Inflammation and Adipose Dysfunction

2010 ◽  
pp. 155-173
Author(s):  
Rachana Shah ◽  
Muredach P. Reilly
Keyword(s):  
Adipose Dysfunction

Elafibranor interrupts adipose dysfunction-mediated gut and liver injury in mice with alcoholic steatohepatitis

2019 ◽  
Vol 133 (3) ◽  
pp. 531-544 ◽  
Author(s):  
Tzu-Hao Li ◽  
Ying-Ying Yang ◽  
Chia-Chang Huang ◽  
Chih-Wei Liu ◽  
Hung-Cheng Tsai ◽  
...  
Keyword(s):  
Liver Injury ◽  
Energy Homeostasis ◽  
Intestinal Barrier ◽  
Peroxisome Proliferator ◽  
Intestinal Epithelial ◽  
Peroxisome Proliferator Activated Receptor ◽  
Alcoholic Steatohepatitis ◽  
Ppar Agonists ◽  
Apoptosis And Inflammation ◽  
Adipose Dysfunction

Abstract Background: Reversal of alcohol-induced peroxisome proliferator-activated receptor (PPAR) α (PPARα) and PPARδ dysfunction has been reported to decrease the severity of alcoholic steatohepatitis (ASH). Autophagy is essential for cell survival and tissue energy homeostasis. Emerging evidence indicates that alcohol-induced adipose tissue (AT) autophagy dysfunction contributes to injury in the intestine, liver, and AT of ASH. Methods: The effects and mechanisms of dual PPARα/δ agonist elafibranor on autophagy stimulation were investigated using mice with ASH. Results: C57BL/6 mice on ethanol diet showed AT dysfunction, disrupted intestinal barrier, and ASH, which was accompanied by alcohol-mediated decrease in PPARα, PPARδ, and autophagy levels in intestine, liver, and AT. Chronic treatment with elafibranor attenuated AT apoptosis and inflammation by restoration of tissue PPARα, PPARδ, and autophagy levels. In ASH mice, alcohol-induced AT dysfunction along with increased fatty acid (FA) uptake and decreased free FA (FFA) release from AT was inhibited by elafibranor. The improvement of AT autophagy dysfunction by elafibranor alleviated inflammation and apoptosis-mediated intestinal epithelial disruption in ASH mice. Acute elafibranor incubation inhibited ethanol-induced ASH-mice-sera-enhanced autophagy dysfunction, apoptosis, barrier disruption, and intracellular steatosis in Caco-2 cells and primary hepatocytes (PHs). Conclusion: Altogether, these findings demonstrated that the PPARα/δ agonist, elafibranor, decreased the severity of liver injury by restoration of alcohol-suppressed AT autophagy function and by decreasing the release of apoptotic markers, inflammatory cytokines, and FFA, thereby reducing intestinal epithelium disruption and liver inflammation/apoptosis/steatosis in ASH mice. These data suggest that dual PPAR agonists can serve as potential therapeutic agents for the management of ASH.

scholarly journals Surgical fat removal exacerbates metabolic disorders but not atherogenesis in LDLR−/− mice fed on high-fat diet

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lin Liu ◽  
Chenxi Liang ◽  
Xiaowei Wang ◽  
Xiayu Ding ◽  
Yingjing Lu ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Metabolic Disorders ◽  
Subcutaneous Fat ◽  
Surgical Removal ◽  
High Fat ◽  
Fat Depots ◽  
Systemic Insulin Resistance ◽  
Significant Difference ◽  
Fat Removal ◽  
Adipose Dysfunction

AbstractLipodystrophy is a severe adipose dysfunction that can be classified as congenital or acquired lipodystrophy, in term of the etiology. Previous knowledge about the metabolic disorders and cardiovascular consequences were mostly obtained from lipodystrophic mice with genetic defects. To completely rule out the genetic influence, we established a mouse model of acquired generalized lipodystrophy by surgical removal of multiple fat depots, including subcutaneous fat in the inguinal, visceral fat in the epididymis and brown fat in the scapula, in atherosclerosis-prone LDLR−/− mice which were fed with a high-fat diet (HFD). It was observed that fat removal increased diet-induced hyperlipidemia, especially hypercholesteremia, as early as 2 weeks after HFD and till the end of HFD feeding. After 12 weeks on the HFD, the residual fats of fat-removed mice were found expanded. Although fat removal aggravated diet-induced lipid deposition in the liver and systemic insulin resistance, there was no significant difference in atherogenesis in fat-removed mice compared with sham-operated control mice. Acquired generalized lipodystrophy by surgical fat removal promoted metabolic disorders but not atherogenesis in LDLR−/− mice fed on HFD.

scholarly journals Metabolic endotoxemia promotes adipose dysfunction and inflammation in human obesity

2019 ◽  
Vol 316 (2) ◽  
pp. E319-E332 ◽  
Author(s):  
Mercedes Clemente-Postigo ◽  
Wilfredo Oliva-Olivera ◽  
Leticia Coin-Aragüez ◽  
Bruno Ramos-Molina ◽  
Rosa María Giraldez-Perez ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
In Vitro Assays ◽  
Low Grade ◽  
Human Obesity ◽  
Gene And Protein Expression ◽  
And Function ◽  
Adipose Dysfunction ◽  
High Degree ◽  
Metabolic Endotoxemia

