Vitamin D3 affects browning of white adipocytes by regulating autophagy via PI3K/Akt/mTOR/p53 signaling in vitro and in vivo

Promoting brown fat-like phenotype in white adipose tissue has been a promising strategy for the treatment of obesity. Vitamin D3 (VD3) has been indicated to affect differentiation of white and brown adipocytes. Nevertheless, its potential mechanism involved in obesity development is unclear. Oil red O staining was utilized to detect lipid formation in 3T3-L1 adipocytes. CKK-8 assay was used for measurement of cell viability. RT-qPCR and western blotting were implemented for expression detection of markers for white adipocyte browning, autophagy- and PI3K/Akt/mTOR/p53 signaling-associated proteins. Immunofluorescence staining was conducted for assessment of autophagy. An obese mouse model was established by high-fat VD deficient diet. VD3 suppressed lipid formation in 3T3-L1 adipocytes. VD3 downregulated markers for white adipocyte browning (PPAR-γ, PGC-1α, UCP1), enhanced autophagy, activated p53 signaling and inactivated PI3K/Akt/mTOR signaling in 3T3-L1 adipocytes and HF-VDD-induced mice. VD3 suppressed HF-VDD-induced weight gain in mice. VD3 inhibits the expression of markers for white adipocyte browning in vitro and in vivo by enhancing autophagy and regulating PI3K/Akt/mTOR/p53 signaling pathway.