Obesity and the Cardiorenal Metabolic Syndrome: Therapeutic Modalities and Their Efficacy in Improving Cardiovascular and Renal Risk Factors

Jindal, Ankur; Brietzke, Stephen; Sowers, James R.

doi:10.1159/000343803

Cited by 20 publications

(19 citation statements)

References 127 publications

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“…For example, there is evidence for a hypothalamus selective resistance to the metabolic actions leptin while its sympathetic nervous system activation effects on organs such as the kidneys are maintained [59]. The proinflammatory adipocytokine tumor necrosis factor α has been shown to promote macrophage recruitment and infiltration with consequent glomerular and tubulointerstitial inflammation as well as to promote upregulation of other inflammatory cytokines which promote kidney tissue fibrosis [64,65,66,67,68]. On the other end of the spectrum in obesity, there is a reduction in the anti-inflammatory adiponectin, and this reduction is associated with increases in albuminuria as well as kidney tissue fibrosis [62,65].…”

Section: Impact Of Obesity On the Kidney Distinct From That Of The Prmentioning

confidence: 99%

Insulin Resistance in Kidney Disease: Is There a Distinct Role Separate from That of Diabetes or Obesity

Whaley‐Connell¹,

Sowers

2017

Cardiorenal Med

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Insulin resistance is a central component of the metabolic dysregulation observed in obesity, which puts one at risk for the development of type 2 diabetes and complications related to diabetes such as chronic kidney disease. Insulin resistance and compensatory hyperinsulinemia place one at risk for other risk factors such as dyslipidemia, hypertension, and proteinuria, e.g., development of kidney disease. Our traditional view of insulin actions focuses on insulin-sensitive tissues such as skeletal muscle, liver, adipose tissue, and the pancreas. However, insulin also has distinct actions in kidney tissue that regulate growth, hypertrophy, as well as microcirculatory and fibrotic pathways which, in turn, impact glomerular filtration, including that governed by tubuloglomerular feedback. However, it is often difficult to discern the distinct effects of excess circulating insulin and impaired insulin actions, as exist in the insulin resistance individual, from the associated effects of obesity or elevated systolic blood pressure on the development and progression of kidney disease over time. Therefore, we review the experimental and clinical evidence for the distinct impact of insulin resistance on kidney function and disease.

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Section: Impact Of Obesity On the Kidney Distinct From That Of The Prmentioning

confidence: 99%

Insulin Resistance in Kidney Disease: Is There a Distinct Role Separate from That of Diabetes or Obesity

Whaley‐Connell¹,

Sowers

2017

Cardiorenal Med

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“…Conversely, a reduction in plasmin activation is also associated with reduced activation of transforming growth factor-␤ (TGF-␤), a molecule important for suppressing the proliferation and migration of smooth muscle cells that contributes to atherosclerotic lesion formation (71). This highlights the association of excess nutrient ingestion and obesity in driving CVD and CKD with various components of the CRS (29,70).…”

Section: Overnutrition Obesity and Cardiovascular Diseasesmentioning

confidence: 99%

“…Many persons with the metabolic syndrome will also have evidence of insipid renal and cardiovascular disease, and, thus, the CRS constellation. Overweight or obesity, especially abdominal obesity, caused by consumption of excess nutrients, especially high fructose and fat, has been increasingly implicated as an independent risk factor for development of diabetes, cardiovascular disease (CVD), and chronic kidney disease (CKD) (29). Indeed, obesity is a proinflammatory, prooxidative, and maladaptive immune state associated with the accumulation of dysfunctional adipose tissue, altered vascular homeostasis, and endothelial dysfunction, which predisposes individuals to CVD and CKD (30).…”

mentioning

confidence: 99%

Overnutrition, mTOR signaling, and cardiovascular diseases

Jia

Aroor

Martinez‐Lemus

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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101

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The prevalence of obesity and associated medical disorders has increased dramatically in the United States and throughout much of the world in the past decade. Obesity, induced by excess intake of carbohydrates and fats, is a major cause of Type 2 diabetes, hypertension, and the cardiorenal metabolic syndrome. There is emerging evidence that excessive nutrient intake promotes signaling through the mammalian target of rapamycin (mTOR), which, in turn, may lead to alterations of cellular metabolic signaling leading to insulin resistance and obesity-related diseases, such as diabetes, cardiovascular and kidney disease, as well as cancer. While the pivotal role of mTOR signaling in regulating metabolic stress, autophagy, and adaptive immune responses has received increasing attention, there remain many gaps in our knowledge regarding this important nutrient sensor. For example, the precise cellular signaling mechanisms linking excessive nutrient intake and enhanced mTOR signaling with increased cardiovascular and kidney disease, as well as cancer, are not well understood. In this review, we focus on the effects that the interaction between excess intake of nutrients and enhanced mTOR signaling have on the promotion of obesity-associated diseases and potential therapeutic strategies involving targeting mTOR signaling.

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“…Overweight or obesity, especially abdominal obesity, has become an independent risk factor for many diseases such as cardiovascular diseases, diabetes, multiple types of cancer and renal diseases [33,34]. It has been reported that mice consuming a Western diet manifested increased heart and vascular fibrosis which further resulted in cardiac hypertrophy and dysfunction [35].…”

Section: Discussionmentioning

confidence: 99%

CD38 Deficiency Protects Heart from High Fat Diet-Induced Oxidative Stress Via Activating Sirt3/FOXO3 Pathway

Wang

Huang

Yan

et al. 2018

Cell Physiol Biochem

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Background/Aims: Previous studies showed that CD38 deficiency protected heart from ischemia/reperfusion injury and high fat diet (HFD)-induced obesity in mice. However, the role of CD38 in HFD-induced heart injury remains unclear. In the present study, we have investigated the effects and mechanisms of CD38 deficiency on HFD-induced heart injury. Methods: The metabolites in heart from wild type (WT) and CD38 knockout (CD38^-/-) mice were examined using metabolomics analysis. Cell viability, lactate hydrogenase (LDH) release, super oxide dismutase (SOD) activity, reactive oxygen species (ROS) production, triglyceride concentration and gene expression were examined by biochemical analysis and QPCR. Results: Our results revealed that CD38 deficiency significantly elevated the intracellular glutathione (GSH) concentration and GSH/GSSG ratio, decreased the contents of free fatty acids and increased intracellular NAD⁺ level in heart from CD38^-/- mice fed with HFD. In addition, in vitro knockdown of CD38 significantly attenuated OA-induced cellular injury, ROS production and lipid synthesis. Furthermore, the expression of mitochondrial deacetylase Sirt3 as well as its target genes FOXO3 and SOD2 were markedly upregulated in the H9C2 cell lines after OA stimulation. In contrast, the expressions of NOX2 and NOX4 were significantly decreased in the cells after OA stimulation. Conclusion: Our results demonstrated that CD38 deficiency protected heart from HFD-induced oxidative stress via activating Sirt3/FOXO3-mediated anti-oxidative stress pathway.

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Obesity and the Cardiorenal Metabolic Syndrome: Therapeutic Modalities and Their Efficacy in Improving Cardiovascular and Renal Risk Factors

Cited by 20 publications

References 127 publications

Insulin Resistance in Kidney Disease: Is There a Distinct Role Separate from That of Diabetes or Obesity

Insulin Resistance in Kidney Disease: Is There a Distinct Role Separate from That of Diabetes or Obesity

Overnutrition, mTOR signaling, and cardiovascular diseases

CD38 Deficiency Protects Heart from High Fat Diet-Induced Oxidative Stress Via Activating Sirt3/FOXO3 Pathway

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