scholarly journals Endoplasmic Reticulum Stress Disturbs Lipid Homeostasis and Augments Inflammation in the Intestine and Isolated Intestinal Cells of Large Yellow Croaker (Larimichthys crocea)

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Fang ◽  
Qiuchi Chen ◽  
Jiamin Li ◽  
Yongtao Liu ◽  
Zengqi Zhao ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Metabolism ◽  
Er Stress ◽  
Lipid Synthesis ◽  
Whole Body ◽  
Lipid Homeostasis ◽  
Intestinal Cells ◽  
Large Yellow Croaker ◽  
Human Beings ◽  
Larimichthys Crocea

The small intestine is crucial for lipid homeostasis and immune regulation of the whole body. Endoplasmic reticulum (ER) stress may affect lipid metabolism and inflammation in the intestine, but the potential mechanism is not completely understood. In the present study, intraperitoneal injection of tunicamycin (TM) induced ER stress in the intestine of large yellow croaker (Larimichthys crocea). ER stress induced excessive accumulation of triglyceride (TG) in the intestine by promoting lipid synthesis. However, it also enhanced lipid secretion and fatty acid β-oxidation. In addition, ER stress augmented inflammation in the intestine by promoting p65 into the nucleus and increasing proinflammatory genes expression. In the isolated intestinal cells, the obtained results showed that TM treatment significantly upregulated the mRNA expression of lipid synthesis and inflammatory response genes, which were consistent with those in vivo. Moreover, overexpression of unfolded protein response (UPR) sensors significantly upregulated promoter activities of lipid synthesis and proinflammatory genes. In conclusion, the results suggested that ER stress disturbed lipid metabolism and augmented inflammation in the intestine and isolated intestinal cells of large yellow croaker, which may contribute to finding novel therapies to tackle lipid dysregulation and inflammation in the intestine of fish and human beings.

scholarly journals High Fat Activates O-GlcNAcylation and Affects AMPK/ACC Pathway to Regulate Lipid Metabolism

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1740
Author(s):  
Yuning Pang ◽  
Xiang Xu ◽  
Xiaojun Xiang ◽  
Yongnan Li ◽  
Zengqi Zhao ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Lipid Synthesis ◽  
Fat Deposition ◽  
Liver Fat ◽  
Lipid Homeostasis ◽  
High Fat ◽  
Dual Inhibitor ◽  
Regulate Lipid Metabolism

A high-fat diet often leads to excessive fat deposition and adversely affects the organism. However, the mechanism of liver fat deposition induced by high fat is still unclear. Therefore, this study aimed at acetyl-CoA carboxylase (ACC) to explore the mechanism of excessive liver deposition induced by high fat. In the present study, the ORF of ACC1 and ACC2 were cloned and characterized. Meanwhile, the mRNA and protein of ACC1 and ACC2 were increased in liver fed with a high-fat diet (HFD) or in hepatocytes incubated with oleic acid (OA). The phosphorylation of ACC was also decreased in hepatocytes incubated with OA. Moreover, AICAR dramatically improved the phosphorylation of ACC, and OA significantly inhibited the phosphorylation of the AMPK/ACC pathway. Further experiments showed that OA increased global O-GlcNAcylation and agonist of O-GlcNAcylation significantly inhibited the phosphorylation of AMPK and ACC. Importantly, the disorder of lipid metabolism caused by HFD or OA could be rescued by treating CP-640186, the dual inhibitor of ACC1 and ACC2. These observations suggested that high fat may activate O-GlcNAcylation and affect the AMPK/ACC pathway to regulate lipid synthesis, and also emphasized the importance of the role of ACC in lipid homeostasis.

scholarly journals Acute Tissue Injury Caused by Subcutaneous Fat Biopsies Produces Endoplasmic Reticulum Stress

2009 ◽  
Vol 30 (7) ◽  
pp. 928-928
Author(s):  
Guenther Boden ◽  
Matthew Silviera ◽  
Brian Smith ◽  
Peter Cheung ◽  
Carol Homko
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Tissue Injury ◽  
Subcutaneous Fat ◽  
Whole Body ◽  
Monocyte Chemoattractant Protein 1 ◽  
Homologous Protein ◽  
Stress Markers ◽  
Acute Tissue Injury ◽  
Glucose Regulated Protein

