Relation of −55CT polymorphism of uncoupling protein 3 gene with fat mass and insulin resistance in morbidly obese patients

Luis, Daniel Antonio de; Aller, R.; Jáuregui, Olatz Izaola; Sagrado, M. González; Conde-Vicente, Rosa; Salvador, Beatriz de la Fuente; Bobillo, Enrique Romero

doi:10.1016/j.metabol.2009.09.004

Cited by 7 publications

(5 citation statements)

References 22 publications

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“…In addition to the above adipokines, adiponectin, an adipose‐tissue‐derived hormone, plays an important role in the regulation of lipid metabolism and insulin sensitivity and also possesses anti‐inflammatory effects 44–46 being considered as an antiatherogenic adipokine 45 . In sera from KO mice, the reduced adiponectin levels are in line with alteration in fatty acids and glucose metabolism, previously reported for these mice 6–9 and with data obtained in human 47 . The changes in PAI‐1 and TIMP‐1 levels (that are known to be oppositely regulated by adiponectin 48 and that are involved in the formation, progression, and stabilization of atherosclerotic plaques, 49,50 associated with reduced adiponectin levels might support occurrence or atherogenesis.…”

Section: Discussionsupporting

confidence: 66%

“…45 In sera from KO mice, the reduced adiponectin levels are in line with alteration in fatty acids and glucose metabolism, previously reported for these mice [6][7][8][9] and with data obtained in human. 47 The changes in PAI-1 and TIMP-1 levels (that are known to be oppositely regulated by adiponectin 48 and that are involved in the formation, progression, and stabilization of atherosclerotic plaques, 49,50 associated with reduced adiponectin levels might support occurrence or atherogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Ablation of uncoupling protein 3 affects interrelated factors leading to lipolysis and insulin resistance in visceral white adipose tissue

et al. 2022

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The physiological role played by uncoupling protein 3 (UCP3) in white adipose tissue (WAT) has not been elucidated so far. In the present study, we evaluated the impact of the absence of the whole body UCP3 on WAT physiology in terms of ability to store triglycerides, oxidative capacity, response to insulin, inflammation, and adipokine production. Wild type (WT) and UCP3 Knockout (KO) mice housed at thermoneutrality (30°C) have been used as the animal model. Visceral gonadic WAT (gWAT) from KO mice showed an impaired capacity to store triglycerides (TG) as indicated by its lowered weight, reduced adipocyte diameter, and higher glycerol release (index of lipolysis). The absence of UCP3 reduces the maximal oxidative capacity of gWAT, increases mitochondrial free radicals, and activates ER stress. These processes are associated with increased levels of monocyte chemoattractant protein‐1 and TNF‐α. The response of gWAT to in vivo insulin administration, revealed by (ser473)‐AKT phosphorylation, was blunted in KO mice, with a putative role played by eif2a, JNK, and inflammation. Variations in adipokine levels in the absence of UCP3 were observed, including reduced adiponectin levels both in gWAT and serum. As a whole, these data indicate an important role of UCP3 in regulating the metabolic functionality of gWAT, with its absence leading to metabolic derangement. The obtained results help to clarify some aspects of the association between metabolic disorders and low UCP3 levels.

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Ablation of uncoupling protein 3 affects interrelated factors leading to lipolysis and insulin resistance in visceral white adipose tissue

et al. 2022

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“…The UCP3 -55C/T promoter variant is of interest because of its position at 4 bp downstream of a peroxisome proliferator-activated receptor (PPAR) responsive region, which could modify PPAR-dependent responsiveness [ 66 ]. Thus, many studies have linked this polymorphism to the regulation of lipid metabolism and insulin sensitivity [ 67 , 68 ]. Previous meta-analyses also showed that the UCP3-55C/T polymorphism is related to prominent increase in BMI, as well as risk for T2DM in Asians [ 18 , 19 , 59 ].…”

Section: Discussionmentioning

confidence: 99%

Ethnicity Differences in the Association of UCP1-3826A/G, UCP2-866G/A and Ala55Val, and UCP3-55C/T Polymorphisms with Type 2 Diabetes Mellitus Susceptibility: An Updated Meta-Analysis

