Berberine Alleviates Olanzapine-Induced Adipogenesis via the AMPKα–SREBP Pathway in 3T3-L1 Cells

Abstract

The aim of this study was to investigate the mechanisms underlying the inhibitory effects of berberine (BBR) on olanzapine (OLZ)-induced adipogenesis in a well-replicated 3T3-L1 cell model. Oil-Red-O (ORO) staining showed that BBR significantly decreased OLZ-induced adipogenesis. Co-treatment with OLZ and BBR decreased the accumulation of triglyceride (TG) and total cholesterol (TC) by 55.58% ± 3.65% and 49.84% ± 8.31%, respectively, in 3T3-L1 adipocytes accompanied by reduced expression of Sterol regulatory element binding proteins 1 (SREBP1), fatty acid synthase (FAS), peroxisome proliferator activated receptor-γ (PPARγ), SREBP2, low-density lipoprotein receptor (LDLR), and hydroxymethylglutaryl-coenzyme A reductase (HMGR) genes compared with OLZ alone. Consistently, the co-treatment downregulated protein levels of SREBP1, SREBP2, and LDLR by 57.71% ± 9.42%, 73.05% ± 11.82%, and 59.46% ± 9.91%, respectively. In addition, co-treatment reversed the phosphorylation level of AMP-activated protein kinase-α (AMPKα), which was reduced by OLZ, determined via the ratio of pAMPKα:AMPKα (94.1%) compared with OLZ alone. The results showed that BBR may prevent lipid metabolism disorders caused by OLZ by reversing the degree of SREBP pathway upregulated and the phosphorylation of AMPKα downregulated. Collectively, these results indicated that BBR could be used as a potential adjuvant to prevent dyslipidemia and obesity caused by the use of second-generation antipsychotic medication.

Berberine Inhibits Adipogenesis in Porcine Adipocytes via AMP‐Activated Protein Kinase‐Dependent and ‐Independent Mechanisms

“…BBR, berberine remarkable antiadipogenic activity in porcine adipocytes. This observation was consistent with previous findings in 3 T3-L1 adipocytes (Choi et al, 2014;Jin et al, 2016;Li et al, 2016;Zhang et al, 2015).…”

“…5c). These results demonstrate that the AMPK signaling pathway mediates berberine-induced suppression of the transcriptional cascades triggered by SREBF1 and PPARγ2 in porcine adipocytes, which are compatible with previous reports that AMPK activation reduces the levels of PPARγ2 and SREBF1 protein, as well as their transcriptional activity in 3T3-L1 adipocytes (Jang et al, 2017;Jiang et al, 2012;Li et al, 2016). Furthermore, as shown in Fig.…”

“…c, d), indicating that berberine inhibits adipogenesis in porcine adipocytes through the activation of AMPK signaling pathway. The results are supported by previous studies in 3 T3‐L1 adipocytes (Jiang et al, , ; Li et al, ). On the contrary, recent conflicting reports involving the role of AMPK in adipogenesis showed that suppressing AMPK activity with compound C, a specific AMPK inhibitor, resulted in a decreased lipid accumulation and protein level of the adipogenic marker gene Perilipin a in adipogenic‐induced C3H10T1/2 mouse mesenchymal stem cells (MSC) (Chen et al, ).…”

“…Combined with the reduced lipid accumulation in berberine-stimulated adipocytes (Fig. 1), these results indicate that berberine inhibits adipogenesis by downregulation of the aforementioned adipogenic genes in porcine adipocytes, which are supported by previous studies in 3T3-L1 adipocytes (Jang et al, 2017;Kim et al, 2004;Li et al, 2016;Zhang et al, 2015).…”

Curcumin Activates AMPK Pathway and Regulates Lipid Metabolism in Rats Following Prolonged Clozapine Exposure

“…The present study demonstrated that CLO treatment suppressed AMPK signaling, which is in line with the previous research showing that the phosphorylation of AMPK was inhibited following CLO exposure in both primary hepatocytes and mice liver (Oh et al, 2011 ). Additionally, a recent study also demonstrated that olanzapine treatment can inhibit AMPK signaling and activate SREBP pathway, resulting in exacerbated adipogenesis in a 3T3-L1 cell model, whereas co-treatment with berberine, a naturally occurring alkaloid, alleviates olanzapine-induced lipid accumulation via modulating AMPK-SREBP pathway (Li et al, 2016 ). Likewise, the preventive effect of betahistine against olanzapine-induced dyslipidemia, which has been repeatedly documented in both animals and schizophrenia patients, is also at least partly mediated by the hepatic AMPK-SREBP system (Xuemei et al, 2015 ).…”