Increased Gut Permeability and Microbiota Change Associate with Mesenteric Fat Infl ammation and Metabolic Dysfunction in Diet-Induced Obese Mice

2014 ◽  
pp. 77-102
Keyword(s):  
Metabolic Dysfunction ◽  
Obese Mice ◽  
Gut Permeability ◽  
Mesenteric Fat

scholarly journals Increased Gut Permeability and Microbiota Change Associate with Mesenteric Fat Inflammation and Metabolic Dysfunction in Diet-Induced Obese Mice

PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e34233 ◽  
Author(s):  
Yan Y. Lam ◽  
Connie W. Y. Ha ◽  
Craig R. Campbell ◽  
Andrew J. Mitchell ◽  
Anuwat Dinudom ◽  
...  
Keyword(s):  
Metabolic Dysfunction ◽  
Obese Mice ◽  
Gut Permeability ◽  
Mesenteric Fat

Abstract 3203: The role of Neprilysin in the Development of Insulin Resistance, Type 2 Diabetes and Cardiovascular Disease

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kristina F Standeven ◽  
Angela M Carter ◽  
Anthony J Balmforth ◽  
Stephen B Wheatcroft ◽  
Nigel M Hooper ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Vascular Function ◽  
Animal Studies ◽  
Obese Mice ◽  
Human Adipocytes ◽  
The Metabolic Syndrome ◽  
Mesenteric Fat ◽  
Order Of Magnitude ◽  
Average Gene

Neprilysin (NEP) cleaves several bioactive peptides involved in the regulation of vascular function. In human microvascular endothelial cells, fatty acids and glucose increase NEP activity, and inhibition of NEP in animal studies results in increased insulin sensitivity, suggesting that NEP may be related to the metabolic syndrome. We tested this hypothesis in cell, animal and human based models. Microarray analysis of mRNA expression in differentiated human adipocytes (Affymetrix Human Genome U133 Plus 2.0 arrays) showed NEP expression to be an order of magnitude higher than the average gene signal, suggesting that human adipocytes express high endogenous levels of NEP mRNA. Real time PCR confirmed high levels of NEP mRNA in preadipocytes which increased 28 fold during differentiation and reached levels equivalent to the endogenous control, GAPDH, by 14 days. We created a diet induced model of obesity by feeding male C57BL/6J mice a high-fat diet, which resulted in decreased glucose tolerance and insulin resistance in obese mice. Plasma NEP levels measured after 15 weeks of feeding were significantly higher in obese mice (1642 [± 529]) pg/μl) compared to lean mice (820 [± 487] pg/μl) (p < 0.01). NEP levels increased 4- and 9-fold in epididymal and mesenteric fat in obese, compared to lean, mice. In a study of 318 healthy white European males, plasma NEP measured by activity assay was significantly higher in subjects with the metabolic syndrome (MetS) and levels increased progressively with increasing number of MetS components, being ~8-fold higher in those with 5 MetS components compared with those with none. NEP correlated with insulin, HOMA and BMI in all subjects. In conclusion, we have generated cell, murine and human data which suggest that NEP may have an important role in cardio-metabolic risk associated with insulin resistance, with the adipocyte as a major source of NEP. These findings indicate that NEP is a novel adipokine that links insulin resistance to vascular risk.

scholarly journals Gut microbiota regulates cardiac ischemic tolerance and aortic stiffness in obesity

2019 ◽  
Vol 317 (6) ◽  
pp. H1210-H1220 ◽  
Author(s):  
Micah L. Battson ◽  
Dustin M. Lee ◽  
Lance C. Li Puma ◽  
Kayl E. Ecton ◽  
Keely N. Thomas ◽  
...  
Keyword(s):  
Arterial Stiffness ◽  
Gut Microbiota ◽  
Infarct Size ◽  
Aortic Stiffness ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Obese Mice ◽  
Gut Permeability ◽  
Cardiovascular Pathology ◽  
Lv Mass

