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Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):427-432. doi: 10.1073/pnas.1715687114. Epub 2017 Dec 26.

Body weight homeostat that regulates fat mass independently of leptin in rats and mice.

Author information

1
Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE 405 30, Gothenburg, Sweden; joj@neuro.gu.se jgustafs@central.uh.edu Claes.Ohlsson@medic.gu.se.
2
Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, SE 405 30, Gothenburg, Sweden.
3
Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE 413 45, Gothenburg, Sweden.
4
Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE 413 45, Gothenburg, Sweden.
5
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216.
6
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109-2216.
7
Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, ON M5G 1X5, Toronto, Canada.
8
Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204 joj@neuro.gu.se jgustafs@central.uh.edu Claes.Ohlsson@medic.gu.se.
9
Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE 413 45, Gothenburg, Sweden; joj@neuro.gu.se jgustafs@central.uh.edu Claes.Ohlsson@medic.gu.se.

Abstract

Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat ("gravitostat") that regulates fat mass.

KEYWORDS:

diet-induced obesity; glucose metabolism; osteocytes; weight loss

Comment in

PMID:
29279372
PMCID:
PMC5777058
DOI:
10.1073/pnas.1715687114
[Indexed for MEDLINE]
Free PMC Article

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