Lipotoxic and inflammatory phenotypes in rats with uncontrolled metabolic syndrome and nephropathy

2007 ◽  
Vol 293 (3) ◽  
pp. F670-F679 ◽  
Author(s):  
Jesus Dominguez ◽  
Pengfei Wu ◽  
C. Subah Packer ◽  
Constance Temm ◽  
Katherine J. Kelly
Keyword(s):  
Heart Failure ◽  
Metabolic Syndrome ◽  
Renal Injury ◽  
Lipid Accumulation ◽  
Inflammatory Responses ◽  
Overt Nephropathy ◽  
Renal Inflammation ◽  
The Metabolic Syndrome ◽  
Renal Size ◽  
Inflammatory Phenotypes

Anomalous inflammatory responses triggered by the metabolic syndrome cause renal injury. This discovery links renal lipid accumulation with lipotoxicity to inflammation and may explain the insidious fibrosis and cellular decay characteristic of nephropathy in the metabolic syndrome. However, it is not clear whether control of inflammation protects the kidney independently of lipid accumulation, which is a required step for lipotoxicity in hyperglycemia and dyslipidemia. We hypothesized that in rats with the metabolic syndrome, and overt nephropathy, treatment with mycophenolate mofetil (MMF; 10 mg·kg−1·day−1 ip for 14 wk) would reduce the abnormal renal lipid depots and limit renal inflammation and injury. We studied groups of lean and obese F1 hybrid Zucker fatty diabetic/spontaneous hypertensive heart failure (ZS) rats. MMF did not affect lean rats. In obese ZS rats, MMF did not change severe hyperglycemia or the higher kidney loads of unutilized lipid and peroxidation products. Nonetheless, MMF dramatically reduced diabetes/obesity-derived systemic and renal inflammation, limited renal size, hyperfiltration, and fibrosis. These data indicate that in rats, anti-inflammatory therapy presumably acting downstream, and independently of lipotoxicity, can effectively limit renal injury and fibrosis.

scholarly journals Prognostic Impact of Metabolic Syndrome in Patients With Heart Failure: A Meta-Analysis of Observational Studies

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhuo-Ming Huang ◽  
Wen-Rong Chen ◽  
Qi-Wen Su ◽  
Zhuo-Wen Huang
Keyword(s):  
Heart Failure ◽  
Metabolic Syndrome ◽  
Cardiovascular Mortality ◽  
Cardiovascular Events ◽  
Observational Studies ◽  
Meta Analysis ◽  
Prognostic Impact ◽  
The Metabolic Syndrome ◽  
All Cause Mortality ◽  
The Impact

Background: The metabolic syndrome (MS) is significantly associated with the risk of incident heart failure (HF). However, there are still great controversies about the impact of MS on the prognosis in patients with established HF. This meta-analysis aimed to ascertain the effect of MS on the prognosis in patients with HF.Methods: We searched multiple electronic databases, including PubMed, Opengrey, EMBASE, and Cochran Library, for potential studies up to February 15, 2021. Observational studies that reported the impact of MS on the prognosis in patients with established HF were included for meta-analysis.Results: Ten studies comprising 18,590 patients with HF were included for meta-analysis. The median follow-up duration of the included studies was 2.4 years. Compared with HF patients without MS, the risk of all-cause mortality and cardiovascular mortality was not increased in HF with MS (HR = 1.04, 95% CI = 0.88–1.23 for all-cause mortality; HR = 1.66, 95% CI = 0.56–4.88 for cardiovascular mortality, respectively). However, there was a significant increase in composited cardiovascular events in the HF patients with MS compared with those without MS (HR = 1.73, 95% CI = 1.23–2.45).Conclusions: In patients with established HF, the presence of MS did not show an association on the risk of all-cause mortality or cardiovascular mortality, while it may increase the risk of composite cardiovascular events.

The metabolic syndrome in heart failure: insights to specific mechanisms

2019 ◽  
Vol 25 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Paola Gargiulo ◽  
Fabio Marsico ◽  
Francesco Renga ◽  
Simona Dell’Aversana ◽  
Immacolata Esposito ◽  
...  
Keyword(s):  
Heart Failure ◽  
Metabolic Syndrome ◽  
The Metabolic Syndrome

Cardiac and metabolic changes in long-term high fructose-fat fed rats with severe obesity and extensive intramyocardial lipid accumulation

2010 ◽  
Vol 298 (6) ◽  
pp. R1560-R1570 ◽  
Author(s):  
Lene N. Axelsen ◽  
Jacob B. Lademann ◽  
Jørgen S. Petersen ◽  
Niels-Henrik Holstein-Rathlou ◽  
Thorkil Ploug ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Animal Model ◽  
Glucose Tolerance ◽  
Lipid Accumulation ◽  
Severe Obesity ◽  
Ischemia Reperfusion ◽  
Western World ◽  
Cardiac Complications ◽  
The Metabolic Syndrome