Abstract Background It is not known whether acute tissue injury is associated with endoplasmic reticulum (ER) stress. Objective Our objective was to determine whether open, sc fat biopsies cause ER stress. Approach Five healthy subjects underwent three open sc fat biopsies. The first biopsy, taken from the lateral aspect of a thigh, was followed 4 h later by a second biopsy from the same incision site and a third biopsy from the contralateral leg. Expression markers of ER stress, inflammation, hypoxia, and adipokines were measured in these fat biopsies. In addition, we tested for signs of systemic ER stress and inflammation in plasma and in circulating monocytes. Results mRNA/18s ratios of IL-6, monocyte chemoattractant protein-1, CD-14, hypoxia-induced factor 1-α, the spliced form of Xbox protein-1, glucose-regulated protein 78, CEBP homologous protein, and activating factor-4 were all severalfold higher, whereas mRNA/18s ratios of adiponectin and leptin were lower in fat biopsies taken from the same site 4 h after the first biopsy but were unchanged in the second biopsy that was taken from the contralateral site. The biopsies were not associated with changes in plasma and monocyte IL-6 concentrations or in monocyte ER stress markers. Also, whole-body insulin-stimulated glucose uptake was the same in 15 subjects who had biopsies compared with 15 different subjects who did not. Conclusion Open, sc fat biopsies produced inflammation, hypoxia, ER stress, and decreased expression of adiponectin and leptin. These changes remained confined to the biopsy site for at least 4 h.

scholarly journals Endoplasmic Reticulum Stress and Lipid Metabolism: Mechanisms and Therapeutic Potential

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Sana Basseri ◽  
Richard C. Austin
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Lipid Metabolism ◽  
Er Stress ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Signal Transduction Pathway ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Stress Dependent

The endoplasmic reticulum (ER) plays a crucial role in protein folding, assembly, and secretion. Disruption of ER homeostasis may lead to accumulation of misfolded or unfolded proteins in the ER lumen, a condition referred to as ER stress. In response to ER stress, a signal transduction pathway known as the unfolded protein response (UPR) is activated. UPR activation allows the cell to cope with an increased protein-folding demand on the ER. Recent studies have shown that ER stress/UPR activation plays a critical role in lipid metabolism and homeostasis. ER-stress-dependent dysregulation of lipid metabolism may lead to dyslipidemia, insulin resistance, cardiovascular disease, type 2 diabetes, and obesity. In this paper, we examine recent findings illustrating the important role ER stress/UPR signalling pathways play in regulation of lipid metabolism, and how they may lead to dysregulation of lipid homeostasis.

scholarly journals Exogenous acylated ghrelin promotes but un-acylated ghrelin prevents hepatic steatosis by modulating peripheral insulin resistance and hepatic oxidative and endoplasmic reticulum stress

2021 ◽  
Vol 7 (3) ◽  
Keyword(s):  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Hepatic Steatosis ◽  
Fatty Acid Synthase ◽  
Lipid Synthesis ◽  
Acylated Ghrelin ◽  
Mrna Levels ◽  
Protein Levels

Objectives: This study tested the effects of acylated (AG and un-acylated ghrelin (UAG) on hepatic lipid synthesis and insulin resistance (IR) from prospective to their effect on endoplasmic reticulum stress and investigated the possible underlying mechanisms. Methods: Healthy rats were divided as 4 groups (n=12/each) as control, control + AG, control + UAG, and control + AG + UAG (1:1). GA or UAG were given subcutaneously (200 ng/kg/each) for 8 weeks. Results: AG increased fasting levels of glucose and insulin resistance, increased hepatic glucose production, and impaired glucose and insulin tolerance. Besides, it increased serum levels of free fatty acids (FFAs), enhanced serum and hepatic levels of triglycerides and cholesterol, and increased lipid deposition in the livers of rats. Concomitantly, it stimulated the mRNA levels of SREBP1/2, fatty acid synthase, and protein levels of all arms of ER stress including Xbp-1, CHOP, ATF-6, and p-eIF2α, thus activating lipid synthesis and ER stress. It also reduced protein levels of p-IRS (Tyr612), p-Akt (Ser307), and increased levels of ROS, TNF-α, IL-6, and protein levels of cleaved caspase-12, p-IRS (Ser307), and p-JNK (The183/Tyr186) in rats’ livers. Administration of UAG alone or in combination with AG produced contradictory effects. However, both AG and UAG significantly increased mRNA levels of AMPK and PPARα suggesting FAs oxidation. Conclusion: AG induces hepatic steatosis and suppresses hepatic insulin signaling mainly by inducing peripheral IR that is associated with hepatic oxidative stress, inflammation, and ER stress. However, UAG alone or in combination exerts opposite effects.

