones.” Some diet regimes increase leptin, and some others increase ghrelin. You must understand these hormones’ activity to plan your diet because “no one diet fits all.”

What are leptin and ghrelin hormones?


Ghrelin is a peptide hormone secreted from the lining of the stomach and small intestine. It gained the spotlight because of its growth hormone-like activity. When your stomach is empty, it acts on the Hypothalamus, increasing appetite. Ghrelin is high before a meal, signaling you to eat, and decreases soon after.

It makes you eat more food, calories, and stores fat. Hence, reducing ghrelin production is a possible way of reducing weight. The fuller you feel, the less you eat. This relation should mean that people who eat constantly should have high levels because they are never full. Research suggests that the level is lower in obese than in an average individual because they have faulty ghrelin and ghrelin receptors, leading to increased calorie intake. 

Hence, regardless of how much fat you have, more ghrelin will always make you feel hungrier, and you eat more.

Why is ghrelin a fat-storage hormone?

Ghrelin is an orexigenic agent that increases appetite and decreases energy expenditure. However, ghrelin’s activity is not only mainstream but also progresses through other pathways. 

For instance, fat in brown adipose tissues undergoes oxidation, and in white adipose tissue undergoes storage. Ghrelin increases fat storage in white adipose and decreases thermogenesis in brown adipose tissues. As a result, ghrelin ultimately shifts food preference towards high-fat diets and increases weight.


Leptin is a hormone produced by fat cells, which communicate to the brain about the total body fat. It is an anorexigenic agent, which suppresses appetite and makes you feel fuller — “satiety hormone .” When you eat, leptin rises along with body fat — you eat less and burn more. It also expresses its effects on reproduction, blood pressure, and immune response.

High leptin levels translate to weight loss and vice-versa. Since fat cells produce leptin, the level is directly proportional to the body fat. The levels are lower when you are thin and higher when you are fat.

Besides, leptin is also a part of the reward system. When leptin levels are low, food is rewarding. When the level is high, you don’t need so much food to feel good.

Leptin, ghrelin, and sleep

Lack of sleep increases the chances of eating most of the calories at night. This routine can increase weight. Lack of sleep also influences one to eat high-calorie food and junk. More sleep can reduce sugar craving leading to controlled weight. Good rest also promotes proper insulin function. This essentially means that sleep deprivation interferes with the ghrelin leptin balance, affecting you by increasing your weight.

How leptin and ghrelin act in decreasing and increasing food intake?

The two cell groups which play a role in appetite control are NPY/AgRP and POMC/CART. The former increases appetite, and the latter suppresses appetite. These two groups interact with each other to regulate body weight. 

Ghrelin acts on NPY/AgRP neurons to release orexigenic agents, increasing food intake and reducing energy expenditure. Also, they act as antagonists of melanocortin pathways that otherwise decrease food intake. Subsequently, GABA release is enormous, which further inhibits the melanocortin pathway.

On the other hand, leptin acts on the POMC/CART pathways, decreasing food intake and increasing energy expenditure, further engaging the melanocortin pathways. This pathway also plays a role in glucose homeostasis. Leptin microinjections can treat hyperinsulinemia and normalize blood glucose levels. Moreover, it inhibits the NPY neurons of orexigenic pathways to suppress appetite.

What happens when Ghrelin levels are high?

A study suggested that Prader-Willi syndrome is a characteristic disorder of high ghrelin levels — constant hunger with maladaptive behaviors like binge eating and hoarding. We know that drug abuse is very addictive because it releases Dopamine in the VTA. 

Maladaptive food-seeking also indicates the activation of dopaminergic pathway similar to drug addiction. Ghrelin is highly expressed in tyrosine hydroxylase neurons within the VTA. A minute induction of these neurons can increase food intake, whereas injection of antagonists can reduce food intake. Ghrelin can also induce dopamine-flow in the system correlating to its maladaptive food-seeking behaviors. 

How do leptin and ghrelin levels change during a diet?

Ghrelin levels during a diet

Soon after you stop eating, ghrelin levels rise. This rise is constant for a couple of weeks. Hence, with a long diet, you lose more fat, increase ghrelin levels, and feel hungrier. It is challenging to maintain this new weight. Moreover, a diet increases cortisol levels (stress hormone) that may make your brain less receptive to leptin, causing you to overeat.

Eating disorders like anorexia and bulimia were once considered psychiatric disorders. But further studies into the complication indicated high levels of fasting plasma ghrelin.

Leptin and dieting

During a diet, leptin levels drop drastically. When leptin drops, your brain thinks you are starving and starts using up the fat stores and reduces your zeal to exercise and burn calories. Because it is one of the diets with minimal exercise, people started considering leptin diets for weight loss. However, you should avoid putting yourself into a low-calorie diet because your leptin levels can drop down, reducing your metabolic rate. This slow rate makes it more difficult to lose body fat.

But, the diet requires strict portion control and is tougher than a typical diet. It is always best to talk to a counselor about a personalized diet because “no one diet fits all”. The best way is to combine it with regular exercise for healthy weight loss.

Does more leptin mean more weight loss?

Although we know that leptin signals your brain to stop eating because you have enough energy resources, it doesn’t necessarily mean more leptin equals more weight loss. This translates to obese having less leptin, but that is not true. Their bodies are always high on leptin, but due to “leptin resistance, ” the signal will not reach their brains. Their brain thinks that the body is still starving — they eat more and exercise less to conserve energy.

Reasons for this resistance include inflammation in Hypothalamus, high free fatty acids (interfere with leptin signaling), and high initial leptin level. A mutation in the MC4R gene is also a cause. Reducing insulin resistance and triglycerides in the diet seem like a possible treatment for leptin-resistance obesity.

The bottom line is that your laziness and sedentary lifestyle may not be the only reason for your obesity. It may also be a consequence of hormonal changes. 

Can you use leptin supplements for weight loss?

Leptin supplements are also available in the market. People prefer using them to increase leptin for subsequent weight loss. But, most supplements don’t contain the hormone. Since it is a digestible protein that doesn’t enter the bloodstream, you cannot take it in the form of a pill. The pills are instead a mix of nutrients that reduce inflammation and increase leptin sensitivity. Thus, compared to other weight loss supplements, leptin pills’ weight loss activity remains unclear.

Instead of relying on these pills, it is best to eat enough fiber and protein, making you feel fuller, sending a satiety signal to your brain. Limit fructose, simple carbs, and triglycerides, all of which disrupt both insulin and leptin balance. Include supplements that promote a healthy inflammatory response like omega-3 fatty acids. Avoid cutting down on calories, exercise regularly, and get enough sleep to promote healthy leptin.

Related: How does your body respond to a fast?

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