Obesity and Inflammatory Vasculopathy

Heusch, Gerd

doi:10.1161/atvbaha.111.232264

Cited by 8 publications

(6 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is commonly recognized by the presence of crown-like structures that appear between adipocytes 18, 33, 34 . In humans, obesity is similarly associated with adipose tissue inflammation, and weight loss interventions such as bariatric surgery improve endothelial function 35, 36 . Therefore, we examined adipose tissue inflammation in WT and eNOS-TG mice after 6 weeks of high fat diet.…”

Section: Resultsmentioning

confidence: 99%

Overexpression of Endothelial Nitric Oxide Synthase Prevents Diet-Induced Obesity and Regulates Adipocyte Phenotype

Sansbury

Cummins

Tang

et al. 2012

Circulation Research

141

136

View full text Add to dashboard Cite

Rationale Endothelial dysfunction is a characteristic feature of diabetes and obesity in animal models and humans. Deficits in nitric oxide production by endothelial nitric oxide synthase (eNOS) are associated with insulin resistance, which is exacerbated by high fat diet. Nevertheless, the metabolic effects of increasing eNOS levels have not been studied. Objective The current study was designed to test whether overexpression of eNOS would prevent diet-induced obesity and insulin resistance. Methods and Results In db/db mice and in high fat-fed wild-type (WT) C57BL/6J mice, the abundance of eNOS protein in adipose tissue was decreased without significant changes in eNOS levels in skeletal muscle or aorta. Mice overexpressing eNOS (eNOS-TG mice) were resistant to diet-induced obesity and hyperinsulinemia, although systemic glucose intolerance remained largely unaffected. In comparison with WT mice, high fat-fed eNOS-TG mice displayed a higher metabolic rate and attenuated hypertrophy of white adipocytes. Overexpression of eNOS did not affect food consumption or diet-induced changes in plasma cholesterol or leptin levels, yet plasma triglycerides and fatty acids were decreased. Metabolomic analysis of adipose tissue indicated that eNOS overexpression primarily affected amino acid and lipid metabolism; subpathway analysis suggested changes in fatty acid oxidation. In agreement with these findings, adipose tissue from eNOS-TG mice showed higher levels of PPAR-α and PPAR–γ gene expression, elevated abundance of mitochondrial proteins, and a higher rate of oxygen consumption. Conclusions These findings demonstrate that increased eNOS activity prevents the obesogenic effects of high fat diet without affecting systemic insulin resistance, in part, by stimulating metabolic activity in adipose tissue.

show abstract

Section: Resultsmentioning

confidence: 99%

Overexpression of Endothelial Nitric Oxide Synthase Prevents Diet-Induced Obesity and Regulates Adipocyte Phenotype

Sansbury

Cummins

Tang

et al. 2012

Circulation Research

141

136

View full text Add to dashboard Cite

show abstract

“…Chronic low-grade inflammation can be both a cause and consequence of endothelial dysfunction, and the two appear to be tightly linked [65]. Since type 2 diabetes is highly associated with obesity, the metabolic role of adipose tissue potentiates the adverse effects on the vasculature [31, 98, 99]. Adipose tissue secretes a range of proinflammatory molecules, which lead to systemic inflammation and participate in the cross talk between adipose stores and the vascular wall (see Ref.…”

Section: Perspectivesmentioning

confidence: 99%

The link between metabolic abnormalities and endothelial dysfunction in type 2 diabetes: an update

