Absence of CD47 maintains brown fat thermogenic capacity and protects mice from aging-related obesity and metabolic disorder

Brown and beige adipocytes burn energy to produce heat and could serve as a therapeutic target to counteract metabolic diseases including obesity and type 2 diabetes. Aging is associated with reduced brown fat mass and thermogenic capacity and a risk factor for metabolic diseases. Our previous studies implicated a role for CD47 in regulating brown fat function and energy balance in young adult animals. In this study, we further determined its role in natural aging related metabolic disorders. The results demonstrated that aged CD47 deficient mice (under normal chow diet) had reduced body weight and fat mass, and improved glucose tolerance as compared to aged wild type (WT) mice. Indirect calorimetry result showed that food intake and total activity were comparable between two genotypes. However, CD47 deficient mice had increased energy expenditure and better cold tolerance, accompanied by increased white adipose tissue browning and well-maintained juvenile morphology of brown adipose tissue (BAT). Moreover, transcriptome (RNA-seq) and pathway enrichment analysis revealed that BAT from aged CD47 deficient mice had upregulated genes involving in mitochondria oxidative phosphor-ylation, thermogenesis, fatty acid metabolism, and valine, leucine and isoleucine (BCAA) degradation, indicating the activated BAT status in aged CD47 deficient mice. Collectively, these data suggest that blocking CD47 signaling protects mice from natural aging-associated obesity and glucose intolerance, partially though activation and expansion of the thermogenic machinery, further supporting that CD47 maybe a potential target for aging related metabolic disorder. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

The study showed that aged CD47 deficient mice had reduced body weight and fat mass, improved glucose tolerance, increased energy expenditure, and better cold tolerance compared to aged wild type mice. Transcriptome analysis revealed upregulated genes related to mitochondrial function, thermogenesis, and fatty acid metabolism in the brown adipose tissue of CD47 deficient mice, indicating an activated status of the brown fat tissue.