Albiflorin ameliorates obesity by inducing thermogenic genes via AMPK and PI3K/AKT in vivo and in vitro

ObjectiveBrown adipose tissue (BAT) activation has been identified as a possible target to treat obesity and to protect against metabolic diseases by increasing energy consumption. We explored whether albiflorin (AF), a natural compound, could contribute to lowering the high risk of obesity with BAT and primary brown preadipocytes in vivo and in vitro.Materials/MethodsHuman adipose tissue-derived mesenchymal stem cells (hAMSCs) were cultured with adipogenic differentiation media with or without AF. Male C57BL/6J mice (n = 5 per group) were fed a high-fat diet (HFD) for six weeks with or without AF. Brown preadipocytes from the interscapular BAT of mice were cultured with or without AF.ResultsIn white adipogenic differentiation of hAMSCs, AF treatment significantly reduced the formation of lipid droplets and the expression of adipogenesis-related genes. In HFD-induced obese C57BL/6J mice, AF treatment significantly reduced body weight gain as well as the weights of the white adipose tissue, liver and spleen. Furthermore, AF induced the expression of genes involved in thermogenic function in BAT. In primary brown adipocytes, AF effectively stimulated the expressions of thermogenic genes and markedly up-regulated the AMP-activated protein kinase (AMPK) signaling pathway. Pretreatment with phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 nullified the induction of the thermogenic genes by AF in primary brown adipocytes. Moreover, AF activated beige cell marker genes induced by the pharmacological activation of peroxisome proliferator-activated receptor γ in hAMSCs.ConclusionThis study shows that AF prevents the development of obesity in hAMSCs and mice fed an HFD and that it is also capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes by AMPK and PI3K/AKT.