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

Abstract 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) α, β and γ. Resistin and RELMα are abundantly expressed in adipose, but RELMβ and RELMγ 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. RELMβ 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 RELMα expression was markedly decreased by the high-carbohydrate diet. Taking into consideration that humans have neither RELMα nor RELMγ, our subsequent studies focused on RELMβ expression. We used the human colon cancer cell line LS174T. Treatments with insulin and TNFα as well as stearic acid, a saturated free fatty acid, upregulated RELMβ expression, while d -glucose downregulated RELMβ. These results suggest RELMβ 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 TNFα. These regulations may play an important role in the nutrient-associated induction of insulin resistance.