Endothelial SR-B1 is dispensable for thermogenesis but promotes selective cholesterol uptake in brown adipose tissue.

In an interplay with parenchymal cells of metabolically active organs, such as heart and adipose tissues, vascular endothelial cells are important for the regulation of nutrient uptake and organ-specific energy metabolism. Based on high expression of the scavenger receptor class B type I (SR-B1) in capillary endothelial cells of white adipose tissue and brown adipose tissue (BAT), we proposed a functional role for this receptor in lipid handling and adaptive thermogenesis. To address this hypothesis, we generated mice with an endothelial-specific KO of SR-B1 and performed metabolic turnover and indirect calorimetry studies in response to environmental cues, such as cold exposure and high-fat diet feeding. Compared with control littermates, endothelial-specific SR-B1 KO mice had substantially lower SR-B1 mRNA and protein levels in heart, skeletal muscle, BAT, and white adipose tissue but not in liver, indicating that SR-B1 is primarily expressed by endothelial cells in peripheral organs. We did not detect major differences in gene expression of thermogenic and lipid-handling genes, energy expenditure assessed by indirect calorimetry, or clearance of metabolic tracers for glucose and triglycerides between endothelial SR-B1 KO mice and controls under basal conditions, thermogenic activation, or high-fat diet feeding. However, consistent with the importance of SR-B1 expression by hepatocytes for HDL metabolism, mice lacking endothelial SR-B1 had lower selective cholesterol uptake in the heart and BAT compared with control littermates. We conclude that endothelial SR-B1 is not essential for adaptive thermogenesis and handling of triglyceride-rich lipoproteins, but it is involved in regulating cholesterol homeostasis in the heart and BAT.