scholarly journals AMP-activated Protein Kinase Is Required for the Lipid-lowering Effect of Metformin in Insulin-resistant Human HepG2 Cells

2004 ◽  
Vol 279 (46) ◽  
pp. 47898-47905 ◽  
Author(s):  
Mengwei Zang ◽  
Adriana Zuccollo ◽  
Xiuyun Hou ◽  
Daisuke Nagata ◽  
Kenneth Walsh ◽  
...  
2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Hui-Kang Liu ◽  
Tzu-Min Hung ◽  
Hsiu-Chen Huang ◽  
I-Jung Lee ◽  
Chia-Chuan Chang ◽  
...  

Obesity and associated conditions, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are currently a worldwide health problem. In Asian traditional medicine, Bai-Hu-Jia-Ren-Shen-Tang (BHJRST) is widely used in diabetes patients to reduce thirst. However, whether it has a therapeutic effect on T2DM or NAFLD is not known. The aim of this study was to examine whether BHJRST had a lipid-lowering effect using a HuS-E/2 cell model of fatty liver induced by palmitate and in a db/db mouse model of dyslipidemia. Incubation of HuS-E/2 cells with palmitate markedly increased lipid accumulation and expression of adipose triglyceride lipase (ATGL), which is involved in lipolysis. BHJRST significantly decreased lipid accumulation and increased ATGL levels and phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream target, acetyl-CoA carboxylase (ACC), which are involved in fatty acid oxidation. Furthermore, after twice daily oral administration for six weeks, BHJRST significantly reduced hepatic fat accumulation in db/db mice, as demonstrated by increased hepatic AMPK and ACC phosphorylation, reduced serum triglyceride levels, and reduced hepatic total lipid content. The results show that BHJRST has a lipid-lowering effect in the liver that is mediated by activation of the AMPK signaling pathway.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Kamrul M Hasan ◽  
Meher Parveen ◽  
Alondra Pena ◽  
Amiya P Sinha-Hikim ◽  
Theodore C Friedman

Abstract CARF (Collaborator of ARF), a member of ARF-MDM2-p53 pathway and an emerging multifunctional protein, regulates cellular fate in response to various stresses including oxidative DNA damage and replicative stresses. However, its role in metabolic syndrome (MS) and associated diseases has not been studied. This study, using our well established in vivo and in vitro model systems, examines the role of CARF in the development of non-alcoholic fatty liver disease (NAFLD). Indeed, we have found that, compared to control, CARF expression along with Sirt1, pAMPK and pACC (common biological markers of NAFLD) was significantly decreased in the nicotine and high-fat-diet (HFD) in combination or HFD alone induced fatty livers. Additionally, CARF expression was down regulated in palmitate (PA)-treated HepG2 cells, an in vitro model of steatosis, suggesting that CARF expression is negatively regulated in MS, such as NAFLD. Our study further revealed that shRNA mediated knockdown or lentiviral mediated over expression of CARF induced or reduced endogenous fat accumulation, respectively, in HepG2 cells. We also found that overexpression of CARF lowered the exogenous fat accumulation in PA treated HepG2 cells. RNA seq analysis after CARF knockdown in HEK-293T cells further revealed that genes associated with lipid metabolism and triglyceride (TG) synthesis such as diacylglycerol O-acyltransferase2 (DGAT2), acyl-CoA synthetase long-chain family member 4 and 6 (ACSL4, ACSL6) were upregulated in CARF-depleted cells. Likewise, we also found increased expression of DGAT2 in CARF-depleted HepG2 cells, which enhanced TG synthesis. Intriguingly, consistent with the lipid lowering effects of metformin, an antidiabetic drug, we further found that CARF expression along with pAMPK and Sirt1 were significantly increased in metformin-treated HepG2 cells. However, we also found increased pACC levels in CARF over-expressing cells which was further enhanced in metformin-treated cells, suggesting, for the first time, that CARF may contribute to lipid lowering effect of metformin by inhibiting lipogenesis. We conclude that CARF has a lipid lowering effect in hepatocytes and its down regulation in response to MS perturbs lipid metabolism that may lead to the development of NAFLD.


1976 ◽  
Vol 10 (2) ◽  
pp. 147-149 ◽  
Author(s):  
G. Schlierf ◽  
A. Stiehl ◽  
C. C. Heuck ◽  
P. D. Lang ◽  
P. Oster ◽  
...  

2010 ◽  
Vol 66 (3) ◽  
pp. 682-683 ◽  
Author(s):  
M. Fabbiani ◽  
L. Bracciale ◽  
M. Doino ◽  
L. Sidella ◽  
S. Farina ◽  
...  

PLoS ONE ◽  
2018 ◽  
Vol 13 (10) ◽  
pp. e0205430 ◽  
Author(s):  
Cristina Ruiz-Iruela ◽  
Ariadna Padró-Miquel ◽  
Xavier Pintó-Sala ◽  
Neus Baena-Díez ◽  
Assumpta Caixàs-Pedragós ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document