Modulation of Adipocytokines Response and Weight Loss Secondary to a Hypocaloric Diet in Obese Patients by -55CT Polymorphism of UCP3 Gene

Institute of Endocrinology and Nutrition, Medicine School and Unit of Investigation, Hospital Rio Hortega, University of Valladolid, Valladolid, Spain-RD 056/0013.
Hormone and Metabolic Research (Impact Factor: 2.12). 03/2008; 40(3):214-8. DOI: 10.1055/s-2008-1046796
Source: PubMed


Decreased expression or function of UCP3 (uncoupling protein 3) could reduce energy expenditure and increase the storage of energy as fat. Some studies have pointed to a role of UCP3 in the regulation of whole body energy homeostasis, diet induced obesity, and regulation of lipids as metabolic substrates. The C/C genotype of a polymorphism in the UCP3 promoter (-55C-->T) is associated with an increased expression of UCP3 mRNA in muscle. The aim of our study was to investigate the influence of -55CT polymorphism of UCP3 gene on adipocytokines response and weight loss secondary to a hypocaloric diet in obese patients. A population of 107 obese (body mass index >30) nondiabetic outpatients was analyzed in a prospective way. Before and after three months of a hypocaloric diet, an indirect calorimetry, tetrapolar electrical bioimpedance, blood pressure, a serial assessment of nutritional intake with 3-day written food records, and biochemical analysis were performed. The lifestyle modification program consisted of a hypocaloric diet (1520 kcal, 52% of carbohydrates, 25% of lipids and 23% of proteins). The exercise program consisted of aerobic exercise for at least 3 times per week (60 minutes each). The mean age was 49.5+/-34.5 years and the mean BMI 34.5+/-4.8, with 27 males (25.3%) and 80 females (74.7%). Ninety patients (25 males/65 females) (83.6%) had the genotype 55CC (wild group) and 17 patients (2 male/15 females) (16.4%) 55CT (mutant group). The percentage of responders (weight loss) was similar in both groups (wild group: 84.7% vs. mutant group: 81.8%). BMI, weight, fat mass, systolic blood pressure, LDL cholesterol, waist circumference, and waist-to-hip ratio decreased in the wild group and RMR and VO (2) were increased. In the mutant group, BMI and weight decreased. Leptin and IL-6 levels have a significant decrease in the wild group (9.6%: p<0.05) and (30.5%: p<0.05), respectively. Patients with -55CC genotype have a significant decrease in leptin, interleukin 6, BMI, weight, fat mass, systolic blood pressure, LDL cholesterol, waist circumference, waist-to-hip ratio weight, fat mass, and systolic blood pressure.

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    • "Interestingly, the ADRB3 Trp64Arg polymorphism may affect the regional distribution of fat loss (Nakamura et al., 2000), and could impair the capacity to lose visceral adipose tissue in response to prolonged caloric restriction (Tchernof et al., 2000). Different mutations in the uncoupling protein genes, such as UCP1 at -3826A/G position or rs1800592 (Nagai et al., 2011), UCP2 insertion/deletion (Mutombo, Yamasaki, &amp; Shiwaku, 2013;Papazoglou et al., 2012) and UCP3 -55CT (rs1800849) carriers (De Luis, Aller, Izaola, Sagrado, &amp; Conde, 2008b), may also result in differences in weight loss due to the genotype. On the other hand, other trials that investigated Trp64Arg variation (rs4994) in the ADRB3 gene (De Luis, Gonz alez Sagrado, Aller, Izaola, &amp; Conde, 2009;Sakane et al., 1997;Yamakita, Ando, Tang, &amp; Yamagata, 2010), as well as the Arg16Gly polymorphism (rs1042713) of ADRB2 gene (Sakane, Yoshida, Umekawa, Kogure, &amp; Kondo, 1999) have shown a majority of results in favor of a role in weight resistance under energy deficit but with one exception (Lee, Kawakubo, Inoue, &amp; Akabayashi, 2006). "
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