Wntless represses brown adipose tissue differentiation and energy expenditure

Abstract

Objective To explore the effect of Wntless (Wls)-mediated Wnt signaling on the development and energy metabolism of brown adipose tissue (BAT). Methods BAT-specific Wls knockout (WlsMyf5Δ/Δ) mice were generated by Cre-loxP system. The differentiations of BAT in WlsMyf5Δ/Δ knockout mice and Wlsfl/fl control mice were analyzed by histological morphology, immunohistochemistry, real-time PCR, and Western blot. After stromal vascular fraction (SVF) cells in BAT were induced to differentiate, oil red O staining, real-time PCR, and cell respiration experiments were performed for analyzing in-vitro cell differentiation and oxygen consumption. The energy metabolism of mice was monitored by rectal temperature, oxygen consumption rate in BAT, and energy expenditure. The adiposity of mice was evaluated by NMR while the glucose metabolism was analyzed by the glucose and insulin tolerance tests. Results The WlsMyf5Δ/Δ knockout mice appeared smaller body size, lower weight, higher percentage of lean fat, lower size of BAT, with higher body temperature on the back as compared to Wlsfl/fl control mice. The differentiation and thermogenesis of BAT in Wls-deficient mice were relatively augmented, along with an increase in Ucp1 mRNA and protein expressions. SVF cells from BAT in WlsMyf5Δ/Δ knockout mice revealed enhanced brown differentiation. Adiposity was decreased and glucose metabolic capacity was enhanced in the WlsMyf5Δ/Δ knockout mice, without significant change in oxygen consumption of the whole body. Conclusion Wls-mediated Wnt signaling decreases the thermogenesis and glucose metabolism of BAT by suppressing its differentiation. Key words: Wnt signaling pathway; Wntless gene; Brown adipose tissue