Background: The C/C genotype of a polymorphism in the uncoupling protein3 (UCP3) promoter (-55C->T) (rs1800849) is associated with an increased body mass index. Objective: The aim of our study was to investigate the effect of polymorphism on the UCP3 promoter (-55C->T) on insulin resistance and cardiovascular risk factors secondary to a high protein/low carbohydrate vs. a standard hypocaloric diets (1,000 kcal/day). Design: A population of 283 obese subjects was analyzed in a randomized trial. A nutritional evaluation was performed at the beginning and at the end of a 9-month period in which subjects received 1 of 2 diets (diet HP: high protein/low carbohydrate vs. diet S: standard diet). Results: Weight improvement was higher in non-T carriers. With both diets and only in wild genotype (diet HP vs. diet S), total cholesterol (-9.7 ± 4.0 vs. -11.1 ± 2.0 mg/dl; p > 0.05) and low density lipoprotein (LDL) cholesterol (-8.3 ± 3.0 vs. -5.5 ± 2.7 mg/dl; p > 0.05) decreased. The improvement in these parameters was similar in subjects with diet HP than HS. With diet HP and only in wild genotype, glucose (-5.2 ± 2.2 mg/dl; p < 0.05), triglycerides (-15.5 ± 3.9 mg/dl; p < 0.05), insulin levels (-3.9 ± 3.1 UI/l; p < 0.05) and homeostasis model assessment (HOMA-R; -0.6 ± 0.1 units; p < 0.05) decreased. Conclusion: Carriers of T allele have a different response than non-carrier subjects, with a lack of decrease of LDL cholesterol, glucose, insulin levels and HOMA-R. The weight loss was lower in T carriers. HP diet showed a better metabolic response than S diet in 55CC homozygous.

1.
Tuomilehto J, Lindstrom J, Eriksson JG: Finnish Diabetes Prevention Study Group: prevention of type 2 diabetes mellitus changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:1343-1350.
2.
Matsuzawa Y: Adipocytokines: emerging therapeutic targets. Curr Atheroscler Rep 2005;7:58-62.
3.
Hu T, Mills KT, Yao L, et al: Effects of low-carbohydrate diets versus low-fat diets on metabolic risk factors: a meta-analysis of randomized controlled clinical trials. Am J Epidemiol 2012;176(suppl 7):S44-S54.
4.
Castañeda-González LM, Bacardí Gascón M, Jiménez Cruz A: Effects of low carbohydrate diets on weight and glycemic control among type 2 diabetes individuals: a systemic review of RCT greater than 12 weeks. Nutr Hosp 2011;26:1270-1276.
5.
Nordmann AJ, Nordmann A, Briel M, et al: Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials. Arch Intern Med 2006;166:285-293.
6.
Bueno NB, de Melo IS, de Oliveira SL, et al: Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. Br J Nutr 2013;110:1178-1187.
7.
Nordmann AJ, Suter-Zimmermann K, Bucher HC, et al: Meta-analysis comparing Mediterranean to low-fat diets for modification of cardiovascular risk factors. Am J Med 2011;124:841-851.
8.
Vidal-Puig A, Solanes G, Grujic D, Flier JS, Lowell BB: UCP3: an uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue. Biochem Biophys Res Commun 1997;235:79-82.
9.
Kopecký J, Rossmeisl M, Flachs P, Bardová K, Brauner P: Mitochondrial uncoupling and lipid metabolism in adipocytes. Biochem Soc Trans 2001;29:791-797.
10.
Otabe S, Clement K, Dina C, Pelloux V, Guy-Grand B, Froguel P, Vasseur F: A genetic variation in the 5' flanking region of the UCP3 gene is associated with body mass index in humans in interaction with physical activity. Diabetologia 2000;43:245-249.
11.
De Luis DA, Aller R, Izaola O, Sagrado MG, Conde R: Modulation of adipocytokines response and weight loss secondary to a hypocaloric diet in obese patients by -55CT polymorphism of UCP3 gene. Horm Metab Res 2008;40:214-218.
12.
Luis DA, Aller R, Izaola O, Gonzalez Sagrado M, Conde R. Modulation of insulin concentrations and metabolic parameters in obese patients by -55CT polymorphism of the UCP3 gene secondary to two hypocaloric diets. Horm Metab Res 2009;41:62-66.
13.
