Quantification of Bone Fatty Acid Metabolism and Its Regulation by Adipocyte Lipoprotein Lipase.

Alexander Bartelt,Joerg Heeren,Friederike Behler-Janbeck,Andreas Niemeier,Brigitte Müller,Rudolph Reimer,Klaus Tödter,Ludger Scheja,Till Koehne

doi:10.3390/ijms18061264

Abstract

Adipocytes are master regulators of energy homeostasis. Although the contributions of classical brown and white adipose tissue (BAT and WAT, respectively) to glucose and fatty acid metabolism are well characterized, the metabolic role of adipocytes in bone marrow remains largely unclear. Here, we quantify bone fatty acid metabolism and its contribution to systemic nutrient handling in mice. Whereas in parts of the skeleton the specific amount of nutrients taken-up from the circulation was lower than in other metabolically active tissues such as BAT or liver, the overall contribution of the skeleton as a whole organ was remarkable, placing it among the top organs involved in systemic glucose as well as fatty acid clearance. We show that there are considerable site-specific variations in bone marrow fatty acid composition throughout the skeleton and that, especially in the tibia, marrow fatty acid profiles resemble classical BAT and WAT. Using a mouse model lacking lipoprotein lipase (LPL), a master regulator of plasma lipid turnover specifically in adipocytes, we show that impaired fatty acid flux leads to reduced amounts of dietary essential fatty acids while there was a profound increase in de novo produced fatty acids in both bone marrow and cortical bone. Notably, these changes in fatty acid profiles were not associated with any gross skeletal phenotype. These results identify LPL as an important regulator of fatty acid transport to skeletal compartments and demonstrate an intricate functional link between systemic and skeletal fatty acid and glucose metabolism.

Highlights

The adipose organ is a highly dynamic tissue comprising white, brown and beige adipocytes [1]
Using a mouse model lacking lipoprotein lipase (LPL), a master regulator of plasma lipid turnover in adipocytes, we show that impaired fatty acid flux leads to reduced amounts of dietary essential fatty acids while there was a profound increase in de novo produced fatty acids in both bone marrow and cortical bone
Neither whether certain types of fatty acids impact on bone homeostasis nor the identity of their cellular source is well understood. ω-3 fatty acids, especially docosahexaenoic acid (DHA, C22:6n-3), which is abundant in fish oil, have been demonstrated to confer beneficial effects on the skeleton: ω-3 supplementation leads to increased bone mineral density (BMD) in different locations in mice [28], attenuates ovariectomy-induced bone loss [29,30] and in general is positively correlated to bone mineral content in the femur of rats [31]

Summary

Introduction

The adipose organ is a highly dynamic tissue comprising white, brown and beige adipocytes [1]. Ω-3 fatty acids, especially docosahexaenoic acid (DHA, C22:6n-3), which is abundant in fish oil, have been demonstrated to confer beneficial effects on the skeleton: ω-3 supplementation leads to increased bone mineral density (BMD) in different locations in mice [28], attenuates ovariectomy-induced bone loss [29,30] and in general is positively correlated to bone mineral content in the femur of rats [31] These observations can be attributed to specific inhibitory effects of DHA on osteoclasts differentiation as well as activity and on the systemic inflammatory milieu [28,30,32,33]. A class of fatty acid-derivatives, namely N-acyl amides have been implicated in bone remodeling

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Results

Conclusion