Monika Karczewska-Kupczewska1, Magdalena Stefanowicz1, Natalia Matulewicz1, Agnieszka Nikołajuk1, Marek Strączkowski1. 1. Department of Metabolic Diseases (M.K.-K., M.Ste., N.M., M.Str.), Medical University of Bialystok, PL-15-276 Bialystok, Poland; and Department of Prophylaxis of Metabolic Diseases (M.K.-K., A.N., M.Str.), Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, PL-10-748 Olsztyn, Poland.
Abstract
CONTEXT: The β-catenin-dependent Wnt signaling plays a role in adipogenesis, myogenesis, and glucose homeostasis. OBJECTIVE: The aim of this study was to assess adipose tissue and skeletal muscle expression of Wnt/β-catenin signaling genes in a young healthy population according to insulin sensitivity and its regulation by hyperinsulinemia and free fatty acids. DESIGN: We examined 117 male volunteers. The participants were divided into subgroups of high-insulin sensitivity (IS) and low-IS on the basis of a 2-hour euglycemic clamp. In 20 subjects, the clamp was prolonged to 6 hours. After 1 week, another 6-hour clamp, with Intralipid/heparin infusion, was performed. Tissue biopsies were performed before each clamp and after 6-hour clamps. Additionally, we collected muscle biopsies from another group of 16 male subjects for cell cultures. Myotubes were treated with insulin separately and in combination with palmitate. RESULTS: We found decreased adipose tissue WNT10B, FZD1/8, LRP5, DVL2, CTNN1B, TCF7L2, and AXIN2 and increased muscle WNT10B, FZD1/8, LRP6, DVL1, GSK3B, CTNNB1, TCF7L2, AXIN2, MYC, and CCND1 expression in the low-IS group. Hyperinsulinemia resulted in a decrease in adipose tissue FZD4, LRP5/6, TCF7L2, and AXIN2 and an increase in muscle FZD1/8, DVL1/2/3, TCF7L2, AXIN2, and MYC expression. These changes disappeared after free fatty acid elevation. In myotubes, insulin increased the expression of FZD1, DVL2, CTNNB1, and TCF7L2, whereas palmitate abolished these effects. CONCLUSIONS: The association of β-catenin-dependent Wnt signaling with insulin resistance is tissue specific. Observed changes might reflect a compensatory mechanism to increase muscle glucose uptake and to generate new fat cells in insulin-resistant conditions.
CONTEXT: The β-catenin-dependent Wnt signaling plays a role in adipogenesis, myogenesis, and glucose homeostasis. OBJECTIVE: The aim of this study was to assess adipose tissue and skeletal muscle expression of Wnt/β-catenin signaling genes in a young healthy population according to insulin sensitivity and its regulation by hyperinsulinemia and free fatty acids. DESIGN: We examined 117 male volunteers. The participants were divided into subgroups of high-insulin sensitivity (IS) and low-IS on the basis of a 2-hour euglycemic clamp. In 20 subjects, the clamp was prolonged to 6 hours. After 1 week, another 6-hour clamp, with Intralipid/heparin infusion, was performed. Tissue biopsies were performed before each clamp and after 6-hour clamps. Additionally, we collected muscle biopsies from another group of 16 male subjects for cell cultures. Myotubes were treated with insulin separately and in combination with palmitate. RESULTS: We found decreased adipose tissue WNT10B, FZD1/8, LRP5, DVL2, CTNN1B, TCF7L2, and AXIN2 and increased muscle WNT10B, FZD1/8, LRP6, DVL1, GSK3B, CTNNB1, TCF7L2, AXIN2, MYC, and CCND1 expression in the low-IS group. Hyperinsulinemia resulted in a decrease in adipose tissue FZD4, LRP5/6, TCF7L2, and AXIN2 and an increase in muscle FZD1/8, DVL1/2/3, TCF7L2, AXIN2, and MYC expression. These changes disappeared after free fatty acid elevation. In myotubes, insulin increased the expression of FZD1, DVL2, CTNNB1, and TCF7L2, whereas palmitate abolished these effects. CONCLUSIONS: The association of β-catenin-dependent Wnt signaling with insulin resistance is tissue specific. Observed changes might reflect a compensatory mechanism to increase muscle glucose uptake and to generate new fat cells in insulin-resistant conditions.
Authors: Ean G Phillips; Luke A Beggs; Fan Ye; Christine F Conover; Darren T Beck; Dana M Otzel; Payal Ghosh; Anna C F Bassit; Stephen E Borst; Joshua F Yarrow Journal: PLoS One Date: 2018-03-26 Impact factor: 3.240