Leptin Resistance
Leptin resistance — the brain stops responding to the 'fullness' hormone leptin, so hunger stays high and metabolism slows even when fat stores are plentiful.
Plain English
Patient-Friendly Explanation
Leptin is the hormone that tells your brain you have enough energy stored, so you feel full and burn calories at a normal rate. In leptin resistance, the brain stops responding properly to this signal and keeps acting as if the body is starving. The result is persistent hunger, a slower metabolism and a strong drive to eat, even when fat stores are plentiful.
Medical
Clinical Definition
Leptin resistance refers to the impaired central response to the adipocyte-derived hormone leptin, typically in the setting of obesity and chronic overnutrition. Despite elevated circulating leptin (hyperleptinaemia), signalling through the leptin receptor and downstream melanocortin pathways in hypothalamic POMC and AgRP neurons is blunted, with mechanisms including leptin-receptor downregulation, suppressor-of-cytokine-signalling-3 (SOCS3) induction, endoplasmic reticulum stress, hypothalamic inflammation and impaired blood-brain barrier transport. The resulting loss of anorexigenic tone promotes hyperphagia, reduced energy expenditure and ectopic fat accumulation, and is a key driver of weight regain after dieting. Leptin replacement is effective only in the rare congenital leptin deficiency and lipodystrophy states, not in common obesity.
Key Insight
Why It Matters
This is why 'just eating less' is so hard for some patients — the problem is the brain's response to leptin, not a lack of willpower. Recognising leptin resistance helps Dr Joseph Wang explain why hunger can feel overwhelming and why medically supported treatment is often needed.
Sources
Reviewed against standard medical references.
Medically reviewed by
Family Physician & Registered Acupuncturist, Accord Medical Clinic. MBBS (NUS), Graduate Diploma in Family Medicine (NUS), Graduate Diploma in Acupuncture (Singapore College of TCM).
Last reviewed: September 2026
This page is general health education, not medical advice. Whether any treatment is appropriate for you is a decision made in consultation after assessment.
