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The Gravitostat Regulates Fat Mass in Obese Male Mice While Leptin Regulates Fat Mass in Lean Male Mice

Journal article
Authors Claes Ohlsson
Daniel Hägg
Fredrik Hammarhjelm
Adria Gasull
Jakob Bellman
Sara H Windahl
Vilborg Palsdottir
John-Olov Jansson
Published in Endocrinology
Volume 159
Issue 7
Pages 2676-2682
ISSN 0013-7227
Publication year 2018
Published at Institute of Neuroscience and Physiology, Department of Physiology
Institute of Medicine
Centre for Bone and Arthritis Research
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Pages 2676-2682
Language en
Keywords recombinant leptin, weight, resistance, hypothalamus, signal, rna, Endocrinology & Metabolism, ates of america, v115, p427
Subject categories Endocrinology


Leptin has been the only known homeostatic regulator of fat mass, but we recently found evidence for a second one, named the gravitostat. In the current study, we compared the effects of leptin and increased loading (gravitostat stimulation) on fat mass in mice with different levels of body weight (lean, overweight, and obese). 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 for 4 and 8 weeks, respectively. The maximum effect of leptin on body weight and fat mass was obtained already at < 44 ng/mL of serum leptin. Increased loading using intraperitoneal capsules with different weights decreased body weight in overweight and obese mice. Although the implantation of an empty capsule reduced the body weight in lean mice, only a nonsignificant tendency of a specific effect of increased loading was observed in the lean mice. 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. We propose that activation of the gravitostat primarily protects against obesity, whereas low levels of leptin protect against undernutrition.

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