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

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.

SUBMITTER: Jansson JO

PROVIDER: S-EPMC5777058 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

Jansson John-Olov JO Palsdottir Vilborg V Hägg Daniel A DA Schéle Erik E Dickson Suzanne L SL Anesten Fredrik F Bake Tina T Montelius Mikael M Bellman Jakob J Johansson Maria E ME Cone Roger D RD Drucker Daniel J DJ Wu Jianyao J Aleksic Biljana B Törnqvist Anna E AE Sjögren Klara K Gustafsson Jan-Åke JÅ Windahl Sara H SH Ohlsson Claes C

Proceedings of the National Academy of Sciences of the United States of America 20171226 2

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 toler ...[more]

PMID: 29279372

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Project description:BackgroundLactobacillus extracts and supernatants have been used as probiotics in human and veterinary medicine for their ability to enhance wound healing and immunity. Previous data from our laboratory demonstrated that Lactobacillus supernatant (LS) stimulated wound healing, angiogenesis and proliferation of embryonic cells after topical application. This current study shows that LS after its administration into the cerebral ventricles of male rats exerts systemic effects.MethodsThe right lateral cerebral ventricle of young male rats was accessed through intracerebroventricular cannulation (ICV) under anesthesia and aseptic conditions. One group of control rats received saline solution, a second control group received 0.8 M lactic acid solution (to control for acidity of LS), and a third group received LS. The animals were sacrificed 12, 24, 48, 96 and 120 hours after the injection. Selected tissues were collected, fixed in 10% buffered formalin and used for immunohistochemistry and in situ hybridization. Other tissues were frozen and extracted for immunoblottingResultsLS-injected animals had a slight decrease in body weight when compared to their initial weight and to both control groups. Using immunohistochemistry and in situ hybridization leptin expression was studied in multiple brain sections and peripheral adipose tissue of control and LS-injected rats. Strong cytoplasmic stain was observed by both techniques in neurons of the cerebral cortex, thalamus, hypothalamus, hippocampus and, to lesser degree, in the cells of the choroid plexus in the LS-injected rats. Control animals demonstrated much less intense staining in neurons located in the same regions using immunohistochemistry and almost no staining with in situ hybridization technique. Adipose tissue exhibited slight presence of leptin in LS-treated animals. In contrast no immunohistochemical staining for GM-CSF and TNFalpha was observed in brains from control and treated rats. Western blotting showed mild increase in leptin and leptin receptors in intestines and retroperitoneal adipose tissues of LS-injected rats.ConclusionThis study demonstrates that direct administration of LS into rat CNS leads to a decrease in body weight of rats and an increase in the expression of leptin in specific areas of the brain and retroperitoneal adipose tissue.

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

Publications

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

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