De Luis DA, Aller R, Izaola O, De La Fuente B, Conde R, Eiros Bouza JM: Relation of -55CT polymorphism of UCP3 gene with weight loss and metabolic changes after a high monounsaturated fat diet in obese non diabetic patients. Eur Rev Med Pharmacol Sci 2013;17:2810-2815.
14.
De Luis Da, Aller R, Izaola O, GonzÁlez Sagrado M, Conde R, Ruiz Mambrilla M: [Relation of -55CT polymorphism of UCP3 gene with weight loss and metabolic changes after a high polyunsaturated fat diet in obese patients]. Nutr Hosp 2012;27:1190-1195.
15.
Mataix J, Mañas M: Tablas de Composición de Alimentos Españoles. Ed, University of Granada, 2003.
16.
Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
17.
Duart Duart MJ, Arroyo CO, Moreno Frígols JL: Validation of a kinetic model for the reactions in RIA. Clin Chem Lab Med 2002;40:1161-1167.
18.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-419.
19.
Lehmann HP, Block D, Markert-Hahn C, Zolg JW: New concepts in systemic autoimmunity testing. Scand J Clin Lab Invest Suppl 2001;235:84-90.
20.
Lukaski H, Johnson PE, Bolonchuk WW, Lykken GI: Assessment of fat-free mass using bioelectrical impedance measurements of the human body. Am J Clin Nutr 1985;41:810-817.
21.
Hesselink MK, Mensink M, Schrauwen P: Human uncoupling protein-3 and obesity: an update. Obes Res 2003;11:1429-1443.
22.
Millet L, Vidal H, Andreelli F, et al: Increased uncoupling protein-2 and -3 mRNA expression during fasting in obese and lean humans. J Clin Invest 1997;100:2665-2670.
23.
Dalgaard LT, Sørensen TI, Drivsholm T, Borch-Johnsen K, Andersen T, Hansen T, Pedersen O: A prevalent polymorphism in the promoter of the UCP3 gene and its relationship to body mass index and long term body weight change in the Danish population. J Clin Endocrinol Metab 2001;86:1398-1402.
24.
Meirhaeghe A, Amouyel P, Helbecque N, et al: An uncoupling protein 3 gene polymorphism associated with a lower risk of developing Type II diabetes and with atherogenic lipid profile in a French cohort. Diabetologia 2000;43:1424-1428.
25.
Alonso A, Martí A, Corbalán MS, Martínez-González MA, Forga L, Martínez JA: Association of UCP3 gene -55C>T polymorphism and obesity in a Spanish population. Ann Nutr Metab 2005;49:183-188.
26.
Liu YJ, Liu PY, Long J, Lu Y, Elze L, Recker RR, Deng HW: Linkage and association analyses of the UCP3 gene with obesity phenotypes in Caucasian families. Physiol Genomics 2005;22:197-203.
27.
Brondani L, Assmann T, de Souza B, Bouças A, Canani LH, Crispim D: Meta-analysis reveals the association of common variants in the uncoupling protein (UCP) 1-3 genes with body mass index variability. PLoS One 2014;9:e96411.
28.
Lapice E, Monticelli A, Cocozza S, Pinelli M, Giacco A, Rivellese AA, Cocozza S, Riccardi G, Vaccaro O: The energy intake modulates the association of the -55CT polymorphism of UCP3 with body weight in type 2 diabetic patients. Int J Obes (Lond) 2014;38:873-877.
29.
De Luis DA, Pacheco D, Aller R, González Sagrado M, Izaola O, Terroba MC, Cuellar L, Conde R, Martin T, Perez Castrillon JL: Influence of -55CT polymorphism of UCP3 gene on surgical results of biliopancreatic diversion. Obes Surg 2010;20:895-899.
30.
Santos FL, Esteves SS, da Costa Pereira A, et al: Systematic review and meta-analysis of clinical trials of the effects of low carbohydrate diets on cardiovascular risk factors. Obes Rev 2012;13:1048-1066.
31.
Kodama S, Saito K, Tanaka S, et al: Influence of fat and carbohydrate proportions on the metabolic profile in patients with type 2 diabetes: a meta-analysis. Diabetes Care 2009;32:959-965.
32.
Ochoa MC, Santos JL, Azcona C, Moreno-Aliaga MJ, Martínez-González MA, Martínez JA, Marti A; GENOI Members: Association between obesity and insulin resistance with UCP2-UCP3 gene variants in Spanish children and adolescents. Mol Genet Metab 2007;92:351-358.
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