Perivascular adipose tissue-derived leptin promotes vascular smooth muscle cell phenotypic switching via p38 mitogen-activated protein kinase in metabolic syndrome rats

Li, Hao; Wang, Yaping; Zhang, Lina; Tian, Gang

doi:10.1177/1535370214527903

Cited by 40 publications

(33 citation statements)

References 35 publications

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“…Interestingly, ROS may actually stimulate insulin sensitivity and improve metabolic homeostasis (30). In PAT, the adiponectin to leptin ratio has been shown to be cardioprotective with greater adiponectin and lower leptin being associated with improved endothelial function (23). Here, the adiponectin to leptin ratio was improved with Ex only.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Diet versus Exercise on Metabolic Function and Gut Microbiota in Obese Rats

Welly

Liu

Zidon

et al. 2016

Medicine &Amp; Science in Sports &Amp; Exercise

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Cardiometabolic impairments that begin early in life are particularly critical, as they often predict metabolic dysfunction into adulthood. Obesity, high-fat diet (HFD), and inactivity are all associated with adipose tissue (AT) inflammation and insulin resistance (IR), major predictors of metabolic dysfunction. Recent evidence also has associated the gut microbiome with cardiometabolic health. PURPOSE Compare equal energy deficits induced by exercise and caloric reduction on cardiometabolic disease risk parameters including AT inflammation, IR and gut microbiota changes during HFD consumption. METHODS Obesity-prone rats fed HFD were exercise trained (Ex, n=10) or weight-matched to Ex via caloric reduction while kept sedentary (WM, n=10), and compared to ad libitum HFD-fed (Sed, n=10) rats for IR, systemic energetics and spontaneous physical activity (SPA), adiposity, and fasting metabolic parameters. Visceral, subcutaneous, periaortic, and brown AT, liver, aorta, and cecal digesta were examined. RESULTS Despite identical reductions in adiposity, Ex, but not WM, improved IR, increased SPA by ~26% (p<0.05 compared to WM and Sed), and reduced LDL cholesterol (p<0.05 compared to Sed). WM and Ex both reduced inflammatory markers in all AT depots and aorta, while only Ex increased indicators of mitochondrial function in brown AT. Ex significantly increased the relative abundance of cecal Streptococcaceae and decreased S24-7 and one undefined genus in Rikenellacea; WM induced similar changes that did not reach statistical significance. CONCLUSIONS Both Ex and WM reduced AT inflammation across depots, while Ex caused more robust changes to gut microbial communities, improved IR, increased fat oxidation, increased SPA, and increased indices of brown AT mitochondrial function. Our findings add to the growing body of literature indicating that there are weight-loss independent metabolic benefits of exercise.

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Section: Discussionmentioning

confidence: 99%

Comparison of Diet versus Exercise on Metabolic Function and Gut Microbiota in Obese Rats

Welly

Liu

Zidon

et al. 2016

Medicine &Amp; Science in Sports &Amp; Exercise

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“…The PVAT from the descending thoracic aorta of the mice was dissected and incubated with DMEM for 24 h. The medium was collected as conditioned medium (CM) [19]. In some experiments, PVAT-CM from different groups was pretreated first with palmitic acid (PA, 500 uM) or irisin (50 nM) and then pretreated with a varieties of inhibitors individually: HO-1 inhibitor stannous protoporphyrin (SnPP, 20 uM; Frontier Scientific, Inc., Logan, UT, USA), adiponectin receptor blocking peptide (ACRP-30 N-20, 0.4 μg/mL; Santa Cruz Biotechnology, USA), AMPK inhibitor Compound C (20 µM; Merck, Darmstadt, Germany) or eNOS inhibitor L-NAME (10 -4 M; Sigma) individually for 2 h. In brief, PVAT-CM was divided into different groups and a variety of inhibitors were individually added into the different groups.…”

Section: Methodsmentioning

confidence: 99%

Irisin Regulates Heme Oxygenase-1/Adiponectin Axis in Perivascular Adipose Tissue and Improves Endothelial Dysfunction in Diet-Induced Obese Mice

