Dietary sweet cherry anthocyanins attenuates diet-induced hepatic steatosis by improving hepatic lipid metabolism in mice

Nutrition ◽  
2016 ◽  
Vol 32 (7-8) ◽  
pp. 827-833 ◽  
Author(s):  
Haizhao Song ◽  
Tao Wu ◽  
Dongdong Xu ◽  
Qiang Chu ◽  
Dingbo Lin ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
Sweet Cherry ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid

scholarly journals Glucagon-induced extracellular cAMP regulates hepatic lipid metabolism

2017 ◽  
Vol 234 (2) ◽  
pp. 73-87 ◽  
Author(s):  
Sihan Lv ◽  
Xinchen Qiu ◽  
Jian Li ◽  
Jinye Liang ◽  
Weida Li ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
Fatty Acid Oxidation ◽  
Lipid Homeostasis ◽  
Acid Oxidation ◽  
Intracellular Camp ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Extracellular Camp

Hormonal signals help to maintain glucose and lipid homeostasis in the liver during the periods of fasting. Glucagon, a pancreas-derived hormone induced by fasting, promotes gluconeogenesis through induction of intracellular cAMP production. Glucagon also stimulates hepatic fatty acid oxidation but the underlying mechanism is poorly characterized. Here we report that following the acute induction of gluconeogenic genes Glucose 6 phosphatase (G6Pase) and Phosphoenolpyruvate carboxykinase (Pepck) expression through cAMP-response element-binding protein (CREB), glucagon triggers a second delayed phase of fatty acid oxidation genes Acyl-coenzyme A oxidase (Aox) and Carnitine palmitoyltransferase 1a (Cpt1a) expression via extracellular cAMP. Increase in extracellular cAMP promotes PPARα activity through direct phosphorylation by AMP-activated protein kinase (AMPK), while inhibition of cAMP efflux greatly attenuates Aox and Cpt1a expression. Importantly, cAMP injection improves lipid homeostasis in fasted mice and obese mice, while inhibition of cAMP efflux deteriorates hepatic steatosis in fasted mice. Collectively, our results demonstrate the vital role of glucagon-stimulated extracellular cAMP in the regulation of hepatic lipid metabolism through AMPK-mediated PPARα activation. Therefore, strategies to improve cAMP efflux could serve as potential new tools to prevent obesity-associated hepatic steatosis.

scholarly journals Influence of Genistein on Hepatic Lipid Metabolism in an In Vitro Model of Hepatic Steatosis

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1156
Author(s):  
Lena Seidemann ◽  
Anne Krüger ◽  
Victoria Kegel-Hübner ◽  
Daniel Seehofer ◽  
Georg Damm
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Protein Expression ◽  
Hepatic Steatosis ◽  
In Vitro Model ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Genistein Treatment ◽  
Vitro Model

Nonalcoholic fatty liver disease (NAFLD) is among the leading causes of end-stage liver disease. The impaired hepatic lipid metabolism in NAFLD is exhibited by dysregulated PPARα and SREBP-1c signaling pathways, which are central transcription factors associated with lipid degradation and de novo lipogenesis. Despite the growing prevalence of this disease, current pharmacological treatment options are unsatisfactory. Genistein, a soy isoflavone, has beneficial effects on lipid metabolism and may be a candidate for NAFLD treatment. In an in vitro model of hepatic steatosis, primary human hepatocytes (PHHs) were incubated with free fatty acids (FFAs) and different doses of genistein. Lipid accumulation and the cytotoxic effects of FFAs and genistein treatment were evaluated by colorimetric and enzymatic assays. Changes in lipid homeostasis were examined by RT-qPCR and Western blot analyses. PPARα protein expression was induced in steatotic PHHs, accompanied by an increase in CPT1L and ACSL1 mRNA. Genistein treatment increased PPARα protein expression only in control PHHs, while CPTL1 and ACSL1 were unchanged and PPARα mRNA was reduced. In steatotic PHHs, genistein reversed the increase in activated SREBP-1c protein. The model realistically reflected the molecular changes in hepatic steatosis. Genistein suppressed the activation of SREBP-1c in steatotic hepatocytes, but the genistein-mediated effects on PPARα were abolished by high hepatic lipid levels.

