Mechanisms that enhance energy expenditure are attractive therapeutic targets for obesity. Previously we have demonstrated that mice lacking cd47 are leaner, exhibit increased energy expenditure, and are protected against diet-induced obesity. In this study, we further defined the physiological role of cd47 deficiency in regulating mitochondrial function and energy expenditure in both white and brown adipose tissue. We observed that cd47 deficient mice (under normal chow diet) had comparable amount of white fat mass but reduced white adipocyte size as compared to wild-type mice. Subsequent ex vivo and in vitro studies suggest enhanced lipolysis, and not impaired lipogenesis or energy utilization, contributes to this phenotype. In contrast to white adipose tissue, there were no obvious morphological differences in brown adipose tissue between wild-type and knockout mice. However, mitochondria isolated from brown fat of cd47 deficient mice had significantly higher rates of free fatty acid-mediated uncoupling. This suggests that enhanced fuel availability via white adipose tissue lipolysis may perpetuate elevated brown adipose tissue energy expenditure and contributes to the lean phenotype observed in cd47 deficient mice.
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This work was supported by the Department of Veterans Affairs Merit Review Award (BX004252, to S.W.), the National Institutes of Health (NIH) Grant (DK098176, to S.W.), an Institutional Development Award (IDeA) (P30 GM127211), University of Kentucky-CARES grant (P30 ES026529) and the Redox Metabolism Shared Resources of the University of Kentucky Markey Cancer Center (P30 CA177558).
Norman-Burgdolf, Heather; Li, Dong; Sullivan, Patrick G.; and Wang, Shuxia, "CD47 Differentially Regulates White and Brown Fat Function" (2020). Pharmacology and Nutritional Sciences Faculty Publications. 117.