Regulation of gut-derived resistin-like molecule β expression by nutrients

Resistin was initially identified as a protein, secreted by adipocytes, which inhibits insulin action and adipose differentiation. The three proteins homologous to resistin were identified and given the names resistin-like molecules (RELM) alpha, beta and gamma. Resistin and RELM alpha are abundantly expressed in adipose, but RELM beta and RELM gamma are secreted mainly from the gut. Since nutrient composition greatly affects insulin sensitivity, we investigated the regulatory effects of various nutritional factors in food on the expressions of resistin family proteins. First, mice were given diets with different nutritional compositions (high-carbohydrate, high-protein and high-fat) for 2 weeks. RELM beta mRNA expression in the intestines was markedly suppressed by the high-protein and high-carbohydrate diets, while slightly but not significantly upregulated by the high-fat diet. In the epididymal fat, resistin expression was unchanged, while RELM alpha expression was markedly decreased by the high-carbohydrate diet. Taking into consideration that humans have neither RELM alpha nor RELM gamma, our subsequent studies focused on RELM beta expression. We used the human colon cancer cell line LS174T. Treatments with insulin and TNF alpha as well as stearic acid, a saturated free fatty acid, upregulated RELM beta expression, while D-glucose downregulated RELM beta. These results suggest RELM beta expression to be regulated directly by nutrients such as glucose and saturated free fatty acids including stearic acid, as well as by hormones including insulin and TNFa. These regulations may play an important role in the nutrient-associated induction of insulin resistance. (c) 2007 Elsevier Ireland Ltd. All rights reserved.