Impaired adipose tissue (AT) lipid handling and inflammation is associated with obesity-related metabolic diseases. Circulating lipopolysaccharides (LPSs) from gut microbiota (metabolic endotoxemia), proposed as a triggering factor for the low-grade inflammation in obesity, might also be responsible for AT dysfunction. Nevertheless, this hypothesis has not been explored in human obesity. To analyze the relationship between metabolic endotoxemia and AT markers for lipogenesis, lipid handling, and inflammation in human obesity, 33 patients with obesity scheduled for surgery were recruited and classified according to their LPS levels. Visceral and subcutaneous AT gene and protein expression were analyzed and adipocyte and AT in vitro assays performed. Subjects with obesity with a high degree of metabolic endotoxemia had lower expression of key genes for AT function and lipogenesis ( SREBP1, FABP4, FASN, and LEP) but higher expression of inflammatory genes in visceral and subcutaneous AT than subjects with low LPS levels. In vitro experiments corroborated that LPS are responsible for adipocyte and AT inflammation and downregulation of PPARG, SCD, FABP4, and LEP expression and LEP secretion. Thus, metabolic endotoxemia influences AT physiology in human obesity by decreasing the expression of factors involved in AT lipid handling and function as well as by increasing inflammation.

scholarly journals Maternal Docosahexaenoic Acid Increases Adiponectin and Normalizes IUGR-Induced Changes in Rat Adipose Deposition

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Heidi N. Bagley ◽  
Yan Wang ◽  
Michael S. Campbell ◽  
Xing Yu ◽  
Robert H. Lane ◽  
...  
Keyword(s):  
Docosahexaenoic Acid ◽  
Receptor Expression ◽  
Male Rats ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pregnancy And Lactation ◽  
Maternal Supplementation ◽  
Induced Changes ◽  
Adipose Dysfunction ◽  
Visceral Adipose

Intrauterine growth restriction (IUGR) predisposes to obesity and adipose dysfunction. We previously demonstrated IUGR-induced increased visceral adipose deposition and dysregulated expression of peroxisome proliferator activated receptor-γ2 (PPARγ2) in male adolescent rats, prior to the onset of obesity. In other studies, activation of PPARγincreases subcutaneous adiponectin expression and normalizes visceral adipose deposition. We hypothesized that maternal supplementation with docosahexaenoic acid (DHA), a PPARγagonist, would normalize IUGR adipose deposition in association with increased PPARγ, adiponectin, and adiponectin receptor expression in subcutaneous adipose. To test these hypotheses, we used a well-characterized model of uteroplacental-insufficiency-(UPI-) induced IUGR in the rat with maternal DHA supplementation. Our primary findings were that maternal DHA supplementation during rat pregnancy and lactation (1) normalizes IUGR-induced changes in adipose deposition and visceral PPARγexpression in male rats and (2) increases serum adiponectin, as well as adipose expression of adiponectin and adiponectin receptors in former IUGR rats. Our novel findings suggest that maternal DHA supplementation may normalize adipose dysfunction and promote adiponectin-induced improvements in metabolic function in IUGR.

Growth Hormone Ameliorates Adipose Dysfunction During Oxidative Stress and Inflammation and Improves Glucose Tolerance in Obese Mice

2014 ◽  
Vol 46 (09) ◽  
pp. 656-662 ◽  
Author(s):  
M. Fukushima ◽  
Y. Okamoto ◽  
H. Katsumata ◽  
M. Ishikawa ◽  
S. Ishii ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Hormone ◽  
Glucose Tolerance ◽  
Obese Mice ◽  
Adipose Dysfunction

scholarly journals A indicator of visceral adipose dysfunction to evaluate metabolic health in adult Chinese

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Ming-Feng Xia ◽  
Ying Chen ◽  
Huan-Dong Lin ◽  
Hui Ma ◽  
Xiao-Ming Li ◽  
...  
Keyword(s):  
Metabolic Health ◽  
Adipose Dysfunction ◽  
Visceral Adipose

scholarly journals Recent Advances in Adipose Tissue Dysfunction and Its Role in the Pathogenesis of Non-Alcoholic Fatty Liver Disease

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3300
Author(s):  
Xiaoxiao Wang ◽  
Huiying Rao ◽  
Feng Liu ◽  
Lai Wei ◽  
Honggui Li ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Current Knowledge ◽  
Low Grade ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Adipose Tissue Dysfunction ◽  
Adipose Dysfunction

Obesity is a serious ongoing health problem that significantly increases the incidence of nonalcoholic fatty liver disease (NAFLD). During obesity, adipose tissue dysfunction is obvious and characterized by increased fat deposition (adiposity) and chronic low-grade inflammation. The latter has been implicated to critically promote the development and progression of NAFLD, whose advanced form non-alcoholic steatohepatitis (NASH) is considered one of the most common causes of terminal liver diseases. This review summarizes the current knowledge on obesity-related adipose dysfunction and its roles in the pathogenesis of hepatic steatosis and inflammation, as well as liver fibrosis. A better understanding of the crosstalk between adipose tissue and liver under obesity is essential for the development of new and improved preventive and/or therapeutic approaches for managing NAFLD.

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