Lipotoxicity in obesity and diabetes-related cardiac dysfunction

Zlobine, Igor; Gopal, Keshav; Ussher, John R.

doi:10.1016/j.bbalip.2016.02.011

Cited by 138 publications

(97 citation statements)

References 160 publications

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“…Free fatty acid might induce the activation of NLRP3 inflammasome by ROS production and ER stress (Legrand-Poels et al, 2014). And intramyocellular lipid accumulation in cardiomyocytes has been frequently reported in diet-induced diabetes (Wolf et al, 2016; Zlobine et al, 2016). However, there was no evidence that intramyocellular lipid could promote the activation of intercellular NLRP3 inflammasome directly.…”

Section: The Activation Of Nlrp3 Inflammasome In Dcmmentioning

confidence: 99%

NLRP3 Inflammasome as a Molecular Marker in Diabetic Cardiomyopathy

et al. 2017

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Diabetic cardiomyopathy (DCM), a common consequence of longstanding diabetes mellitus, is initiated by death of cardiomyocyte. Hyperglycemia-induced reactive oxygen species (ROS) overproduction is a major contributor of the chronic low-grade inflammation that characterizes as the DCM. ROS may promote the activation of nucleotide-binding oligomerization domain like receptor (NLR) pyrin domain containing 3 (NLRP3) inflammasome, a novel regulator of inflammation and cell death, by nuclear factor-kB (NF-κB) and thioredoxin interacting/inhibiting protein (TXNIP). NLRP3 inflammasome regulates the death of cardiomyocyte and activation of fibroblast in DCM, which is involved in the structural and functional disorder of DCM. However, comprehensive understanding of molecular mechanisms linking NLRP3 inflammasome and disorder of cardiomyocyte and fibroblast in DCM is lacking. Here, we review the molecular mechanism(s) of NLRP3 inflammasome activation in response to hyperglycemia in DCM.

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Section: The Activation Of Nlrp3 Inflammasome In Dcmmentioning

confidence: 99%

NLRP3 Inflammasome as a Molecular Marker in Diabetic Cardiomyopathy

et al. 2017

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“…These pathologic alterations in cardiomyocytes are primarily triggered by systemic metabolic alterations such as hyperglycemia, hyper- and dyslipidemia, hyperinsulinemia and insulin resistance. Increased myocardial fatty acid uptake and generation of toxic lipid intermediates contribute to increased apoptosis, oxidative stress and LV dysfunction, and the cardiac manifestation of insulin resistance may contribute to mitochondrial dysfunction and uncoupling, oxidative stress, cardiac inefficiency, and myocardial energy depletion [43,44,45]. Thus, there is consistent evidence of a DC in rodent models of type 2 diabetes, and many findings have been reproduced in humans, strongly suggesting the existence of a human DC in type 2 diabetes.…”

Section: Preclinical Data On Diabetic Cardiomyopathymentioning

confidence: 99%

Diabetic Cardiomyopathy: Does the Type of Diabetes Matter?

Hölscher

Bode

Bugger

2016

IJMS

139

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In recent years, type 2 diabetes mellitus has evolved as a rapidly increasing epidemic that parallels the increased prevalence of obesity and which markedly increases the risk of cardiovascular disease across the globe. While ischemic heart disease represents the major cause of death in diabetic subjects, diabetic cardiomyopathy (DC) summarizes adverse effects of diabetes mellitus on the heart that are independent of coronary artery disease (CAD) and hypertension. DC increases the risk of heart failure (HF) and may lead to both heart failure with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). Numerous molecular mechanisms have been proposed to underlie DC that partially overlap with mechanisms believed to contribute to heart failure. Nevertheless, the existence of DC remains a topic of controversy, although the clinical relevance of DC is increasingly recognized by scientists and clinicians. In addition, relatively little attention has been attributed to the fact that both underlying mechanisms and clinical features of DC may be partially distinct in type 1 versus type 2 diabetes. In the following review, we will discuss clinical and preclinical literature on the existence of human DC in the context of the two different types of diabetes mellitus.

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“…Our results are in agreement with the earlier reports on significant elevation of FFAs in both HFD and HSD diet as compared to control fed. Chronically elevated FFAs may also impair insulin secretory function through toxic effects on pancreatic beta cells of metabolic changes seen in the adipose tissue, skeletal muscle and liver of insulin-resistant animals and subjects [25]. Liver Glycogen (mg/gm) 8.14 ± 0.8 6.91 ± 1.08 7.04 ± 0.74 Table 2: Tissue biochemical analysis HFD: High fructose diet, HSD: High sucrose diet fed group, Values are presented as mean ± SD drawn from pooled spillage of three cages of the same group and calculated for six animals per group.…”

Section: Discussionmentioning

confidence: 99%

Influence of Gut Microbiota on Inflammation and Pathogenesis of Sugar Rich Diet Induced Diabetes

Jena¹,

Prajapati²,

Mishra³

et al. 2016

Immunome Res

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Type 2 diabetes is characterized by peripheral insulin resistance. Besides immune and inflammatory mechanisms, other pathways involve interaction between gut microbiota and metabolic syndrome. The present study was designed to understand gut microbiota alteration following High Sugar Diet (HSD) and its effect on physiology and gastrointestinal immunology. Male wistar rats were fed with high fructose and HSD for 60 days. Composition of fecal microbiota by DGGE and proinflammatory cytokines in serum was investigated. Expressions of genes such as TLR2, TLR4 and NF-kB in various tissues were also studied. The bacteria coliforms and clostridium level were higher and Lactobacillus was lower in both sugar rich diet fed rats. Highly diverse and densely populated bands were observed in HSD group by DGGE fingerprint. The band profiles of sugar fed group have clustered together. Elevated mRNA expression of TLR2, TLR4, and NF-kB were observed in HSD groups. Increased inflammation was confirmed by blood and tissue biochemical assay and enhanced serum pro-inflammatory cytokines in HSD diet groups. Gut microbiota strongly influenced the metabolic profiling of individuals fed with high calorie intake. The diverse microbial population and increased coliforms and clostridium may affect host gene expression. Targeting TLRs and microbiota could be promising therapeutic approach.

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Lipotoxicity in obesity and diabetes-related cardiac dysfunction

Cited by 138 publications

References 160 publications

NLRP3 Inflammasome as a Molecular Marker in Diabetic Cardiomyopathy

NLRP3 Inflammasome as a Molecular Marker in Diabetic Cardiomyopathy

Diabetic Cardiomyopathy: Does the Type of Diabetes Matter?

Influence of Gut Microbiota on Inflammation and Pathogenesis of Sugar Rich Diet Induced Diabetes

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