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

Diabetes Res Clin Pract. 2008 Jan;79(1):2-10. doi: 10.1016/j.diabres.2007.04.015. Epub 2007 Oct 23.

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

MeSH terms

  • Animal Feed
  • Animals
  • Diet*
  • Dietary Carbohydrates / pharmacology
  • Dietary Fats / pharmacology
  • Dietary Proteins / pharmacology
  • Eating
  • Fasting
  • Fatty Acids, Nonesterified / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Glucose / pharmacology
  • Hormones, Ectopic / genetics*
  • Intercellular Signaling Peptides and Proteins
  • Intestines / physiology*
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / genetics
  • Resistin / genetics*
  • Stearic Acids / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Dietary Carbohydrates
  • Dietary Fats
  • Dietary Proteins
  • Fatty Acids, Nonesterified
  • Hormones, Ectopic
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Resistin
  • Retn protein, mouse
  • Retnlb protein, mouse
  • Stearic Acids
  • Tumor Necrosis Factor-alpha
  • stearic acid
  • Glucose