Fucosterol inhibits adipogenesis through the activation of AMPK and Wnt/β-catenin signaling pathways

Abstract

Fucosterol is a sterol constituent primarily derived from brown algae. Recently, the antiadipogenic effect of fucosterol has been reported; however, its molecular mechanism remains to be studied. Fucosterol effectively upregulated the phosphorylations of both adenosine monophosphate (AMP)-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), and downregulated the expression levels of lipogenesis-related factors. Moreover, fucosterol activated the major components of the Wnt/β-catenin signaling pathway, including β-catenin, disheveled 2 (DVL2), and cyclin D1 (CCND1), whereas it inactivated glycogen synthase kinase 3β (p-GSK3β) by stimulating its phosphorylation. In the presence or absence of fucosterol, the adipogenic transcriptional factors [peroxisome proliferator activated-receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and sterol regulatory element binding protein-1c (SREBP-1c)] were upregulated by the inhibition of AMPK by compound C or the knockdown of β-catenin by siRNA. Overall, these data demonstrate that fucosterol prevents adipogenesis by mediating both AMPK- and Wnt/β-catenin-signaling pathways.

2,6-Dimethoxy-1,4-benzoquinone Inhibits 3T3-L1 Adipocyte Differentiation via Regulation of AMPK and mTORC1

“…The modulation of AMPK can inhibit the progression of adipogenic differentiation. Fucosterol derived from brown algae suppresses adipogenesis via AMPK activation [40], while Arctigenin found in Arctii Fructus suppresses adipogenic differentiation via the activation of AMPK and reduces obesity in high-fat diet-induced obese mice [41]. We observed that DMBQ increases phosphorylation of AMPK while downregulating mature SREBP-1 and PPARγ expression in 3T3-L1 adipocytes.…”

Attenuation of lipid accumulation in Bel‐7402 cells through ADPN/AMPKα signaling stimulated by Fructus rosae laxae extract

“…In the ELISA results, the expression of ADPN was increased in each group compared with that in the model group, indicating that FRLE can activate the AMPKα phosphorylation pathway by increasing the expression of ADPN. After the AMPKα phosphorylation level was increased, the downstream molecule ACC phosphorylation pathway was also activated, and the ACC pathway was inhibited (Song et al., 2017). Meanwhile, the expression of related downstream lipid synthesis indexes, such as SREBP‐1c, was inhibited (Zhang et al., 2017).…”

Brown Seaweeds for the Management of Metabolic Syndrome and Associated Diseases

“…Mechanism of action: Several studies have investigated both in vitro and in vivo the potential health benefits and the underlying pharmacological mechanisms of phytosterols, beyond the well-known cholesterol-lowering effect, obtained by competition with cholesterol upon intestinal absorption [ 119 ]. The phytosterol fucosterol exerts hepatoprotective, anti-obesity, anti-diabetic, and antihypertensive activities [ 46 , 78 , 79 ]. Moreover, it has been demonstrated that it inhibits adipogenesis and adipocytes differentiation by diverse molecular mechanisms [ 78 , 79 , 80 ].…”

“…The phytosterol fucosterol exerts hepatoprotective, anti-obesity, anti-diabetic, and antihypertensive activities [ 46 , 78 , 79 ]. Moreover, it has been demonstrated that it inhibits adipogenesis and adipocytes differentiation by diverse molecular mechanisms [ 78 , 79 , 80 ]. In particular, the downregulation of Peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) leads to a reduction in lipid accumulation inside adipocytes [ 79 ].…”