Scavenger receptor class B type I is required for efficient glucose uptake and metabolic homeostasis in adipocytes. bioRxiv 2023 Aug 22
Date
09/04/2023Pubmed ID
37662321Pubmed Central ID
PMC10473602DOI
10.1101/2023.08.21.554190Abstract
Obesity is a worldwide epidemic and places individuals at a higher risk for developing comorbidities that include cardiovascular disease and type 2 diabetes. Adipose tissue contains adipocytes that are responsible for lipid metabolism and reducing misdirected lipid storage. Adipocytes facilitate this process through insulin-mediated uptake of glucose and its subsequent metabolism into triglycerides for storage. During obesity, adipocytes become insulin resistant and have a reduced ability to mediate glucose import, thus resulting in whole-body metabolic dysfunction. Scavenger receptor class B type I (SR-BI) has been implicated in glucose uptake in skeletal muscle and adipocytes via its native ligands, apolipoprotein A-1 and high-density lipoproteins. Further, SR-BI translocation to the cell surface in adipocytes is sensitive to insulin stimulation. Using adipocytes differentiated from ear mesenchymal stem cells isolated from wild-type and SR-BI knockout (SR-BI -/- ) mice as our model system, we tested the hypothesis that SR-BI is required for insulin-mediated glucose uptake and regulation of energy balance in adipocytes. We demonstrated that loss of SR-BI in adipocytes resulted in inefficient glucose uptake regardless of cell surface expression levels of glucose transporter 4 compared to WT adipocytes. We also observed reduced glycolytic capacity, increased lipid biosynthesis, and dysregulated expression of lipid metabolism genes in SR-BI -/- adipocytes compared to WT adipocytes. These results partially support our hypothesis and suggest a novel role for SR-BI in glucose uptake and metabolic homeostasis in adipocytes.
Author List
Knaack DA, Chang J, Thomas MJ, Sorci-Thomas MG, Chen Y, Sahoo DAuthors
Daisy Sahoo PhD Dean, Professor in the Medicine department at Medical College of WisconsinMary Sorci Thomas PhD Professor in the Medicine department at Medical College of Wisconsin