Huang

Cai

Zhou

et al. 2021

BioMed Research International

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Background. The relationship between uncoupling protein (UCP) 1-3 polymorphisms and susceptibility to type 2 diabetes mellitus (T2DM) has been extensively studied, while conclusions remain contradictory. Thus, we performed this meta-analysis to elucidate whether the UCP1-3826A/G, UCP2-866G/A, Ala55Val, and UCP3-55C/T polymorphisms are associated with T2DM. Methods. Eligible studies were searched from PubMed, Cochrane Library, and Web of Science database before 12 July 2020. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Heterogeneity analysis, subgroup analysis, sensitivity analysis, and publication bias were also performed. Results. A total of 38 case-control studies were included in this meta-analysis. The overall results revealed significant association between T2DM and the UCP2 Ala55Val polymorphism (recessive model: OR = 1.25 , 95% CI 1.12-1.40, P < 0.01 ; homozygous model: OR = 1.33 , 95% CI 1.03-1.72, P = 0.029 , respectively). In subgroup analysis stratified by ethnicity, T2DM risk was increased with the UCP2 Ala55Val polymorphism (allele model: OR = 1.17 , 95% CI 1.02-1.34, P = 0.023 ; recessive model: OR = 1.28 , 95% CI 1.13-1.45, P < 0.01 ; homozygous model: OR = 1.39 , 95% CI 1.05-1.86, P = 0.023 , respectively), while decreased with the UCP2-866G/A polymorphism in Asians (dominant model: OR = 0.86 , 95% CI 0.74-1.00, P = 0.045 ). Conclusions. Our results demonstrate that the UCP2-866G/A polymorphism is protective against T2DM, while the UCP2 Ala55Val polymorphism is susceptible to T2DM in Asians.

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“…MAFLD is a polygenic disease, and the influence of gene regulation on fat oxidation metabolism is also an important factor that promotes FAO process imbalance in the development of MAFLD. For example, the nonsynonymous mutation of SOD2-C47T can reduce the activity of MnSOD and inhibit the clearance of peroxidation byproducts produced in the process of OXPHOS [108]; the mutation of UCP3-55T leads to abnormal lipolysis, causing fat accumulation and inducing inflammation [109]; GCL downregulates GCL, the rate-limiting enzyme for glutathione (GSH) synthesis, and inhibits the clearance of cellular peroxidation, resulting in the accumulation of ROS [110].…”

Section: Fatty Acid Oxidation (Fao)mentioning

confidence: 99%

Mitochondrial Dysfunction in Metabolic Dysfunction Fatty Liver Disease (MAFLD)

Zhao,

Zhou,

Wang

et al. 2023

IJMS

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Nonalcoholic fatty liver disease (NAFLD) has become an increasingly common disease in Western countries and has become the major cause of liver cirrhosis or hepatocellular carcinoma (HCC) in addition to viral hepatitis in recent decades. Furthermore, studies have shown that NAFLD is inextricably linked to the development of extrahepatic diseases. However, there is currently no effective treatment to cure NAFLD. In addition, in 2020, NAFLD was renamed metabolic dysfunction fatty liver disease (MAFLD) to show that its pathogenesis is closely related to metabolic disorders. Recent studies have reported that the development of MAFLD is inextricably associated with mitochondrial dysfunction in hepatocytes and hepatic stellate cells (HSCs). Simultaneously, mitochondrial stress caused by structural and functional disorders stimulates the occurrence and accumulation of fat and lipo-toxicity in hepatocytes and HSCs. In addition, the interaction between mitochondrial dysfunction and the liver–gut axis has also become a new point during the development of MAFLD. In this review, we summarize the effects of several potential treatment strategies for MAFLD, including antioxidants, reagents, and intestinal microorganisms and metabolites.

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Relation of −55CT polymorphism of uncoupling protein 3 gene with fat mass and insulin resistance in morbidly obese patients

Cited by 7 publications

References 22 publications

Ablation of uncoupling protein 3 affects interrelated factors leading to lipolysis and insulin resistance in visceral white adipose tissue

Ablation of uncoupling protein 3 affects interrelated factors leading to lipolysis and insulin resistance in visceral white adipose tissue

Ethnicity Differences in the Association of UCP1-3826A/G, UCP2-866G/A and Ala55Val, and UCP3-55C/T Polymorphisms with Type 2 Diabetes Mellitus Susceptibility: An Updated Meta-Analysis

Mitochondrial Dysfunction in Metabolic Dysfunction Fatty Liver Disease (MAFLD)

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