[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Nutritional pathology](https://durgical.com/en/general-pathology/#a-nutrition) › Obesity: leptin, adipokines and its consequences

[General pathology](https://durgical.com/en/general-pathology/) · [Nutritional pathology](https://durgical.com/en/general-pathology/#a-nutrition)

# Obesity: leptin, adipokines and its consequences

- Mechanism

Fat tissue is an endocrine organ; in obesity it sends wrong signals to the brain and inflames the body, causing diabetes, liver and heart disease.

Updated 2026-11-01

## Key points

- Leptin: from fat, reduces appetite via POMC/MC4R; common obesity = leptin resistance.
- MC4R mutations are the most common monogenic cause of obesity; congenital leptin deficiency is rare.
- Adiponectin is low in obesity; visceral fat is the most harmful.
- Endometrial cancer and obesity: aromatase in fat makes oestrogen.
- Prader-Willi syndrome: hyperphagia and obesity with high ghrelin.

## What it is

Body weight is controlled by signals from fat (leptin), the gut (ghrelin, GLP-1, PYY) and the hypothalamus. In common obesity the brain becomes resistant to leptin, and enlarged visceral fat releases free fatty acids and cytokines that cause insulin resistance and chronic low-grade inflammation. Obesity is rising fast in Latin America, where it often coexists with undernutrition.

## Step by step

- Leptin from fat acts on the arcuate nucleus: it activates POMC/CART neurons and inhibits NPY/AgRP neurons.
- α-MSH from POMC neurons acts on MC4R: less appetite and more energy expenditure.
- In common obesity leptin is high but the brain responds poorly (leptin resistance).
- Large visceral adipocytes become hypoxic, die and attract macrophages that form crown-like structures.
- Macrophages release TNF and IL-6, adiponectin falls and free fatty acids flood the liver.
- Insulin resistance in muscle and liver: hyperinsulinaemia, type 2 diabetes, dyslipidaemia and MASLD.
- Extra fat also makes oestrogen (aromatase), raises intra-abdominal pressure and loads joints.

## Signals that control body weight

| Signal | Source | Effect on appetite | In obesity |
| --- | --- | --- | --- |
| Leptin | Adipocytes | Decreases | High, but the brain is resistant |
| Adiponectin | Adipocytes | Improves insulin sensitivity | Low |
| Ghrelin | Stomach | Increases (before meals) | Raised after weight loss |
| GLP-1 and PYY | Intestine | Decrease; slow gastric emptying | Response may be blunted |
| Insulin | Pancreas | Decreases (in the brain) | High with insulin resistance |

## Clinical notes

- Consequences: type 2 diabetes, hypertension, dyslipidaemia, atherosclerosis, MASLD, obstructive sleep apnoea, gallstones, osteoarthritis, GERD, PCOS.
- Obesity raises the risk of endometrial, breast (after menopause), colorectal, kidney, liver and oesophageal adenocarcinoma.

## Memory aid

Leptin shouts ‘enough’, but the obese hypothalamus has stopped listening.

## Test yourself

Think of the answer, then tap the question to see it.

## Why do most people with obesity have high leptin levels?

Leptin is made in proportion to fat mass; in common obesity the hypothalamus becomes resistant to it.

## Which hormone from fat improves insulin sensitivity and is low in obesity?

Adiponectin.

## How does obesity raise the risk of endometrial cancer?

Aromatase in adipose tissue converts androgens to oestrogen, which stimulates the endometrium without progesterone opposition.

## Which gene mutation is the most common single-gene cause of obesity?

Mutations of the melanocortin-4 receptor (MC4R).

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/general-pathology/obesity-leptin-adipokines-and-its-consequences/)

## Related

- [Fatty change (steatosis)](https://durgical.com/en/general-pathology/fatty-change/)
- [Chronic inflammation: causes, cells and features](https://durgical.com/en/general-pathology/chronic-inflammation-causes-cells-and-features/)
- [Diet, cancer and systemic disease](https://durgical.com/en/general-pathology/diet-cancer-and-systemic-disease/)
- [Hypertrophy: physiologic and pathologic](https://durgical.com/en/general-pathology/hypertrophy-physiologic-and-pathologic/)

## Related conditions

- [Obesity](https://durgical.com/en/conditions/obesity/)
- [Type 2 diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/)
- [Metabolic dysfunction-associated steatotic liver disease (MASLD/NAFLD)](https://durgical.com/en/conditions/metabolic-dysfunction-associated-steatotic-liver-disease/)
- [Metabolic syndrome](https://durgical.com/en/conditions/metabolic-syndrome/)
- [Arterial hypertension](https://durgical.com/en/conditions/arterial-hypertension/)
- [Atherosclerosis and dyslipidaemia](https://durgical.com/en/conditions/atherosclerosis-and-dyslipidaemia/)
- [Obstructive sleep apnoea](https://durgical.com/en/conditions/obstructive-sleep-apnoea/)
- [Obesity hypoventilation syndrome](https://durgical.com/en/conditions/obesity-hypoventilation-syndrome/)
- [Gallstones (cholelithiasis)](https://durgical.com/en/conditions/gallstones/)
- [Knee Osteoarthritis](https://durgical.com/en/conditions/knee-osteoarthritis/)
- [Polycystic ovary syndrome](https://durgical.com/en/conditions/polycystic-ovary-syndrome/)
- [Endometrial cancer](https://durgical.com/en/conditions/endometrial-cancer/)
- [Gastro-oesophageal reflux disease (GERD)](https://durgical.com/en/conditions/gastro-oesophageal-reflux-disease/)
- [Prader–Willi and Angelman syndromes (imprinting)](https://durgical.com/en/conditions/prader-willi-and-angelman-syndromes/)

## Elsewhere in DurgiPedia

- [Leptin, appetite and obesity](https://durgical.com/en/biochemistry/topics/leptin-appetite-and-obesity/)
- [Energy balance, food intake and obesity](https://durgical.com/en/physiology/energy-balance-food-intake-and-obesity/)
- [Appetite hormones: leptin, ghrelin and incretins](https://durgical.com/en/physiology/appetite-hormones-leptin-ghrelin-and-incretins/)
- [Adipose tissue: white and brown fat](https://durgical.com/en/histology/adipose-tissue-white-and-brown-fat/)
- [Insulin signalling](https://durgical.com/en/biochemistry/topics/insulin-signalling/)
- [Aromatase (CYP19A1)](https://durgical.com/en/biochemistry/enzymes/aromatase/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Obesity and overweight](https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight) (World Health Organization, 2026); [Epidemiologic and Etiologic Considerations of Obesity](https://www.ncbi.nlm.nih.gov/books/NBK585067/) (StatPearls (NCBI Bookshelf), 2025).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/general-pathology/obesity-leptin-adipokines-and-its-consequences/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/obesity-leptin-adipokines-and-its-consequences/