Abstract
Berardinelli-Seip congenital generalized lipodystrophy is associated with increased bone mass suggesting that fat tissue regulates the skeleton. Because there is little mechanistic information regarding this issue, we generated "fat-free" (FF) mice completely lacking visible visceral, subcutaneous and brown fat. Due to robust osteoblastic activity, trabecular and cortical bone volume is markedly enhanced in these animals. FF mice, like Berardinelli-Seip patients, are diabetic but normalization of glucose tolerance and significant reduction in circulating insulin fails to alter their skeletal phenotype. Importantly, the skeletal phenotype of FF mice is completely rescued by transplantation of adipocyte precursors or white or brown fat depots, indicating that adipocyte derived products regulate bone mass. Confirming such is the case, transplantation of fat derived from adiponectin and leptin double knockout mice, unlike that obtained from their WT counterparts, fails to normalize FF bone. These observations suggest a paucity of leptin and adiponectin may contribute to the increased bone mass of Berardinelli-Seip patients.
Highlights
The past decades have witnessed elegant studies of the relationship of energy metabolism and bone, concluding they are mutually regulatory
Berardinelli-Seip congenital generalized lipodystrophy is a human disorder associated with increased bone mass suggesting that fat, per se, regulates the skeleton
To test this hypothesis we generated a murine model of congenital generalized lipodystrophy in which both brown and white adipose tissue are entirely depleted during embryogenesis
Summary
The past decades have witnessed elegant studies of the relationship of energy metabolism and bone, concluding they are mutually regulatory By this scenario, selected adipokines influence skeletal mass by directly and indirectly targeting osteoblasts and osteoclasts [1,2,3,4]. While subcutaneous fat, residing predominantly in thighs and buttocks, correlates with enhanced bone mass, increased visceral fat, which characterizes the metabolic syndrome, is associated with osteoporosis [1,2,3, 6] Why this distinction occurs is, completely unknown nor is there mechanistic proof of a cause/effect relationship between fat and abundance of bone
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
