Berberine Alleviates Olanzapine-Induced Adipogenesis via the AMPKα-SREBP Pathway in 3T3-L1 Cells.
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.
School of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China. anlan8934@email.swu.edu.cn.|Engineer Research Center of Chongqing Pharmaceutical Process and Quality Control, Chongqing 400715, China. anlan8934@email.swu.edu.cn.
Yanjie
Y
Li
School of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China. zxmqingting1219@163.com.|Engineer Research Center of Chongqing Pharmaceutical Process and Quality Control, Chongqing 400715, China. zxmqingting1219@163.com.
Xiaomin
X
Zhao
School of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China. fengxiyu1991858@163.com.|Engineer Research Center of Chongqing Pharmaceutical Process and Quality Control, Chongqing 400715, China. fengxiyu1991858@163.com.
Xiyu
X
Feng
School of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China. liuxm@swu.edu.cn.|Engineer Research Center of Chongqing Pharmaceutical Process and Quality Control, Chongqing 400715, China. liuxm@swu.edu.cn.
Xuemei
X
Liu
Antipsychotic Research Laboratory, School of Medicine, and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong 2522, NSW, Australia. chao@uow.edu.au.
Chao
C
Deng
School of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China. chhhu@swu.edu.cn.|Engineer Research Center of Chongqing Pharmaceutical Process and Quality Control, Chongqing 400715, China. chhhu@swu.edu.cn.
Chang-Hua
CH
Hu
D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D000818:Animals; D014150:Antipsychotic Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001569:Benzodiazepines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001599:Berberine / Q000494:pharmacology*; D002454:Cell Differentiation; D002784:Cholesterol / Q000096:biosynthesis; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent / Q000235:genetics / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D051379:Mice; D000077152:Olanzapine; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics* / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D014150:Antipsychotic Agents; D000960:Hypolipidemic Agents; D047495:PPAR gamma; D011973:Receptors, LDL; C497388:Srebf1 protein, mouse; C497391:Srebf2 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014280:Triglycerides; D001599:Berberine; D001569:Benzodiazepines; D002784:Cholesterol; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D054890:Fatty Acid Synthase, Type I; C548179:Prkaa1 protein, mouse; D055372:AMP-Activated Protein Kinases; D000077152:Olanzapine
3T3-L1 cells; AMPKα; SREBPs; adipogenesis; berberine; olanzapine