Lack of serum albumin improves insulin sensitivity in both male and female mice

Abstract

Insulin resistance is a global health problem. It has been shown that free fatty acids (FFA) play a major role in insulin resistance. Albumin acts as main fatty acid binding protein in blood. To improve understanding of the role of FFA in insulin resistance, we aimed to determine whether lack of serum albumin and the associated suppression of plasma FFA concentration would improve insulin sensitivity in albumin knockout mice compared to wild type mice. Male and female homozygous albumin knockout mice and C57BL/6J wild‐type controls, each fed a chow diet, were studied at 6‐8 weeks of age. Glucose tolerance test, insulin tolerance test, tissue analyses, and plasma proteomics were performed. In both sexes of albumin knockout mice compared to wild‐type mice, we observed lower levels of hepatic diacylglycerol content, as well as lower blood glucose during glucose tolerance test and insulin tolerance test (P < 0.05). The level of mRNA measurement showed higher expression of adiponectin, lipoprotein lipase, diacylglycerol acyltransferase‐1 and ‐2, and glucose transporter‐4 in adipose tissue, as well as lower hepatic perilipin‐2 expression (P<0.05). In agreement with adipose mRNA level analysis, plasma proteomics indicated that circulating adiponectin concentration was higher in albumin knockout compared to wild‐type mice (P<0.05). The results indicate an important role of albumin and plasma FFA concentration in lipid and glucose metabolism. We suggest that the lower plasma FFA concentration in albumin knockout mice compared to wild‐type mice leads to less hepatic diacylglycerol accumulation, and the lower level of this lipotoxic compound may contribute to the enhanced insulin sensitivity.