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Specialty: Physiology
Condition: Liver Disease

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Total 16 results found since Jan 2013.

ATF4-mediated CD36 Upregulation Contributes to Palmitate-induced Lipotoxicity in Hepatocytes
In this study, our data revealed for the first time that ATF4 plays a critical role in mediating hepatic CD36 expression. Genetic inhibition of ATF4 attenuated CD36 upregulation induced by either palmitate or ER stress inducer tunicamycin in hepatocytes. In mice, tunicamycin upregulates liver CD36 expression, whereas hepatocyte-specific ATF4 knockout mice manifest lower hepatic CD36 expression when compared to control animals. Furthermore, we demonstrated that CD36 upregulation upon palmitate exposure represents a feedforward mechanism in that siRNA knockdown of CD36 in hepatocytes blunted ATF4 activation induced by both p...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - February 28, 2023 Category: Physiology Authors: Alexandra Griffiths Jun Wang Qing Song Samuel Man Lee Jose Cordoba-Chacon Zhenyuan Song Source Type: research

RNA-Seq Reveals Different Gene Expression in Liver-Specific Prohibitin 1 Knock-Out Mice
In this study, we performed RNA-sequencing (RNA-seq) analysis with liver tissues to investigate global gene expression among liver-specific Phb1−/−, Phb1+/−, and WT mice, focusing on the differentially expressed (DE) genes between Phb1+/− and WT. When 78 DE genes were analyzed for biological functions, using ingenuity pathway analysis (IPA) tool, lipid metabolism-related genes, including insulin receptor (Insr), sterol regulatory element-binding transcription factor 1 (Srebf1), Srebf2, and SREBP cleavage-activating protein (Scap) appeared to be downregulated in liver-specific Phb1+/− compared with WT. Diseases an...
Source: Frontiers in Physiology - September 3, 2021 Category: Physiology Source Type: research

GPR40-Deficiency Is Associated with Hepatic FAT/CD36 Upregulation, Steatosis, Inflammation and Cell Injury in C57BL/6 Mice.
In this study, we fed wild-type or GPR40 knockout C57BL/6 mice high-fat diet (HFD) for 20 weeks and then assessed the effect of GPR40-deficiency on HFD-induced NAFLD. Assays on metabolic parameters showed that HFD increased bodyweight, glucose, insulin, insulin resistance, cholesterol and alanine aminotransferase (ALT), and GPR40-deficiency did not mitigate the HFD-induced metabolic abnormalities. In contrast, we found that GPR40-deficiency was associated with increased bodyweight, insulin, insulin resistance, cholesterol and ALT in control mice fed low fat diet (LFD). Surprisingly, histology and Oil Red O staining showed ...
Source: American Journal of Physiology. Endocrinology and Metabolism - October 26, 2020 Category: Physiology Authors: Lu Z, Li Y, Syn WK, Li AJ, Ritter S, Wank SA, Lopes-Virella MF, Huang Y Tags: Am J Physiol Endocrinol Metab Source Type: research

Hypoxia exacerbates non-alcoholic fatty liver disease via HIF-2 α/PPARα pathway.
This study aimed to investigate whether hypoxia can affect non-alcoholic fatty liver disease (NAFLD) progression and the associated mechanisms, specifically regarding the HIF-2α / PPARα pathway in vitro and vivo. Recent studies have reported that, compared with HIF-1α, HIF-2α has different effects on lipid metabolism. We propose hypoxia may exacerbate NAFLD by the HIF-2α upregulation-induced suppression of PPARα in the liver. To verify this hypothesis, a steatotic human hepatocyte (L02) cell line treated with free fatty acids and a mouse model of NAFLD fed a high-fat diet were used. Steatotic hepatocytes were treated...
Source: American Journal of Physiology. Endocrinology and Metabolism - August 19, 2019 Category: Physiology Authors: Chen J, Chen J, Fu H, Li Y, Wang L, Luo S, Lu H Tags: Am J Physiol Endocrinol Metab Source Type: research

Resveratrol protects against nonalcoholic fatty liver disease by improving lipid metabolism and redox homeostasis via the PPAR α pathway
This study investigated the preventive and therapeutic effects of RSV on high-fat diet (HFD)-induced NAFLD in rats and palmitate acid (PA)-induced hepatocyte steatosis in HepG2 cells. Hepatocytes were incubated with inhibitors of peroxisome proliferator-activated receptor α (PPARα) or short interfering RNAs (siRNAs) targeting PPARα, AMP-activated protein kinase (AMPK), and protein kinase A (PKA) to determine the underlying mechanisms. We found that RSV noticeably ameliorated HFD-induced hepatic steatosis in rats and inhibited PA-induced lipid accumulation in HepG2 cells. Moreover, RSV improved lipid metabolism, enhanced...
Source: Applied Physiology, Nutrition, and Metabolism - June 6, 2019 Category: Physiology Authors: Yujie Huang Hedong Lang Ka Chen Yong Zhang Yanxiang Gao Li Ran Long Yi Mantian Mi Qianyong Zhang Source Type: research