The gut microbiota has emerged as an important regulator of host physiology, with recent data suggesting a role in modulating cardiovascular health. The present study determined if gut microbial signatures could transfer cardiovascular risk phenotypes between lean and obese mice using cecal microbiota transplantation (CMT). Pooled cecal contents collected from obese leptin-deficient (Ob) mice or C57Bl/6j control (Con) mice were transplanted by oral gavage into cohorts of recipient Ob and Con mice maintained on identical low-fat diets for 8 wk ( n = 9–11/group). Cardiovascular pathology was assessed as the degree of arterial stiffness (aortic pulse wave velocity) and myocardial infarct size following a 45/120 min ex vivo global cardiac ischemia-reperfusion protocol. Gut microbiota was characterized by 16S rDNA sequencing, along with measures of intestinal barrier function and cecal short-chain fatty acid (SCFA) composition. Following CMT, the gut microbiota of recipient mice was altered to resemble that of the donors. Ob CMT to Con mice increased arterial stiffness, left ventricular (LV) mass, and myocardial infarct size, which were associated with greater gut permeability and reduced cecal SCFA concentrations. Conversely, Con CMT to Ob mice increased cecal SCFA, reduced LV mass, and attenuated myocardial infarct size, with no effects on gut permeability or arterial stiffness. Collectively, these data demonstrate that obesity-related changes in the gut microbiota, independent of dietary manipulation, regulate hallmark measures of cardiovascular pathology in mice and highlight the potential of microbiota-targeted therapeutics for reducing cardiovascular pathology and risk in obesity. NEW & NOTEWORTHY These data are the first to demonstrate that cecal microbiota transplantation (CMT) can alter cardiovascular pathology in lean and obese mice independent from alterations in dietary intake. Myocardial infarct size was reduced in obese mice receiving lean CMT and worsened in lean mice receiving obese CMT. Lean mice receiving obese CMT also displayed increased aortic stiffness. These changes were accompanied by alterations in short-chain fatty acids and gut permeability.

Extract of Schisandra chinensis fruit protects against metabolic dysfunction in high‐fat diet induced obese mice via FXR activation

2020 ◽  
Vol 34 (11) ◽  
pp. 3063-3077
Author(s):  
Ming Gu ◽  
Haiyan Song ◽  
Yiping Li ◽  
Yuwei Jiang ◽  
Yali Zhang ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Schisandra Chinensis ◽  
Metabolic Dysfunction ◽  
Obese Mice ◽  
High Fat

scholarly journals Mitochondrial and Metabolic Dysfunction in Renal Convoluted Tubules of Obese Mice: Protective Role of Melatonin

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e111141 ◽  
Author(s):  
Alessandra Stacchiotti ◽  
Gaia Favero ◽  
Lorena Giugno ◽  
Antonio Lavazza ◽  
Russel J. Reiter ◽  
...  
Keyword(s):  
Protective Role ◽  
Metabolic Dysfunction ◽  
Obese Mice ◽  
Convoluted Tubules

scholarly journals Glucocorticoid-Induced Metabolic Disturbances are Exacerbated in Obesity

2017 ◽  
Author(s):  
Innocence Harvey ◽  
Erin J. Stephenson ◽  
JeAnna R. Redd ◽  
Quynh T. Tran ◽  
Irit Hochberg ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Adult Male ◽  
Synergistic Effects ◽  
Lipolytic Enzyme ◽  
Metabolic Dysfunction ◽  
Obese Mice ◽  
Metabolic Disturbances ◽  
Diet Induced Obesity

AbstractObjective: To determine the effects of glucocorticoid-induced metabolic dysfunction in the presence of diet-induced obesity. Methods: C57BL/6J adult male lean and diet-induced obese mice were given dexamethasone for different durations and levels of hepatic steatosis, insulin resistance and lipolysis were determined. Results: Obese mice given dexamethasone had significant, synergistic effects on insulin resistance and markers of lipolysis, as well as hepatic steatosis. This was associated with synergistic transactivation of the lipolytic enzyme ATGL. Conclusions: The combination of chronically elevated glucocorticoids and obesity leads to exacerbations in metabolic dysfunction. Our findings suggest lipolysis may be a key player in glucocorticoid-induced insulin resistance and fatty liver in individuals with obesity.

scholarly journals Genetically obese mice do not show increased gut permeability or faecal bile acid hydrophobicity