scholarly journals Alcohol effects on hepatic lipid metabolism

2020 ◽  
Vol 61 (4) ◽  
pp. 470-479 ◽  
Author(s):  
Sookyoung Jeon ◽  
Rotonya Carr
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Hepatic Steatosis ◽  
De Novo ◽  
Lipid Synthesis ◽  
Acid Oxidation ◽  
Lipid Uptake ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease with significant morbidity and mortality worldwide. ALD begins with simple hepatic steatosis and progresses to alcoholic steatohepatitis, fibrosis, and cirrhosis. The severity of hepatic steatosis is highly associated with the development of later stages of ALD. This review explores the disturbances of alcohol-induced hepatic lipid metabolism through altered hepatic lipid uptake, de novo lipid synthesis, fatty acid oxidation, hepatic lipid export, and lipid droplet formation and catabolism. In addition, we review emerging data on the contributions of genetics and bioactive lipid metabolism in alcohol-induced hepatic lipid accumulation.

scholarly journals CARF (CDKN2AIP) Regulates Hepatic Lipid Metabolism and Protects Against Development of Non-Alcoholic Fatty Liver Diseases

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A284-A284
Author(s):  
Kamrul M Hasan ◽  
Meher Parveen ◽  
Alondra Pena ◽  
Erick Galdamez Calles ◽  
Marvy Gergis ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Mouse Model ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Hepg2 Cells ◽  
Liver Diseases ◽  
Hepatic Lipid Metabolism ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid

Abstract Non-alcoholic fatty liver diseases (NAFLD) is the most common form of liver diseases in the USA with 30–40% of American being affected and about 12% with nonalcoholic steatohepatitis (NASH), a leading cause of end-stage liver diseases. NAFLD has been linked with insulin resistance, type2 diabetes, obesity, and cardiovascular diseases but molecular mechanisms underlying the development of NAFLD and its association with metabolic syndromes are poorly understood. In this study, we explored the role of CARF (collaborator of ARF) also known as CDKN2AIP, a novel gene of ARF-MDM2-p53 pathway in the development of NAFLD. It has been shown that, p53, beyond its tumor suppressor functions, can regulate the cellular glucose and lipid metabolism and its activation has been reported to induce hepatic steatosis in mice. However, as a regulator of p53 pathway, the role of CARF in the lipid metabolism and associated metabolic diseases has not been studied yet. Using high-fat diet (HFD) fed obesity mouse model of NAFLD we found that the expression of CARF along with Sirt1, pAMPK, and pACC was significantly decreased in the HFD induced fatty livers compared to control. Similarly, CARF expression was also down-regulated in palmitate (PA)-treated HepG2 cells, an in vitro model of steatosis. We also observed that shRNA mediated knockdown or lentiviral vector mediated overexpression of CARF induced or reduced the endogenous fat accumulation, respectively, in HepG2 cells, suggesting that CARF expression is negatively regulated in NAFLD. Additionally, we performed RNA seq analysis after CARF silencing in HepG2 cells and demonstrated that silencing of CARF altered the expression of genes regulating hepatic de novo lipogenesis, beta-oxidation, and lipid secretion all of which favor the accumulation of fat in the hepatocytes. Furthermore, genes associated with mitochondrial functions such as the TCA cycle and oxidative phosphorylation were also altered which could play a role in the development of NAFLD. Finally, we demonstrated that AAV mediated hepatic overexpression of CARF in HFD fed mouse model significantly reduced the fat accumulation in the liver as evident by H&E staining of liver sections and intrahepatic triglyceride level. Altogether we conclude that CARF plays a vital role in hepatic lipid metabolism and its downregulation perturbs lipid homeostasis leading to hepatic steatosis and the development of NAFLD.

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
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