A novel lipocalin, LCN14, ameliorates hyperglycemia in diet-induced obese mice via reducing glycerol efflux from adipose tissue

Abstract

Adipose tissue is an active endocrine organ that plays important roles in regulating energy metabolism in various organs, and dysreguation of adipose tissue-derived hormones may contribute to the pathogenesis of diabetic complications. In this study we identified a novel adipokine, lipocalin 14 (LCN 14), whose circulating level and expression in white adipose tissues are severely reduced in both diet-induced and genetically diabetic mice. This study aims to investigate whether over-expression of LCN14 could alleviate hyperglycemia, glucose intolerance and insulin resistance in obese mice. Mice (C57/BL6N) were fed with either chow diet (STC) or high-fat diet (HFD) for 10 weeks, followed by infection with recombinant adeno-associated virus (rAAV) encoding LCN14, or eGFP as a control. Our findings suggest that over-expressing LCN14 could lead to elevate circulating level of LCN14, which increase in insulin sensitivity in major metabolic tissues, including liver, muscle and adipose tissues. Interestingly, over-expressing LCN14 can also lower serum glycerol level by reducing the glycerol efflux from adipose tissue, which limited the availability of glycerol for hepatic gluconeogenesis, and hence reversing hyperglycemia. Collectively, our results provided the first evidence that LCN14 is a novel adipokine involved in glucose metabolism. The deficiency of LCN14 in diet-induced obese mice may contribute to the development of hyperglycemia and insulin resistance. LCN14, therefore, represents a promising molecular target for the development of new tools for blood-glucose-lowering therapy.