2011

View full text Add to dashboard Cite

Despite abundant clinical evidence linking metabolic abnormalities to diabetic vasculopathy, the molecular basis of individual susceptibility to diabetic vascular complications is still largely undetermined. Endothelial dysfunction in diabetes-associated vascular complications is considered an early stage of vasculopathy and has attracted considerable research interests. Type 2 diabetes is characterized by metabolic abnormalities, such as hyperglycemia, excess liberation of free fatty acids (FFA), insulin resistance and hyperinsulinemia. These abnormalities exert pathological impact on endothelial function by attenuating endothelium-mediated vasomotor function, enhancing endothelial apoptosis, stimulating endothelium activation/endothelium–monocyte adhesion, promoting an atherogenic response and suppressing barrier function. There are multiple signaling pathways contributing to the adverse effects of glucotoxicity on endothelial function. Insulin maintains the normal balance for release of several factors with vasoactive properties. Abnormal insulin signaling in the endothelium does not affect the whole-body glucose metabolism, but impairs endothelial response to insulin and accelerates atherosclerosis. Excessive level of FFA is implicated in the pathogenesis of insulin resistance. FFA induces endothelial oxidative stress, apoptosis and inflammatory response, and inhibits insulin signaling. Although hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia independently contribute to endothelial dysfunction via various distinct mechanisms, the mutual interactions may synergistically accelerate their adverse effects. Oxidative stress and inflammation are predicted to be among the first alterations which may trigger other downstream mediators in diabetes associated with endothelial dysfunction. These mechanisms may provide insights into potential therapeutic targets that can delay or reverse diabetic vasculopathy.

show abstract

“…Obesity is among the major risk factors for myocardial dysfunction and remodeling, leading to high cardiovascular morbidity and mortality [1–4]. In addition to genetic predisposition, both clinical and experimental evidence has revealed a rather pivotal role of excessive fat and caloric intake in the onset of obesity and accompanied inflammation, cardiac hypertrophy, myocardial dysfunction, and mitochondrial injury [5–7].…”

Section: Introductionmentioning

confidence: 99%

Adiponectin knockout accentuates high fat diet-induced obesity and cardiac dysfunction: Role of autophagy

Guo

Zhang

Turdi

et al. 2013

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

147

View full text Add to dashboard Cite

Adiponectin (APN), an adipose-derived adipokine, offers cardioprotective effects although the precise mechanism of action remains unclear. This study was designed to examine the role of APN in high fat diet-induced obesity and cardiac pathology. Adult C57BL/6 wild-type and APN knockout mice were fed a low or high fat diet for 22 weeks. After 40 day feeding, mice were treated with 2 mg/kg rapamycin or vehicle every other day for 42 days on respective fat diet. Cardiomyocyte contractile and Ca2+ transient properties were evaluated. Myocardial function was evaluated using echocardiography. Dual energy X-ray absorptiometry was used to evaluate adiposity. Energy expenditure, metabolic rate and physical activity were monitored using a metabolic cage. Lipid deposition, serum triglyceride, glucose tolerance, markers of autophagy and fatty acid metabolism including LC3, p62, Beclin-1, AMPK, mTOR, fatty acid synthase (FAS) were evaluated. High fat diet intake induced obesity, systemic glucose intolerance, cardiac hypertrophy, dampened metabolic ability, cardiac and intracellular Ca2+ derangements, the effects of which were accentuated by APN knockout. Furthermore, APN deficiency augmented high fat diet-induced upregulation in the autophagy adaptor p62 and the decline in AMPK without affecting high fat diet-induced decrease in LC3II and LC3II-to-LC3I ratio. Neither high fat diet nor APN deficiency altered Beclin-1. Interestingly, rapamycin negated high fat diet-induced/APN-deficiency-accentuated obesity, cardiac hypertrophy and contractile dysfunction as well as AMPK dephosphorylation, mTOR phosphorylation and p62 buildup. Our results collectively revealed that APN deficiency may aggravate high fat diet-induced obesity, metabolic derangement, cardiac hypertrophy and contractile dysfunction possibly through decreased myocardial autophagy.

show abstract

Obesity and Inflammatory Vasculopathy

Cited by 8 publications

References 25 publications

Overexpression of Endothelial Nitric Oxide Synthase Prevents Diet-Induced Obesity and Regulates Adipocyte Phenotype

Overexpression of Endothelial Nitric Oxide Synthase Prevents Diet-Induced Obesity and Regulates Adipocyte Phenotype

The link between metabolic abnormalities and endothelial dysfunction in type 2 diabetes: an update

Adiponectin knockout accentuates high fat diet-induced obesity and cardiac dysfunction: Role of autophagy

Contact Info

Product

Resources

About