CD47 antisense oligonucleotide treatment attenuates obesity and its-associated metabolic dysfunction

Abstract

Abstract Previous study from our lab has revealed a new role of CD47 in regulating adipose tissue function, energy homeostasis and the development of obesity and metabolic disease in CD47 deficient mice. In this study, the therapeutic potential of an antisense oligonucleotide (ASO) targeting to CD47 in obesity and its-associated complications was determined in two obese mouse models (diet induced and genetic models). In diet induced obesity, male C57BL6 mice were fed with high fat (HF) diet to induce obesity and then treated with CD47ASO or control ASO for 8 weeks. In genetic obese mouse model, male six-week old ob/ob mice were treated with ASOs for 9 weeks. We found that CD47ASO treatment reduced HF diet-induced weight gain, decreased fat mass, prevented dyslipidemia, and improved glucose tolerance. These changes were accompanied by reduced inflammation in white adipose tissue and decreased hepatic steatosis. This protection was also seen in CD47ASO treated ob/ob mice. Mechanistically, CD47ASO treatment increased mice physical activity and energy expenditure, contributing to weight loss and improved metabolic outcomes in obese mice. Collectively, these findings suggest that CD47ASO might serve as a new treatment option for obesity and its-associated metabolic complications.