CD47 deficiency protects mice from diet-induced obesity and improves whole body glucose tolerance and insulin sensitivity.
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.
Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536; Lexington Veterans Affairs Medical Center, Lexington, KY.
Hasiyeti
H
Maimaitiyiming
Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536; Lexington Veterans Affairs Medical Center, Lexington, KY.
Heather
H
Norman
Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536; Lexington Veterans Affairs Medical Center, Lexington, KY.
Qi
Q
Zhou
Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536; Lexington Veterans Affairs Medical Center, Lexington, KY.
Shuxia
S
Wang
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D051928:CD47 Antigen / Q000378:metabolism*; D004041:Dietary Fats / Q000009:adverse effects*; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D051379:Mice; D009765:Obesity / Q000378:metabolism* / Q000517:prevention & control; D019700:Thrombospondin 1 / Q000378:metabolism*
D001786:Blood Glucose; D051928:CD47 Antigen; C497895:Cd47 protein, mouse; D004041:Dietary Fats; D019700:Thrombospondin 1; C585483:Thbs1 protein, mouse