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Increased bone mass in a mouse model with low fat mass.

Journal article
Authors Louise Grahnemo
Karin L. Gustafsson
Klara Sjögren
Petra Henning
Vikte Lionikaite
Antti Koskela
Juha Tuukkanen
Claes Ohlsson
Ingrid Wernstedt Asterholm
Marie Lagerquist
Published in American journal of physiology. Endocrinology and metabolism
Volume 315
Issue 6
Pages E1274-E1285
ISSN 1522-1555
Publication year 2018
Published at Institute of Neuroscience and Physiology, Department of Physiology
Centre for Bone and Arthritis Research
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Pages E1274-E1285
Language en
Links dx.doi.org/10.1152/ajpendo.00257.20...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Endocrinology

Abstract

Mice with impaired acute inflammatory responses within adipose tissue display reduced diet-induced fat mass gain associated with glucose intolerance and systemic inflammation. Therefore, acute adipose tissue inflammation is needed for a healthy expansion of adipose tissue. Because inflammatory disorders are associated with bone loss, we hypothesized that impaired acute adipose tissue inflammation leading to increased systemic inflammation results in a lower bone mass. To test this hypothesis, we used mice overexpressing an adenoviral protein complex - the receptor internalization and degradation (RID) complex that inhibits pro-inflammatory signaling - under the control of the aP2-promotor (RID tg mice), resulting in suppressed inflammatory signaling in adipocytes. As expected, RID tg mice had a lower high-fat diet-induced weight and fat mass gain and higher systemic inflammation than their littermate wild type controls. Contrary to our hypothesis, the RID tg mice had increased bone mass in long bones and vertebrae, affecting trabecular and cortical parameters, as well as improved humeral biomechanical properties. We did not find any differences in bone formation or resorption parameters as determined by histology or enzyme immunoassay. However, bone marrow adiposity, often negatively associated with bone mass, was decreased in male RID tg mice as determined by histological analysis of tibia. In conclusion, mice with reduced fat mass, due to impaired adipose tissue inflammation, have increased bone mass.

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