Modulation of adipocytokines response and weight loss secondary to a hypocaloric diet in obese patients by-55CT polymorphism of UCP3 gene
ABSTRACT 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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ABSTRACT: Background and objectives: The alteration in the protein expression of UCP3 could reduce energy consumption and increase energy storage as fat. The aim of our study was to investigate the influence of -55CT polymorphism of UCP3 gene in the metabolic response, weight loss and serum levels of adipokines following a hypocaloric diet rich in polyunsaturated fat in obese patients. Design: A sample of 133 obese patients were analyzed prospectively for 3 months. The hypocaloric diet was 1459 kcal, 45.7% carbohydrate, 34.4% from 19.9% lipids and proteins. The fat distribution was, a 21.8% saturated fat, 55.5% monounsaturated and 22.7% of polyunsaturated fat (7 g per day of fatty acids w6, 2 g per day of w -3 and a ratio w6/w3 of 3.5). Results: A total of 100 patients (28 males/72 females) (75.2%) had genotype - 55CC (wild genotype group) and 33 patients (8 males/25 females) (24.8%) -55CT genotype (group mutant genotype). In the wild genotype, body mass index (-2.5 ± 5.3 kg/m2), weight (-4.2 ± 3.7 kg), fat mass (-3,7 ± 3.3 kg), waist circumference (-4.1 ± 2.9 cm), systolic blood pressure (-4.9 ± 10.1 mmHg), total cholesterol levels (- 16.1 ± 23.6 mg / dl), LDL cholesterol (-11.1 ± 26.8 mg/dl), triglycerides (-12.0 ± 46.8 mg/dl), insulin (-1.8 ± 4.5 IU/L), HOMA-R (-0.6 ± 1.5) and leptin (-6.2 ± 8.4 ng/ml) decreased. In the mutant genotype anthropome-tric parameters were significantly decreased without significant changes in biochemical parameters. Conclusion: The T allele carriers of -55CT UCP3 polymorphism exhibit no metabolic response to weight loss induced by a hypocaloric diet rich in polyunsaturated fatty acids.Nutricion hospitalaria: organo oficial de la Sociedad Espanola de Nutricion Parenteral y Enteral 08/2012; 27(4):190-1195. · 1.25 Impact Factor
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ABSTRACT: Liver fat deposition related to systemic insulin resistance defines non-alcoholic fatty liver disease (NAFLD) which, when associated with oxidative hepatocellular damage, inflammation, and activation of fibrogenesis, i.e. non-alcoholic steatohepatitis (NASH), can progress towards cirrhosis and hepatocellular carcinoma. Due to the epidemic of obesity, NAFLD is now the most frequent liver disease and the leading cause of altered liver enzymes in Western countries. Epidemiological, familial, and twin studies provide evidence for an element of heritability of NAFLD. Genetic modifiers of disease severity and progression have been identified through genome-wide association studies. These include the Patatin-like phosholipase domain-containing 3 (PNPLA3) gene variant I148M as a major determinant of inter-individual and ethnicity-related differences in hepatic fat content independent of insulin resistance and serum lipid concentration. Association studies confirm that the I148M polymorphism is also a strong modifier of NASH and progressive hepatic injury. Furthermore, a few large multicentre case-control studies have demonstrated a role for genetic variants implicated in insulin signalling, oxidative stress, and fibrogenesis in the progression of NAFLD towards fibrosing NASH, and confirm that hepatocellular fat accumulation and insulin resistance are key operative mechanisms closely involved in the progression of liver damage. It is now important to explore the molecular mechanisms underlying these associations between gene variants and progressive liver disease, and to evaluate their impact on the response to available therapies. It is hoped that this knowledge will offer further insights into pathogenesis, suggest novel therapeutic targets, and could help guide physicians towards individualised therapy that improves clinical outcome.Current pharmaceutical design 02/2013; 19(29). DOI:10.2174/13816128113199990381 · 3.29 Impact Factor
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ABSTRACT: The molecular mechanism underlying adipogenesis and the physiological functions of adipose tissue are not fully understood. We describe here a unique mouse model of severe lipodystrophy. Ablation of Ptpn11/Shp2 in adipocytes, mediated by aP2-Cre, led to premature death, lack of white fat, low blood pressure, compensatory erythrocytosis, and hepatic steatosis in Shp2(fat-/-) mice. Fat transplantation partially rescued the lifespan and blood pressure in Shp2(fat-/-) mice, and administration of leptin also restored partially the blood pressure of mutant animals with endogenous leptin deficiency. Consistently, homozygous deletion of Shp2 inhibited adipocyte differentiation from embryonic stem (ES) cells. Biochemical analyses suggest a Shp2-TAO2-p38-p300-PPARγ pathway in adipogenesis, in which Shp2 suppresses p38 activation, leading to stabilization of p300 and enhanced PPARγ expression. Inhibition of p38 restored adipocyte differentiation from Shp2(-/-) ES cells, and p38 signaling is also suppressed in obese patients and obese animals. These results illustrate an essential role of adipose tissue in mammalian survival and physiology and also suggest a common signaling mechanism involved in adipogenesis and obesity development.Proceedings of the National Academy of Sciences 12/2012; 110(1). DOI:10.1073/pnas.1213000110 · 9.81 Impact Factor