Vanadium-protein complex inhibits human adipocyte differentiation through the activation of β-catenin and LKB1/AMPK signaling pathway

Abstract

Obesity is a common disease over the world and is tightly associated with diabetes mellitus, cardiovascular and cancer disease. Although our previous study showed that the synthetic vanadium-protein (V-P) complex had a better effect on antioxidant and antidiabetic, the relative molecular mechanisms are still entirely unknown. Hence, we investigated the effect of the synthetic V-P complex on adipocyte differentiation (adipogenesis) using human preadipocytes to clarify its molecular mechanisms of action. The primary human preadipocytes were cultured with and without V-P complex during adipocyte differentiation. The cell proliferation, lipid accumulation, and the protein expression of transcription factors and related enzymes were determined for the differentiated human preadipocytes. In this study, the 20 μg/mL of V-P complex reduced the lipid and triglyceride (TG) content by 74.47 and 57.39% (p < 0.05), respectively, and down-regulated the protein expressions of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer-binding protein alpha (C/ EBPα), sterol regulatory element-binding protein 1 (SREBP-1) and fatty acid synthase (FAS). Additionally, the V-P complex significantly up-regulated the protein levels of total βcatenin (t-β-catenin), nuclear β-catenin (n-β-catenin), phosphorylated adenosine monophosphate-activated protein kinase alpha (p-AMPKα) and liver kinase B1 (p-LKB1). These showed that the inhibitory effect of V-P complex on human adipogenesis was mediated by activating Wnt/β-catenin and LKB1/AMPK-dependent signaling pathway. Therefore, the synthetic V-P complex could be considered as a candidate for prevention and treatment of obesity.

Trace Element and Mineral Levels in Serum, Hair, and Urine of Obese Women in Relation to Body Composition, Blood Pressure, Lipid Profile, and Insulin Resistance

“…At the same time, our previous experimental [ 34 ] and human [ 28 ] studies demonstrated an inverse association between V levels and obesity. Correspondingly, V supplementation was shown to modulate adipogenesis [ 35 ], thus being indicative of its potential antiobesity effects [ 36 ].…”

The Influence of Organic Vanadium Complexes on an Antioxidant Profile in Adipose Tissue in Wistar Rats

“…Likewise, the studies by Zhang et al [ 49 ] showed that vanadium complexes with concentrations below 20 µg/mL have low cytotoxicity. During an excessive supply of nutrients, the growth of white adipose tissue (WAT) prevents ectopic fat accumulation by affecting the rate of differentiation to adipocytes in preadipocytes [ 50 ].…”

The Anti-Adiposity Mechanisms of Ampelopsin and Vine Tea Extract in High Fat Diet and Alcohol-Induced Fatty Liver Mouse Models

“…The γ isoform exists in all tissues, is predominantly expressed in adipose tissue, and is essential for the differentiation and function of adipocytes [ 27 , 28 ]. A previous study reported that PPARγ was the most highly expressed and necessary in adipocytes for differentiation and is regarded as a master regulator of adipogenesis and a key regulator of gene expression in matured adipocytes [ 29 , 30 , 31 ]. Besides these, recently, lots of experiments related to obesity in whole-body PPARα − deficient mice (PPARα −/− ) and in mice lacking PPARα only in hepatocytes (PPARα hep−/− ) were performed.…”