Wnt Signaling Genes in Adipose Tissue and Skeletal Muscle of Humans With Different Degrees of Insulin Sensitivity

• Published in: The journal of clinical endocrinology and metabolism Vol. 101; no. 8; pp. 3079 - 3087
• Main Authors: Karczewska-Kupczewska, Monika, Stefanowicz, Magdalena, Matulewicz, Natalia, Nikołajuk, Agnieszka, Strączkowski, Marek
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.08.2016; Copyright by The Endocrine Society
• Subjects: Adipocytes; Adipogenesis; Adipogenesis - genetics; Adipose tissue; Adipose Tissue - metabolism; Adolescent; Adult; Biopsy; Body fat; Dishevelled protein; Fatty acids; Gene Expression Profiling; Gene regulation; Glucose Clamp Technique; Heparin; Homeostasis; Humans; Hyperinsulinemia; Insulin resistance; Insulin Resistance - genetics; LRP5 protein; Male; Muscle Development - genetics; Muscle, Skeletal - metabolism; Musculoskeletal system; Myc protein; Myogenesis; Myotubes; Palmitic acid; Population studies; Skeletal muscle; Transcriptome; Wnt protein; Wnt Signaling Pathway - genetics; Young Adult; β-Catenin
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2016-1594

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.The expression of Wnt signaling genes is decreased in adipose tissue and increased in skeletal muscle of subjects with low insulin sensitivity and is differentially regulated by hyperinsulinemia.