2013 ◽  
Vol 110 (6) ◽  
pp. 1157-1164 ◽  
Author(s):  
Lotta K. Stenman ◽  
Reetta Holma ◽  
Helena Gylling ◽  
Riitta Korpela
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Intestinal Permeability ◽  
Low Grade ◽  
Obese Mice ◽  
Gut Permeability ◽  
Barrier Dysfunction ◽  
Gut Barrier ◽  
Genetic Obesity ◽  
Gut Barrier Function

Gut barrier dysfunction may lead to metabolic endotoxaemia and low-grade inflammation. Recent publications have demonstrated gut barrier dysfunction in obesity induced by a diet high in fat, and a pathogenetic role for luminal bile acids has been proposed. We aimed to investigate whether genetically obese mice develop increased gut permeability and alterations in luminal bile acids on a diet with a regular fat content. We used seven obese male ob/ob mice of C57BL/6J background and ten male wild-type (WT) mice of the same strain. Faeces were collected for bile acid analysis. Intestinal permeability was measured in an Ussing chamber upon euthanasia, using 4 kDa fluorescein isothiocyanate dextran, as per mille (‰, 1/1000) of translocated dextran. We analysed the liver expression of lipopolysaccharide-binding protein (LBP), as well as serum LBP (ELISA). Intestinal permeability was not affected by genetic obesity (jejunum: 0·234 (sem 0·04) ‰ for obese v. 0·225 (sem 0·03) ‰ for WT, P= 0·93; colon: 0·222 (sem 0·06) ‰ for obese v. 0·184 (sem 0·03) ‰ for WT, P= 0·86), nor was liver LBP expression (relative expression: 0·55 (sem 0·08) for obese v. 0·55 (sem 0·13) for WT, P= 0·70). Serum LBP was 2·5-fold higher in obese than in WT mice (P= 0·001). Obese mice had increased daily excretion of total bile acids, but their faecal bile acid hydrophobicity was unchanged. In conclusion, genetic obesity did not impair gut barrier function in mice on a regular chow diet, nor was faecal bile acid hydrophobicity affected.

scholarly journals Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability

Gut ◽  
2009 ◽  
Vol 58 (8) ◽  
pp. 1091-1103 ◽  
Author(s):  
P. D. Cani ◽  
S. Possemiers ◽  
T. Van de Wiele ◽  
Y. Guiot ◽  
A. Everard ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Obese Mice ◽  
Gut Permeability

scholarly journals Metformin Prevents Fatty Liver and Improves Balance of White/Brown Adipose in an Obesity Mouse Model by Inducing FGF21

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Eun Kyung Kim ◽  
Seung Hoon Lee ◽  
Joo Yeon Jhun ◽  
Jae Kyeong Byun ◽  
Jeong Hee Jeong ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Liver ◽  
The Body ◽  
Interleukin 17 ◽  
Metabolic Dysfunction ◽  
Obese Mice ◽  
High Fat ◽  
Gene Expressions ◽  
White Adipocyte ◽  
Brown Adipose

Obesity and its associated metabolic disorders are related to the onset of fatty liver and the balance of white adipose tissue (WAT) and brown adipose tissue (BAT). We hypothesized that metformin, an effective pharmacological treatment for type 2 diabetes, would inhibit white adipogenesis, fatty liver, and metabolic dysfunction. Metformin was treated daily for 14 weeks in a high-fat dieting C57BL/6J mice. Serum biomarkers were analyzed and protein level was assessed using confocal staining or flow cytometry. The development of lipid drops in the liver cells and white adipocyte was measured using hematoxylin and eosin or Oil Red O stains. Gene expressions were analyzed with quantitative real-time PCR. Metformin treatment decreased the body weight and improved the metabolic profile of obese mice. In obese mice, metformin also induced the expression of BAT-related markers and increased fibroblast growth factor (FGF) 21 expression in the liver and in white adipocyte. Metformin suppressed white adipocyte differentiation via induction of FGF21. Metformin improves Treg/Th17 balance in CD4+ T cells in mice with high-fat diet-induced obesity. Metformin also improves glucose metabolism and metabolic disorder. Interleukin-17 deficiency also decreases inflammation in mice. Therefore, metformin may be therapeutically useful for the treatment of obesity and metabolic dysfunction.

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