Role of the secretory protein neudesin in energy metabolism

Abstract

The epidemic of obesity has become a serious health challenge in both developed and developing countries. Since the identification of leptin, a secretory protein from the white adipose tissue, secretory proteins have become recognized as important regulators of energy metabolism. We previously identified neudesin as a novel secretory protein. We also showed that neudesin was strongly expressed in central the nervous system of embryonic and adult mice, and was expressed in various peripheral tissues of adult mice. Thus, in this review, we discuss the physiological roles of neudesin and focus on its involvement in energy metabolism. We generated neudesin knock-out (KO) mice, and showed that they were resistant to high-fat diet (HFD)-induced obesity. Neudesin KO mice were protected from HFD-induced insulin resistance and hepatic steatosis. Furthermore, neudesin KO mice showed increased energy expenditure due to enhanced sympathetic nervous activity (SNA). Thus, resistance to HFD-induced obesity in neudesin KO mice was the result of increased energy expenditure. Neudesin KO mice also showed increased heat production and fatty acid oxidation in the adipose tissue. These results suggest that neudesin might act on neurons and adipocytes to suppress SNA. In conclusion, we establish the role of neudesin as a supressor of energy expenditure via regulating SNA. Neudesin is a novel regulator of energy metabolism and might be a target for the treatment of obesity and obesity-related metabolic syndrome.