Role of uncoupling protein 2 (UCP2) expression and 1α, 25‐dihydroxyvitamin D
            3
            in modulating adipocyte apoptosis

Mitochondrial dysfunction causes severe cellular derangements potentially underlying tissue injury and consequent diseases. Evidence of a direct involvement of mitochondrial dysfunction in hypertensive target organ damage is still poor. The gene encoding Uncoupling Protein 2 (UCP2), a inner mitochondrial membrane protein, maps inside stroke QTL/STR1 in stroke prone spontaneously hypertensive rat (SHRSP). We explored the role of UCP2 in stroke pathogenesis of SHRSP. Male SHRSP, stroke resistant SHR (SHRSR) and reciprocal STR1/congenic rats were fed with stroke permissive Japanese style diet (JD). A group of SHRSP received JD plus fenofibrate (150 mg/kg/die). Rats were sacrificed at stroke occurrence. Additional SHRSR and SHRSP rats were sacrificed at 1, 3, 6, 12 months of age upon regular diet. SBP, BW, proteinuria, stroke signs were monitored. Brains were used for molecular analysis (UCP2 gene and protein expression, Nf-kB protein expression, oxidative stress quantification) and for histological analyses. As a result, brain UCP2 expression was reduced to 20% by JD only in SHRSP (showing 100% stroke occurrence by 7 weeks of JD). Fenofibrate protected SHRSP from stroke and upregulated brain UCP2 (+ 100%). Congenic rats carrying STR1/QTL showed increased (+100%) brain UCP2 expression, as compared to SHRSP, when resistant to stroke, and, viceversa, decreased (-50%) brain UCP2 levels, as compared to SHRSR, when susceptible to stroke. Brain UCP2 expression progressively decreased with aging only in SHRSP, down to 15% level at one year of age (when SHRSP showed spontaneous stroke). Both brain Nf-kB expression and oxidative stress levels increased when UCP2 expression was downregulated, and viceversa. Histological analysis showed both ischemic and haemorrhagic lesions at stroke occurrence. Our results highlight a role of UCP2 in stroke predisposition associated to hypertension in an animal model of complex human disease.

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Role of Positively Charged Residues of the Second Transmembrane Domain in the Ion Transport Activity and Conformation of Human Uncoupling Protein-2

Biochemistry ◽

10.1021/acs.biochem.5b00177 ◽

2015 ◽

Vol 54 (14) ◽

pp. 2303-2313 ◽

Cited By ~ 5

Author(s):

Tuan Hoang ◽

Tijana Matovic ◽

James Parker ◽

Matthew D. Smith ◽

Masoud Jelokhani-Niaraki

Keyword(s):

Ion Transport ◽

Transmembrane Domain ◽

Uncoupling Protein ◽

Uncoupling Protein 2 ◽

Transport Activity ◽

Charged Residues ◽

Positively Charged

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Role of Uncoupling Protein 2 in Pancreatic _ Cell Function

Oxidative Stress and Disease - Oxidative Stress and Inflammatory Mechanisms in Obesity, Diabetes, and the Metabolic Syndrome ◽

10.1201/9781420043792.ch13 ◽

2007 ◽

pp. 211-224

Author(s):

Jingyu Diao ◽

Catherine Chan ◽

Michael Wheeler

Keyword(s):

Cell Function ◽

Uncoupling Protein ◽

Uncoupling Protein 2 ◽

Pancreatic Cell

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Association Study of Candidate Gene Uncoupling Protein 2 (UCP2) with Type 2 Diabetes Mellitus in the Different Population Groups of Jammu Region

Biosciences Biotechnology Research Asia ◽

10.13005/bbra/2751 ◽

2019 ◽

Vol 16 (2) ◽

pp. 351-357

Author(s):

Sunil Raina ◽

Roopali Fotra

Keyword(s):

