CD47 is a transmembrane protein with several functions including self-recognition, immune cell communication, and cell signaling. Although it has been extensively studied in cancer and ischemia, CD47 function in obesity has never been explored. In this study, we utilized CD47 deficient mice in a high-fat diet induced obesity model to study for the first time whether CD47 plays a role in the development of obesity and metabolic complications. Male CD47 deficient and wild type (WT) control mice were fed with either low fat (LF) or high fat (HF) diets for 16 weeks. Interestingly, we found that CD47 deficient mice were protected from HF diet-induced obesity displaying decreased weight gain and reduced adiposity. This led to decreased MCP1/CCR2 dependent macrophage infiltration into adipose tissue and reduced inflammation, resulting in improved glucose tolerance and insulin sensitivity. In addition, CD47 deficiency stimulated the expression of UCP1 and carnitine palmitoyltransferase 1b (CPT1b) levels in brown adipose tissue, leading to increased lipid utilization and heat production. This contributes to the increased energy utilization and reduced adiposity observed in these mice. Taken together, these data revealed a novel role for CD47 in the development of obesity and its related metabolic complications.
Digital Object Identifier (DOI)
This study was supported in part by the Department of Veterans Affairs Merit Review Award (to S. Wang), the National Institutes of Health (NIH) Grant R01 DK081555 and DK098176 (to S. Wang), NIH Training Grant DK07778 (to H. Norman), and a COBRE grant P20GM103527-06.
Maimaitiyiming, Hasiyeti; Norman, Heather; Zhou, Qi; and Wang, Shuxia, "CD47 Deficiency Protects Mice from Diet-Induced Obesity and Improves Whole Body Glucose Tolerance and Insulin Sensitivity" (2015). Pharmacology and Nutritional Sciences Faculty Publications. 30.
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Figure 1: CD47 deficient mice were protected from high fat diet-induced obesity.
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Figure 2: HF-fed CD47 deficient mice displayed reduced systemic inflammation compared to HF-fed wild type controls.
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Figure 3: HF-fed CD47 deficient mice had decreased adipose tissue macrophage infiltration and inflammation.
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Figure 4: CD47 deficiency prevents lipid accumulation in liver after HF diet feeding.
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Figure 5: HF-fed CD47 deficient mice had improved glucose tolerance and insulin sensitivity.
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Figure 6: Energy metabolism in WT and CD47 deficient mice under either LF or HF feeding conditions.
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Figure 7: Metabolic gene expression in skeletal muscle from LF or HF feeding WT or CD47 deficient mice.
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Figure 8: Morphology and metabolic gene expression in brown adipose tissue from LF or HF feeding WT or CD47 deficient mice.
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Figure 9: cGMP or PKG signaling in brown adipose tissue and skeletal muscle from LF or HF feeding WT or CD47 deficient mice.