Tangshen Formula Alleviates Hepatic Steatosis by Inducing Autophagy Through the AMPK/SIRT1 Pathway
Conclusion In conclusion, the present study demonstrated that autophagy was involved in relieving the effects of TSF against NAFLD, which were mediated by the AMPK/SIRT1 pathway (Figure 7D). These findings may improve our current understanding of the role of TSF in treating hepatic steatosis and provide an experimental basis for the clinical application of TSF in NAFLD and its related metabolic syndrome. Ethics Statement This study was carried out in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Ethics Co...
Source: Frontiers in Physiology - April 25, 2019 Category: Physiology Source Type: research

Increasing Upstream Chromatin Long –Range Interactions May Favor Induction of Circular RNAs in LysoPC-Activated Human Aortic Endothelial Cells
We examined the sponging potential of all significantly changed circRNAs using the CircInteractome database (Montefiori et al., 2018), recording two miRNAs with four or more predicted binding sites in a single circRNA transcript, a threshold above which meaningful sponging activity is likely to occur Memczak et al. (2013). Another four significantly changed circRNAs are experimentally shown to sponge miRNAs (Dudekula et al., 2016; Chen et al., 2017; Yan et al., 2017; Wang et al., 2018), for six total circRNAs with miRNA sponging activity including miR125, miR143, miR1272, miR153, miR515-5p, and miR196a-5p (Table 4). In Fig...
Source: Frontiers in Physiology - April 17, 2019 Category: Physiology Source Type: research

FGF21 as Modulator of Metabolism in Health and Disease
In conclusion, FGF21 belongs to a promising class of cytokines that are induced in response to stress and that can be used as a drug, drug target, or through a biomarker, depending on the physio-pathological context. All these findings will become clear when FGF21 will be used as a therapeutic molecule, exploiting the beneficial effects of FGF21 for treating metabolic disease or when it will be blocked to ameliorate disease progression and the onset of disease. Author Contributions CT and MS wrote the manuscript. VR contributed to the discussion. Funding This work was supported from the AFM-Telethon (19524), Italian Mi...
Source: Frontiers in Physiology - April 16, 2019 Category: Physiology Source Type: research

Heat Shock Protein 72 Regulates Hepatic Lipid Accumulation.
Abstract Induction of the chaperone Heat Shock Protein 72 (HSP72) through heat treatment, exercise, or overexpression improves glucose tolerance and mitochondrial function in skeletal muscle. Less is known about HSP72 function in the liver where lipid accumulation can result in insulin resistance and Nonalcoholic Fatty Liver Disease (NAFLD). The purpose of this study was 1) to determine whether weekly in vivo heat treatment (HT) induces hepatic HSP72 and improves glucose tolerance in rats fed a high-fat diet (HFD) and 2) to determine the ability of HSP72 to protect against lipid accumulation and mitochondrial dysf...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - June 20, 2018 Category: Physiology Authors: Archer AE, Rogers RS, Von Schulze AT, Wheatley JL, Morris EM, McCoin CS, Thyfault JP, Geiger PC Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research

Metabolic profiling reveals that pnpla3 induces widespread effects on metabolism beyond triacylglycerol remodeling in huh-7 hepatoma cells.
METABOLIC PROFILING REVEALS THAT PNPLA3 INDUCES WIDESPREAD EFFECTS ON METABOLISM BEYOND TRIACYLGLYCEROL REMODELING IN HUH-7 HEPATOMA CELLS. Am J Physiol Gastrointest Liver Physiol. 2014 Apr 24; Authors: Min HK, Sookoian SC, Pirola CJ, Cheng J, Mirshahi F, Sanyal AJ Abstract PNPLA3 was recently associated with the susceptibility to nonalcoholic fatty liver disease, a common cause of chronic liver disease characterized by abnormal triglyceride accumulation. While it is established that PNPLA3 has both triacylglycerol lipase and acylglycerol O-acyltransferase activities, is still unknown whether the gene...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - April 24, 2014 Category: Physiology Authors: Min HK, Sookoian SC, Pirola CJ, Cheng J, Mirshahi F, Sanyal AJ Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research