Obesity and Obesity-Initiated Metabolic Syndrome

Wahba, Ihab; Mak, Robert H.

doi:10.2215/cjn.04071206

Cited by 461 publications

(371 citation statements)

References 158 publications

(177 reference statements)

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“…Obesity contributes to the development of CKD through different mechanistic pathways that include glomerular hyperfiltration, activation of the renin-angiotensin system, insulin resistance, and direct lipotoxicity (30). There was no association between obesity and ESRD in this analysis, and obesity was associated with a lower risk for all-cause mortality.…”

Section: Discussionmentioning

confidence: 59%

Metabolic Syndrome, ESRD, and Death in CKD

Navaneethan

Schold

Kirwan

et al. 2013

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Previous studies reported an association between metabolic syndrome , incident CKD, and proteinuria. This study examined the associations between metabolic syndrome and its components with ESRD and death among those patients with stages 3 and 4 CKD (estimated GFR=15-59 ml/min per 1.73 m 2 ).Design, setting, participants, & measurements Patients with stages 3 and 4 CKD (n=25,868) who had data relating to metabolic syndrome and were followed in our health care system were identified using an electronic medical record-based registry. Cox proportional hazards models and competing risk analyses were used to study the associations between metabolic syndrome, its components (elevated BP, low HDL cholesterol, elevated serum triglycerides, impaired glucose metabolism, and obesity), and all-cause mortality and ESRD while adjusting for demographics, comorbid conditions, use of relevant medications, and renal function.Results Sixty percent of the study population (n=15,605) had metabolic syndrome. In the multivariate-adjusted analysis, presence of metabolic syndrome was associated with an increased risk for ESRD (hazard ratio=1.33, 95% confidence interval=1.08, 1.64) but not death (hazard ratio=1.04, 95% confidence interval=0.97, 1.12) during a mean follow-up of 2.3 years. Among the individual components of metabolic syndrome, impaired glucose metabolism, elevated triglycerides, and hypertension were associated with increased risk for ESRD, whereas low HDL cholesterol and impaired glucose metabolism were associated with higher risk of death.Conclusions Presence of metabolic syndrome is associated with ESRD but not death in patients with stages 3 and 4 CKD.Clin J Am Soc Nephrol 8: 945-952, 2013.

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Section: Discussionmentioning

confidence: 59%

Metabolic Syndrome, ESRD, and Death in CKD

Navaneethan

Schold

Kirwan

et al. 2013

Clinical Journal of the American Society of Nephrology

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“…1 In such patients, the risk of cardiovascular death is more than 10 times higher than that in subjects with normal kidney function. 2 Adipose tissue is currently considered to be not only a reservoir for storage of energy, but also an active endocrine organ producing several adipocytokines.…”

Section: Introductionmentioning

confidence: 99%

Potential impact of renin–angiotensin system inhibitors and calcium channel blockers on plasma high-molecular-weight adiponectin levels in hemodialysis patients

Nakagawa

Yao²,

Hirayama³

et al. 2011

Hypertens Res

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Although metabolic syndrome confers an increased risk of cardiovascular disease in the general population, little is known about the alteration of abdominal adiposity and its association with adipocytokines in hemodialysis patients. We investigated the plasma high-molecular-weight (HMW) adiponectin level and its relationship to visceral fat area (VFA) and various markers of atherosclerosis in hemodialysis patients. In a cross-sectional study, conventional cardiovascular risk factors, plasma total and HMW adiponectin, the number of components of the metabolic syndrome and, using computed tomography, the distribution of abdominal adiposity were assessed in 144 hemodialysis patients (90 men and 54 women; mean age, 60.7 years) and 30 age-and sex-matched patients with chronic kidney disease (CKD). Plasma HMW adiponectin levels in hemodialysis patients were significantly higher than those in patients with CKD, negatively associated with VFA and serum triglycerides and positively associated with plasma total adiponectin, as well as the HMW-to-total adiponectin ratio in men and women (all Po0.05) in a simple regression analysis. In a multiple regression analysis, VFA was a significant determinant of HMW adiponectin in hemodialysis patients. Furthermore, after adjustment for classical risk factors, HMW adiponectin levels were significantly higher in patients undergoing treatment with renin-angiotensin system inhibitors or calcium channel blockers compared with patients not undergoing such treatment. This study shows that plasma HMW adiponectin levels were negatively associated with VFA and positively associated with treatment with blockade of the renin-angiotensin system and of the calcium channel. Therefore, these drugs might be effective for improving adipocytokine-related metabolic abnormalities in hemodialysis patients.