Metabolic syndrome and obesity-related diseases are affecting more and more people in the Western world. The basis for an effective treatment of these patients is a better understanding of the underlying pathophysiology. Here, we characterize fructose- and fat-fed rats (FFFRs) as a new animal model of metabolic syndrome. Sprague-Dawley rats were fed a 60 kcal/100 kcal fat diet with 10% fructose in the drinking water. After 6, 12, 18, 24, 36, and 48 wk of feeding, blood pressure, glucose tolerance, plasma insulin, glucose, and lipid levels were measured. Cardiac function was examined by in vivo pressure volume measurements, and intramyocardial lipid accumulation was analyzed by confocal microscopy. Cardiac AMP-activated kinase (AMPK) and hepatic phospho enolpyruvate carboxykinase (PEPCK) levels were measured by Western blotting. Finally, an ischemia-reperfusion study was performed after 56 wk of feeding. FFFRs developed severe obesity, decreased glucose tolerance, increased serum insulin and triglyceride levels, and an initial increased fasting glucose, which returned to control levels after 24 wk of feeding. The diet had no effect on blood pressure but decreased hepatic PEPCK levels. FFFRs showed significant intramyocardial lipid accumulation, and cardiac hypertrophy became pronounced between 24 and 36 wk of feeding. FFFRs showed no signs of cardiac dysfunction during unstressed conditions, but their hearts were much more vulnerable to ischemia-reperfusion and had a decreased level of phosphorylated AMPK at 6 wk of feeding. This study characterizes a new animal model of the metabolic syndrome that could be beneficial in future studies of metabolic syndrome and cardiac complications.

scholarly journals Sleeping Beauty or the Beast? – The Metabolic Syndrome from an Obstructive Sleep Apnoea Perspective

2010 ◽  
Vol 9 (1) ◽  
pp. 12 ◽  
Author(s):  
Lise Tarnow ◽  
Brigitte Klinkenbijl ◽  
Holger Woehrle ◽  
◽  
◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Obstructive Sleep Apnoea ◽  
Reduce Blood Pressure ◽  
Sleep Apnoea ◽  
Sleeping Beauty ◽  
The Metabolic Syndrome ◽  
Home Based ◽  
Obstructive Sleep

Obstructive sleep apnoea (OSA) is a significant health issue. Patients with cardiovascular disease as well as patients with diabetes have a high prevalence of OSA, and the prevalence of coronary heart disease, heart failure, stroke and diabetes is increased in patients with obstructive sleep apnoea. Physiological responses to OSA include sympathetic activation, neurohumoral changes and inflammation, all of which are precursors for cardiovascular disease and diabetes. International guidelines are starting to recognise the importance of OSA for patients with cardiovascular conditions such as heart failure and hypertension. Diagnosis is important, and home-based sleep testing devices can facilitate this process. Treating OSA with continuous positive airway pressure (CPAP) has been shown to reduce blood pressure (BP) in patients with hypertension, but more research is needed to determine which components of the metabolic syndrome respond best to the addition of CPAP therapy.

Abstract 1124: CD40L Induces Inflammation in Adipose Tissue - a Potential Link Between the Metabolic Syndrome and Atherosclerosis

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Anna Missiou ◽  
Isabel Platzer ◽  
Sandra Ernst ◽  
Uwe Schonbeck ◽  
Peter Libby ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Endothelial Cells ◽  
Adipose Tissue ◽  
Cardiovascular Risk ◽  
Inflammatory Cytokine ◽  
Inflammatory Responses ◽  
Human Adipose Tissue ◽  
Cell Types ◽  
High Cardiovascular Risk ◽  
The Metabolic Syndrome

Background: CD40L figures prominently as marker and mediator of atherosclerosis and its clinical complications. Recent data also demonstrate an association between CD40L and the metabolic syndrome. In the light of these data we hypothesized a functional pro-inflammatory role of CD40L in adipose tissue that provokes systemic pro-inflammatory responses and potentially mediates some of the high cardiovascular risk associated with the metabolic syndrome. Methods and Results: Adipocytes and preadipocytes isolated from adipose tissue obtained from bariatic surgery did not express CD40L but its receptor CD40 as assessed by PCR and immunohistochemistry. Furthermore, sections of human adipose tissue from obese donors contained more macrophages and T cells colocalizing with CD40L than those from lean controls. Stimulation of both adipocytes and preadipocytes with recombinant CD40L resulted in a concentration- and time-dependent release of the pro-inflammatory cytokine IL-6, the chemokines MCP -1 and IL-8 as well as the inhibitor of fibrinolysis PAI-1 into the supernatant as quantified by ELISA. Membranes isolated from a Murine cell line overexpressing human CD40L reproduced these pro-inflammatory effects compared to respective controls. Interestingly, fenofibrate but neither rosiglitazone, metformin, nor atorvastatin attenuated the CD40L-inducible expression of these pro-atherogenic mediators. Finally, supernatants from adipocytes and preadipocytes stimulated with CD40L activated endothelial cells and macrophages, typical cell types resident in atherosclerotic lesions, as assessed by FACS for tissue factor, Mac-1, and ICAM-1, respectively. Conclusions: Our data suggest that CD40L induces inflammatory cytokine production in adipose tissue resulting in activation of endothelial cells and macrophages. This new mechanism may contribute to the high cardiovascular risk of patients suffering from the metabolic syndrome.

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