Diabetes Mellitus ◽

Metabolic Disorders ◽

Uncoupling Protein ◽

Molecular Genetic ◽

Promoter Polymorphism ◽

Uncoupling Protein 2 ◽

Population Groups ◽

Allelic Odds Ratio

Diabetes Mellitus is a group of metabolic disorders characterized by hyperglycaemic resulting from the defects of insulin secretion, insulin action or both. The present study was conducted in order to know the molecular genetic cause of the T2DM patients belonging to the Jammu region of J&K State. Many genes have been known to be linked with the onset and progression of the T2DM therefore the present data represents the role of one of the genes Uncoupling protein 2 (UCP2) known to be strongly associated with T2DM was selected. A total of 250 confirmed cases & controls samples belonging to four population groups (Hindu, Muslim, Sikh & Christians) of Jammu region were also screened for UCP2 -866G/A promoter polymorphism (rs659366). The allelic odds ratio (OR) as observed for UCP2 -866G/A polymorphism in the four population groups showed significant association with Muslim & Sikh population groups. The study undertaken supports the findings of the previous investigations and thus is an addition to the existing literatute in support of UCP2 and T2DM.

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Role of Uncoupling Protein 2 in Pancreatic Cell Function: Secretion and Survival

Oxidative Stress and Inflammatory Mechanisms in Obesity, Diabetes, and the Metabolic Syndrome ◽

10.1201/9781420043792-19 ◽

2007 ◽

pp. 233-246

Keyword(s):

Cell Function ◽

Uncoupling Protein ◽

Uncoupling Protein 2 ◽

Pancreatic Cell

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The role of uncoupling protein 2 in macrophages and its impact on obesity-induced adipose tissue inflammation and insulin resistance

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.014868 ◽

2020 ◽

Vol 295 (51) ◽

pp. 17535-17548

Author(s):

Xanthe A. M. H. van Dierendonck ◽

Tiphaine Sancerni ◽

Marie-Clotilde Alves-Guerra ◽

Rinke Stienstra

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Macrophage Activation ◽

Uncoupling Protein ◽

Uncoupling Protein 2 ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Obesity And Diabetes ◽

Adipose Tissue Macrophages

The development of a chronic, low-grade inflammation originating from adipose tissue in obese subjects is widely recognized to induce insulin resistance, leading to the development of type 2 diabetes. The adipose tissue microenvironment drives specific metabolic reprogramming of adipose tissue macrophages, contributing to the induction of tissue inflammation. Uncoupling protein 2 (UCP2), a mitochondrial anion carrier, is thought to separately modulate inflammatory and metabolic processes in macrophages and is up-regulated in macrophages in the context of obesity and diabetes. Here, we investigate the role of UCP2 in macrophage activation in the context of obesity-induced adipose tissue inflammation and insulin resistance. Using a myeloid-specific knockout of UCP2 (Ucp2ΔLysM), we found that UCP2 deficiency significantly increases glycolysis and oxidative respiration, both unstimulated and after inflammatory conditions. Strikingly, fatty acid loading abolished the metabolic differences between Ucp2ΔLysM macrophages and their floxed controls. Furthermore, Ucp2ΔLysM macrophages show attenuated pro-inflammatory responses toward Toll-like receptor-2 and -4 stimulation. To test the relevance of macrophage-specific Ucp2 deletion in vivo, Ucp2ΔLysM and Ucp2fl/fl mice were rendered obese and insulin resistant through high-fat feeding. Although no differences in adipose tissue inflammation or insulin resistance was found between the two genotypes, adipose tissue macrophages isolated from diet-induced obese Ucp2ΔLysM mice showed decreased TNFα secretion after ex vivo lipopolysaccharide stimulation compared with their Ucp2fl/fl littermates. Together, these results demonstrate that although UCP2 regulates both metabolism and the inflammatory response of macrophages, its activity is not crucial in shaping macrophage activation in the adipose tissue during obesity-induced insulin resistance.

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