ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Endocrinology. 2018 Jul 1;159(7):2676–2682.

The authors compared the effects of leptin versus weight loading using intraperitoneal weighted capsules (‘gravitostat stimulation’) on changes in fat mass in mice. Leptin infusion suppressed body weight and fat mass in lean but not in overweight or obese mice. Weight loading decreased body weight in overweight and obese mice.

We thought that leptin was the major regulator of fat mass. These authors found evidence for another potent regulator, named the ‘gravitostat’. They found that increased loading using weighted capsules decreased body weight and fat mass. We are familiar with a similar concept from studies showing the role of bone sensors to weight on skeletal strength. Now we learn that the gravitostat regulates fat mass independently of fat-derived leptin secretion and circulating levels.

Leptin infusion suppressed body weight and fat mass in lean mice given normal chow but not in overweight or obese mice given a high-fat diet. The same disappointment was evident years ago when leptin failed to reduce human obesity. The intraperitoneal implantation of weight capsules had only a nonsignificant tendency to reduce body weight in lean mice, but was more effective in obese mice. The gravitostat regulates fat mass via a circuit based on weight sensors in the osteocyte that amplified the expression of the obesity-promoting neuropeptides AgRP and NPY in the arcuate nucleus. These findings demonstrate that the gravitostat regulates fat mass in obese mice, whereas leptin regulates fat mass only in lean mice with low endogenous serum leptin levels.

Thus, leptin and the gravitostat are preferentially active in mice with relatively low and high body weight, respectively. Leptin suppressed body weight and fat mass in lean mice Increased loading using intraperitoneal capsules with different weights decreased body weight in overweight and obese mice.

It sounds so simple: add external weight and lose body weight.