Berteroin ameliorates lipid accumulation through AMPK-mediated regulation of hepatic lipid metabolism and inhibition of adipocyte differentiation

Life Sciences ◽  
2021 ◽  
pp. 119668
Author(s):  
Yeon Ju Kim ◽  
Sung Yun Park ◽  
Ju-Hee Lee
Keyword(s):  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
Adipocyte Differentiation ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid

scholarly journals Hepatic MIR20B promotes nonalcoholic fatty liver disease by suppressing PPARA

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Yo Han Lee ◽  
Hyun-Jun Jang ◽  
Sounkou Kim ◽  
Sun Sil Choi ◽  
Keon Woo Khim ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Network Analysis ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Synergic Effect ◽  
Hepatic Lipid Metabolism ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid

Background:Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and imbalances in lipid metabolism in the liver. Although nuclear receptors (NRs) play a crucial role in hepatic lipid metabolism, the underlying mechanisms of NR regulation in NAFLD remain largely unclear. Methods:Using network analysis and RNA-seq to determine the correlation between NRs and microRNA in human NAFLD patients, we revealed that MIR20B specifically targets PPARA. MIR20B mimic and anti-MIR20B were administered to human HepG2 and Huh-7 cells and mouse primary hepatocytes as well as high fat diet (HFD)- or methionine-deficient diet (MCD)-fed mice to verify the specific function of MIR20B in NAFLD. We tested the inhibition of the therapeutic effect of a PPARα agonist, fenofibrate, by Mir20b and the synergic effect of combination of fenofibrate with anti-Mir20b in NAFLD mouse model. Results:We revealed that MIR20B specifically targets PPARA through miRNA regulatory network analysis of nuclear receptor genes in NAFLD. The expression of MIR20B was upregulated in free fatty acid (FA)-treated hepatocytes and the livers of both obesity-induced mice and NAFLD patients. Overexpression of MIR20B significantly increased hepatic lipid accumulation and triglyceride levels. Furthermore, MIR20B significantly reduced FA oxidation and mitochondrial biogenesis by targeting PPARA. In Mir20b-introduced mice, the effect of fenofibrate to ameliorate hepatic steatosis was significantly suppressed. Finally, inhibition of Mir20b significantly increased FA oxidation and uptake, resulting in improved insulin sensitivity and a decrease in NAFLD progression. Moreover, combination of fenofibrate and anti-Mir20b exhibited the synergic effect on improvement of NAFLD in MCD-fed mice. Conclusions:Taken together, our results demonstrate that the novel MIR20B targets PPARA, plays a significant role in hepatic lipid metabolism, and present an opportunity for the development of novel therapeutics for NAFLD. Funding:This research was funded by Korea Mouse Phenotyping Project (2016M3A9D5A01952411), the National Research Foundation of Korea (NRF) grant funded by the Korea government (2020R1F1A1061267, 2018R1A5A1024340, NRF-2021R1I1A2041463, 2020R1I1A1A01074940), and the Future-leading Project Research Fund (1.210034.01) of UNIST.

scholarly journals Perturbation of TM6SF2 Expression Alters Lipid Metabolism in a Human Liver Cell Line

2021 ◽  
Vol 22 (18) ◽  
pp. 9758
Author(s):  
Asmita Pant ◽  
Yue Chen ◽  
Annapurna Kuppa ◽  
Xiaomeng Du ◽  
Brian D. Halligan ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
Fluorescent Imaging ◽  
Genome Wide Association Studies ◽  
Loss Of Function ◽  
Wild Type ◽  
Hepatic Lipid Metabolism ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Human Liver Cell

Non-alcoholic fatty liver disease (NAFLD) is caused by excess lipid accumulation in hepatocytes. Genome-wide association studies have identified a strong association of NAFLD with non-synonymous E167K amino acid mutation in the transmembrane 6 superfamily member 2 (TM6SF2) protein. The E167K mutation reduces TM6SF2 stability, and its carriers display increased hepatic lipids and lower serum triglycerides. However, the effects of TM6SF2 on hepatic lipid metabolism are not completely understood. We overexpressed wild-type or E167K variant of TM6SF2 or knocked down TM6SF2 expression in lipid-treated Huh-7 cells and used untargeted lipidomic analysis, RNAseq transcriptome analysis, and fluorescent imaging to determine changes in hepatic lipid metabolism. Both TM6SF2 knockdown and E167K overexpression increased hepatic lipid accumulation, while wild-type overexpression decreased acylglyceride levels. We also observed lipid chain remodeling for acylglycerides by TM6SF2 knockdown, leading to a relative increase in species with shorter, more saturated side chains. RNA-sequencing revealed differential expression of several lipid metabolizing genes, including genes belonging to AKR1 family and lipases, primarily in cells with TM6SF2 knockdown. Taken together, our data show that overexpression of TM6SF2 gene or its loss-of-function changes hepatic lipid species composition and expression of lipid metabolizing genes. Additionally, our data further confirms a loss-of-function effect for the E167K variant.

Altered hepatic lipid metabolism in leptin-deficlent mice

2001 ◽  
Vol 120 (5) ◽  
pp. A546-A546
Author(s):  
D SWARTZBASILE ◽  
M GOLDBLATT ◽  
C SVATEK ◽  
M WALTERS ◽  
S CHOI ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid

Prenatal programming of hepatic lipid metabolism: Sex, hormones and lifelong health

2020 ◽  
Author(s):  
Katarzyna Siemienowicz ◽  
Panagiotis Filis ◽  
Chiara Talia ◽  
Jennifer Thomas ◽  
Paul Fowler ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Sex Hormones ◽  
Prenatal Programming ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid
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