General pathology · Nutritional pathology
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
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.
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).
Related
- Fatty change (steatosis)
- Chronic inflammation: causes, cells and features
- Diet, cancer and systemic disease
- Hypertrophy: physiologic and pathologic
Related conditions
- Obesity
- Type 2 diabetes mellitus
- Metabolic dysfunction-associated steatotic liver disease (MASLD/NAFLD)
- Metabolic syndrome
- Arterial hypertension
- Atherosclerosis and dyslipidaemia
- Obstructive sleep apnoea
- Obesity hypoventilation syndrome
- Gallstones (cholelithiasis)
- Knee Osteoarthritis
- Polycystic ovary syndrome
- Endometrial cancer
- Gastro-oesophageal reflux disease (GERD)
- Prader–Willi and Angelman syndromes (imprinting)
Elsewhere in DurgiPedia
- Leptin, appetite and obesity
- Energy balance, food intake and obesity
- Appetite hormones: leptin, ghrelin and incretins
- Adipose tissue: white and brown fat
- Insulin signalling
- Aromatase (CYP19A1)
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 (World Health Organization, 2026); Epidemiologic and Etiologic Considerations of Obesity (StatPearls (NCBI Bookshelf), 2025).
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Representative model, for educational purposes only.