Hou¹,

Du²,

Han

et al. 2017

Cell Physiol Biochem

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Aims: To determine whether irisin could improve endothelial dysfunction by regulating heme oxygenase-1(HO-1)/adiponectin axis in perivascular adipose tissue (PVAT) in obesity. Methods: Male C57BL/6 mice were fed with a high-fat diet (HFD) with or without irisin treatment. Endothelium-dependent vasorelaxation of the thoracic aorta with or without PVAT (PVAT+ or PVAT–) was determined. Western blot was employed to determine the levels of HO-1 and adiponectin in PVAT. UCP-1, Cidea, and TNF-α gene expression in PVAT were tested by real-time PCR. Results: The presence of PVAT significantly impaired endothelial function in the HFD mice. Treatment of HFD mice with irisin significantly restored this impairment and improved endothelial function in vivo or ex vivo. Incubated aortic rings (PVAT-) with PVAT-derived conditioned medium (CM) from HFD mice impaired endothelial function in control mice. This impairment was prevented by incubating the aortic rings (PVAT-) from HFD mice with PVAT-derived CM from irisin. However, the beneficial effects were partly attenuated in the presence of HO-1 inhibitor and adiponectin receptor blocking peptide. Treatment of HFD mice with irisin significantly increased NO production, protein levels of HO-1 and adiponectin, mRNA expressions of UCP-1 and Cidea, and decreased superoxide production and TNF-α expression in PVAT. Conclusion: Irisin improved endothelial function by modulating HO-1/ adiponectin axis in PVAT in HFD-induced obese mice. These findings suggest that regulating PVAT function may be a potential mechanism by which irisin improves endothelial function in obesity.

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“…Whereas collagen provides the aorta with mechanical strength (35), we found here that combining physical training with an HFD reduced the aortic content of these fibers [Figure 1F; p < 0.05 (first and second analyses)]. Since this fact could be related to tissue remodeling, myofibroblasts were enumerated (36). Thus, we found that physical training increased the number of positive α-actin cells among rats that were fed an HFD [Figures 1G,H; p < 0.05 (first analysis); p < 0.001 (second analysis)].…”

Section: Resultsmentioning

confidence: 94%

High-Fat and Fat-Enriched Diets Impair the Benefits of Moderate Physical Training in the Aorta and the Heart in Rats

et al. 2017

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AimMillions of people die each year due to cardiovascular disease (CVD). A Western lifestyle not only fuses a significant intake of fat with physical inactivity and obesity but also promotes CVD. Recent evidence suggests that dietary fat intake impairs the benefits of physical training. We investigated whether aerobic training could reverse the adverse effects of a high-fat diet (HFD) on the aorta. Then, we explored whether this type of exercise could reverse the damage to the heart that is imposed by fat-enriched diet (FED).MethodsRats were randomly assigned to two experiments, which lasted 8 weeks each. First, rats swam for 60 min and were fed either a regular diet [standard diet (STD)] or an HFD. After aortic samples had been collected, the rats underwent a histopathological analysis for different biomarkers. Another experiment subjected rats that were fed either an STD or an FED to swimming for 20 or 90 min.ResultsThe first experiment revealed that rats that were subjected to an HFD-endured increased oxidative damage in the aorta that exercises could not counteract. Together with increased cyclooxygenase 2 expression, an HFD in combination with physical training increased the number of macrophages. A reduction in collagen fibers with an increased number of positive α-actin cells and expression of matrix metalloproteinase-2 occurred concomitantly. Upon analyzing the second experiment, we found that physically training rats that were given an FED for 90 min/day decreased the cardiac adipose tissue density, although it did not protect the heart from fat-induced oxidative damage. Even though the physical training lowered cholesterol levels that were promoted by the FED, the levels were still higher than those in the animals that were given an STD. Feeding rats an FED impaired the swimming protocol’s effects on lowering triglyceride concentration. Additionally, exercise was unable to reverse the fat-induced deregulation in hepatic antioxidant and lipid peroxidation activities.ConclusionOur findings reveal that an increased intake of fat undermines the potential benefits of physical exercise on the heart and the aorta.

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Perivascular adipose tissue-derived leptin promotes vascular smooth muscle cell phenotypic switching via p38 mitogen-activated protein kinase in metabolic syndrome rats

Cited by 40 publications

References 35 publications

Comparison of Diet versus Exercise on Metabolic Function and Gut Microbiota in Obese Rats

Comparison of Diet versus Exercise on Metabolic Function and Gut Microbiota in Obese Rats

Irisin Regulates Heme Oxygenase-1/Adiponectin Axis in Perivascular Adipose Tissue and Improves Endothelial Dysfunction in Diet-Induced Obese Mice

High-Fat and Fat-Enriched Diets Impair the Benefits of Moderate Physical Training in the Aorta and the Heart in Rats

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