Why the brain stops hearing "I'm full" despite abundant fat stores.
What the evidence says
- Obesity is a state of leptin resistance with defective leptin signal transduction[1]
- Brain perceives insufficient energy despite abundant body fat — "internal starvation"[1]
- The relationship between obesity and leptin resistance is bidirectional — each can cause the other — but in diet-induced obesity, cellular leptin resistance is primarily a consequence of the obese state rather than its initial cause[2]
- Obesity promotes cellular processes that attenuate leptin signaling, preventing it from reaching the level it would otherwise attain, facilitating further weight gain[2]
- Creates a vicious cycle: obesity → resistance → more hunger → more obesity[2]
- Most obese humans have high endogenous leptin levels, not low — the problem is resistance, not deficiency[3]
- Exogenous leptin produces only modest effects (~5% weight loss) in resistant individuals, making supplementation ineffective for typical obesity[3]