scholarly journals Angiotensin-converting enzyme 2 regulates endoplasmic reticulum stress and mitochondrial function to preserve skeletal muscle lipid metabolism

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Xi Cao ◽  
Xin-Meng Lu ◽  
Xiu Tuo ◽  
Jing-Yi Liu ◽  
Yi-Chen Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endoplasmic Reticulum ◽  
Lipid Metabolism ◽  
Er Stress ◽  
Mitochondrial Function ◽  
Knockout Mice ◽  
Intramuscular Fat ◽  
Muscle Lipid ◽  
Angiotensin Converting Enzyme 2 ◽  
Skeletal Muscle Lipid

Abstract Objective Endoplasmic reticulum (ER) stress and mitochondrial function affected intramuscular fat accumulation. However, there is no clear evident on the effect of the regulation of ER stress and mitochondrial function by Angiotensin-converting enzyme 2 (ACE2) on the prevention of intramuscular fat metabolism. We investigated the effects of ACE2 on ER stress and mitochondrial function in skeletal muscle lipid metabolism. Methods The triglyceride (TG) content in skeletal muscle of ACE2 knockout mice and Ad-ACE2-treated db/db mice were detected by assay kits. Meanwhile, the expression of lipogenic genes (ACCα, SREBP-1c, LXRα, CPT-1α, PGC-1α and PPARα), ER stress and mitochondrial function related genes (GRP78, eIF2α, ATF4, BCL-2, and SDH6) were analyzed by RT-PCR. Lipid metabolism, ER stress and mitochondrial function related genes were analyzed by RT-PCR in ACE2-overexpression C2C12 cell. Moreover, the IKKβ/NFκB/IRS-1 pathway was determined using lysate sample from skeletal muscle of ACE2 knockout mice. Results ACE2 deficiency in vivo is associated with increased lipid accumulation in skeletal muscle. The ACE2 knockout mice displayed an elevated level of ER stress and mitochondrial dysfunctions in skeletal muscle. In contrast, activation of ACE2 can ameliorate ER stress and mitochondrial function, which slightly accompanied by reduced TG content and down-regulated the expression of skeletal muscle lipogenic proteins in the db/db mice. Additionally, ACE2 improved skeletal muscle lipid metabolism and ER stress genes in the C2C12 cells. Mechanistically, endogenous ACE2 improved lipid metabolism through the IKKβ/NFκB/IRS-1 pathway in skeletal muscle. Conclusions ACE2 was first reported to play a notable role on intramuscular fat regulation by improving endoplasmic reticulum and mitochondrial function. This study may provide a strategy for treating insulin resistance in skeletal muscle.

scholarly journals PPARs as Metabolic Regulators in the Liver: Lessons from Liver-Specific PPAR-Null Mice

2020 ◽  
Vol 21 (6) ◽  
pp. 2061 ◽  
Author(s):  
Yaping Wang ◽  
Takero Nakajima ◽  
Frank J. Gonzalez ◽  
Naoki Tanaka
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Liver Cancer ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Lipid Homeostasis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Metabolic Regulators

Peroxisome proliferator-activated receptor (PPAR) α, β/δ, and γ modulate lipid homeostasis. PPARα regulates lipid metabolism in the liver, the organ that largely controls whole-body nutrient/energy homeostasis, and its abnormalities may lead to hepatic steatosis, steatohepatitis, steatofibrosis, and liver cancer. PPARβ/δ promotes fatty acid β-oxidation largely in extrahepatic organs, and PPARγ stores triacylglycerol in adipocytes. Investigations using liver-specific PPAR-disrupted mice have revealed major but distinct contributions of the three PPARs in the liver. This review summarizes the findings of liver-specific PPAR-null mice and discusses the role of PPARs in the liver.

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