leptin and weight loss

Leptin is a human hormone that regulates appetite and energy expenditure. This hormone was only discovered in 1994. Leptin is mostly produced by the bodies fat cells, with levels being proportional to body fat. It is the binding of leptin in the brain which signals when you are full. For those who have a genetic defect so they don't produce leptin are extremely obese. However injecting leptin helps cure this.

You would expect obese people would eat less as they have a higher level of leptin, and the leptin binding in the brain is signal that you have the "full" feeling (the full feeding is know as satiety). However this is not the case. It is hypothesised that obese people have leptin Resistance, analogues to diabetics having insulin resistance.

It's not just appetite that leptin controls. When females are of very low body fat, the leptin levels drop, and thus they do not ovulate.

In 1999 a placebo double blind trial was undertaken in looking at effect of injecting leptin into obese subjects. They found that the higher the leptin dose the more weight loss that obese people lost. The graph below shows that those on the highest two levels of leptin (0.1 mg/kg and 0.3mg/kg lost significantly more than those who were on lower levels and placebo. What is fascinating is that all these subjects should have been eating the same number of calories a day. Over approximately half a year, some lost no weight, while some lost 7kg.


However what was noted that individual results varied significantly. The graph to the left looks at weight loss with respect to leptin dose. At least one person in both the 0.1 and 0.3 dose group gained between 5 - 10 kg. Now assuming that all subjects followed instructions (some might not have been honest in their reporting of food consumption) there is a massive difference in individual results. For example someone on 0.3 dose lost nearly 20kg, while others lost close to nothing. Infact compared to the placebo whose results varied between gain of 5 kg to loss of 10kg would indicate that for most people the leptin didn't enhance weight loss by much.

So we can conclude that leptin might help with weight loss - but it is no silver bullet.

References: Collier GR, de Silva A, Walder K. Leptin and the future of obesity treatment? Proceedings of the Nutrition Society of Australia 2000; 24:22-30.

Heymsfield S et al Recombinant Leptin for Weight Loss in Obese and Lean Adults: A Randomized, Controlled, Dose-Escalation Trial JAMA. 1999;282:1568-1575.