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“…Conversely, treating dyslipidemia with statins preserves renal function (18,19). Interestingly, asides from their lipid lowering effects, statins also elicit antioxidant properties (10,20) that may contribute to the observed renoprotection.…”

Section: Discussionmentioning

confidence: 99%

Simvastatin attenuates oleic acid-induced oxidative stress through CREB-dependent induction of heme oxygenase-1 in renal proximal tubule cells

et al. 2015

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Background: Statins elicit antioxidant effects independently of their lipid-lowering properties. Heme oxygenase-1 (HO-1) induction may be a part of these pleiotropic effects, which are insufficiently described in the kidney. We hypothesize that simvastatin (SIM) transcriptionally activates HO-1 that protects renal proximal tubule cells from lipotoxic injury. Methods: Impact of SIM on 100 μmol/l oleic acid (OA)-mediated reactive oxygen species (ROS) production and consequent oxidative stress (4-hydroxynonenal (HNE) content) as well as cell injury/apoptosis (lactate dehydrogenase (LDH) release, caspase-3 activation) were determined in cultured renal proximal tubule (NRK52E) cells. Effect of SIM on the HO-1 promoter and its enhancer elements (antioxidant response element (ARE), CCAAT, AP1, and cAMP response element (CRE)) was also determined in reporter luciferase assays. Dominant-negative (dnMEK, M1CREB) and pharmacologic (H89) approaches were used to inhibit activation of extracellular signal regulated kinase (ERK), CREB, and protein kinase A (PKA), respectively. results: SIM dose-dependently activated the HO-1 promoter that was essential for protection against OA-dependent ROS production/oxidative stress and LDH release/caspase-3 activation. We found that the HO-1 promoter was induced through ERK and PKA-dependent activation of the CRE by SIM. conclusion: SIM may protect the kidney from adverse effects of circulating fatty acids by upregulating the antioxidant HO-1, aside from its well-described lipid-lowering effects.o besity is a growing problem among patients of all ages (1,2) that has a variety of effects on different organs including the kidney (3). Adverse effects of obesity are due to increased vascular reactivity, inflammation, and other factors called lipotoxicity (3). Obesity is associated with an elevation of circulating free fatty acids that are responsible for increased oxidative stress and subsequent lipotoxicity (3). Oleic acid (OA), a free fatty acid, is present in high concentration in the plasma of obese individuals (4). Previously, we showed that OA increases production of reactive oxygen species (ROS) that induces oxidative injury in renal proximal tubule cells (5).Statins-such as simvastatin (SIM)-are extensively used to lower dyslipidemia in children (6). Statins are not only lower lipids but also shown to exert "pleiotropic" effects that are not due to their lipid-lowering activity (7). For example, SIM transcriptionally activates the antioxidant HO-1 gene in the liver and NIH3T3 cells (8,9). It is plausible that such antioxidant properties can be used to diminish lipotoxic oxidative stress, caused by obesity. HO-1 induction-dependent renoprotective effects of SIM in a rat model of acute ischemia/reperfusion injury are noted (10) but the underlying mechanism and its potential role in obesity is unknown.Heme oxygenase-1 (HO-1) elicits adaptive responses against oxidative stress in the kidney (11). Oxidative stress transcriptionally induces the HO-1 promoter mostly via the antioxidant respon...

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Obesity and Obesity-Initiated Metabolic Syndrome

Cited by 461 publications

References 158 publications

Metabolic Syndrome, ESRD, and Death in CKD

Metabolic Syndrome, ESRD, and Death in CKD

Potential impact of renin–angiotensin system inhibitors and calcium channel blockers on plasma high-molecular-weight adiponectin levels in hemodialysis patients

Simvastatin attenuates oleic acid-induced oxidative stress through CREB-dependent induction of heme oxygenase-1 in renal proximal tubule cells

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