Genetic Variance in<i>Uncoupling Protein 2</i>in Relation to Obesity, Type 2 Diabetes, and Related Metabolic Traits: Focus on the Functional −866G&gt;A Promoter Variant (rs659366)

Dalgaard, Louise Torp

doi:10.1155/2011/340241

Cited by 50 publications

(52 citation statements)

References 112 publications

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“…PBMC gene expression level of UCP2 in ARO subjects was significantly decreased compared with both normal weight and MHO subjects. UCP2 has previously been associated with obesity (Dalgaard 2011;Dalgaard and Pedersen 2001). UCP2 is important for uncoupling respiration and promotes mitochondrial fatty acid oxidation (Fisler and Warden 2006), although the physiological significance of its uncoupling activity is discussed (Pecqueur et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Altered expression of genes involved in lipid metabolism in obese subjects with unfavourable phenotype

et al. 2013

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Obesity (BMI C30 kg/m 2 ) increases the risk of developing lifestyle-related diseases. A subgroup of obese individuals has been described as ''metabolically healthy, but obese'' (MHO). In contrast to at-risk obese (ARO), the MHO phenotype is defined by a favourable lipid profile and a normal or only slightly affected insulin sensitivity, despite the same amount of body fat. The objective was to characterize the metabolic phenotype of MHO subjects. We screened a variety of genes involved in lipid metabolism and inflammation in peripheral blood mononuclear cells (PBMC). Obese subjects (men and women; 18-70 years) with BMI C30 kg/m 2 were characterized as MHO (n = 9) or as ARO (n = 10). In addition, eleven healthy, normal weight subjects characterized as healthy by the same criteria as described for the MHO subjects were included. We found that with similar weight, total fat mass and fat mass distribution, the ARO subjects have increased plasma levels of gamma-glutamyl transpeptidase and free fatty acids. This group also has altered expression levels of a number of genes linked to lipid metabolism in PBMC with reduced gene expression levels of uncoupling protein 2, hormone-sensitive lipase and peroxisome proliferatoractivated receptor d compared with MHO subjects. The present metabolic differences between subgroups of obese subjects may contribute to explain some of the underlying mechanisms causing the increased risk of disease among ARO subjects compared with MHO subjects.

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Section: Discussionmentioning

confidence: 99%

Altered expression of genes involved in lipid metabolism in obese subjects with unfavourable phenotype

et al. 2013

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“…Moreover, upregulation of UCP2, which has been detected in type 2 diabetes mellitus, may be linked to the proteosome system dysfunction [63,307]. Physiological role and regulation of UCP3 and UCP2, which is particularly highly expressed in the pancreatic b-cells in type 2 diabetes mellitus, have been discussed in the several recent reviews [308][309][310][311].…”

Section: Ucp Activity and Its Regulationmentioning

confidence: 99%

Mitochondrial oxidative metabolism and uncoupling proteins in the failing heart

2014

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Despite significant progress in cardiovascular medicine, myocardial ischemia and infarction, progressing eventually to the final end point heart failure (HF), remain the leading cause of morbidity and mortality in the USA. HF is a complex syndrome that results from any structural or functional impairment in ventricular filling or blood ejection. Ultimately, the heart's inability to supply the body's tissues with enough blood may lead to death. Mechanistically, the hallmarks of the failing heart include abnormal energy metabolism, increased production of reactive oxygen species (ROS) and defects in excitation-contraction coupling. HF is a highly dynamic pathological process, and observed alterations in cardiac metabolism and function depend on the disease progression. In the early stages, cardiac remodeling characterized by normal or slightly increased fatty acid (FA) oxidation plays a compensatory, cardioprotective role. However, upon progression of HF, FA oxidation and mitochondrial oxidative activity are decreased, resulting in a significant drop in cardiac ATP levels. In HF, as a compensatory response to decreased oxidative metabolism, glucose uptake and glycolysis are upregulated, but this upregulation is not sufficient to compensate for a drop in ATP production. Elevated mitochondrial ROS generation and ROS-mediated damage, when they overwhelm the cellular antioxidant defense system, induce heart injury and contribute to the progression of HF. Mitochondrial uncoupling proteins (UCPs), which promote proton leak across the inner mitochondrial membrane, have emerged as essential regulators of mitochondrial membrane potential, respiratory activity and ROS generation. Although the physiological role of UCP2 and UCP3, expressed in the heart, has not been clearly established, increasing evidence suggests that these proteins by promoting mild uncoupling could reduce mitochondrial ROS generation and cardiomyocyte apoptosis and ameliorate thereby myocardial function. Further investigation on the alterations in cardiac UCP activity and regulation will advance our understanding of their physiological roles in the healthy and diseased heart and also may facilitate the development of novel and more efficient therapies.

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“…The structure of UCP2, determined by NMR in 2011, closely resembles the bovine ADP/ATP carrier (Berardi et al, 2011). The physiological functions of UCP2 are still under debate (Dalgaard, 2011). A number of studies have reported that it can mediate proton leak, which can uncouple respiration and ATP synthesis, leading to energy consumed in the form of heat.…”

Section: Introductionmentioning

confidence: 99%

Lack of association of functional UCP2 -866G/A and Ala55Val polymorphisms and type 2 diabetes in the Chinese population based on a case-control study and a meta-analysis

Qin¹,

Wen²,

Qu³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Uncoupling protein 2 (UCP2) is a mitochondrial transporter protein and can affect the function of β-cells. We investigated a possible association between functional UCP2 -866G/ A and Ala55Val polymorphisms and type 2 diabetes in 715 Hubei Han Chinese. No significant association was found, either for the -866G/A polymorphism (allele, P = 0.254; genotype, P = 0.508) or for the Ala55Val polymorphism (allele, P = 0.250; genotype, P = 0.896). Then, we reviewed the association of UCP2 -866G/A and Ala55Val polymorphisms with type 2 diabetes susceptibility in the Chinese population with a meta-analysis. Our meta-analysis, which included 3643 Chinese, further confirmed a lack of association of -866G/A and Ala55Val with type 2 diabetes (additive model: -866G/A, odds ratio = 1.09, 95% confidence interval = 0.94-1.27, P = 0.25; Ala55Val, odds ratio = 1.21, 95% confidence interval = 0.85-1.72, P = 0.28). 3325©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 12 (3): 3324-3334 (2013) UCP2 -866G/A and Ala55Val polymorphisms and type 2 diabetes Based on our case-control study and meta-analysis, we conclude that UCP2 Ala55Val and -866G/A polymorphisms are not significantly associated with type 2 diabetes risk in the Chinese population.

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Genetic Variance inUncoupling Protein 2in Relation to Obesity, Type 2 Diabetes, and Related Metabolic Traits: Focus on the Functional −866G>A Promoter Variant (rs659366)

Cited by 50 publications

References 112 publications

Altered expression of genes involved in lipid metabolism in obese subjects with unfavourable phenotype

Altered expression of genes involved in lipid metabolism in obese subjects with unfavourable phenotype

Mitochondrial oxidative metabolism and uncoupling proteins in the failing heart

Lack of association of functional UCP2 -866G/A and Ala55Val polymorphisms and type 2 diabetes in the Chinese population based on a case-control study and a meta-analysis

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