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The TaqIA RFLP is associated with attenuated intervention-induced body weight loss and increased carbohydrate intake in post-menopausal obese women.

ABSTRACT: INTRODUCTION:Polymorphisms of the dopamine receptor D2 (DRD2) gene have been associated with obesity phenotypes. Our aim was to examine if the genotype of TaqIA Restriction Fragment Length Polymorphism (RFPL) was related to an attenuated weight loss response or to changes in energy expenditure (EE) and food preference before and after weight loss. methods: Obese post-menopausal women (age=57.1 ± 4.6 yr, weight=85.4 ± 15.4 kg and BMI=32.8 ± 4.5 kg/m(2)) were genotyped for TaqIA (n=127) by using PCR-RFLP analysis and categorized as possessing at least one copy of the A1 allele (A1(+)) or no copy (A1(-)). Women were randomized into two groups, caloric restriction (CR) and caloric restriction+resistance training (CRRT) and in this study were further classified as follows: A1(+)CR, A1(+)CRRT, A1-(-)CR and (-)A1(-)CRRT. Body composition, total daily EE, physical activity EE, Resting EE (REE), and energy intake were obtained at baseline and post-intervention using DXA, doubly-labeled water, indirect calorimetry, and 3-day dietary records, respectively. RESULTS:Overall, all of the anthropometric variables and REE significantly decreased post-intervention (p<0.001). Women in the CRRT group lost significantly more fat mass (FM) than the CR women (p<0.05). There were significant time by group by allele interactions for attenuated body weight (BW), BMI, and FM loss for A1(+) (vs. A1(-)) in CRRT (p<0.05) and for increased % carbohydrate intake (p<0.01). CONCLUSION:TaqIA genotype was associated with body weight loss post-intervention; more specifically, carriers of the A1 allele lost significantly less BW and FM than the A1(-) and had increased carbohydrate intake in the CRRT group.

SUBMITTER: Cameron JD

PROVIDER: S-EPMC3934842 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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The TaqIA RFLP is associated with attenuated intervention-induced body weight loss and increased carbohydrate intake in post-menopausal obese women.

Cameron Jameason D JD Riou Marie-Ève MÈ Tesson Frédérique F Goldfield Gary S GS Rabasa-Lhoret Rémi R Brochu Martin M Doucet Éric É

Appetite 20120929 1

<h4>Introduction</h4>Polymorphisms of the dopamine receptor D2 (DRD2) gene have been associated with obesity phenotypes. Our aim was to examine if the genotype of TaqIA Restriction Fragment Length Polymorphism (RFPL) was related to an attenuated weight loss response or to changes in energy expenditure (EE) and food preference before and after weight loss. methods: Obese post-menopausal women (age=57.1 ± 4.6 yr, weight=85.4 ± 15.4 kg and BMI=32.8 ± 4.5 kg/m(2)) were genotyped for TaqIA (n=127) by ...[more]

PMID: 23032305

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Project description:Background/objectivesCholecystokinin (CCK) is a regulator of appetite and energy intake in man. The aim of this study was to determine the effect of NN9056, a long-acting CCK-1 receptor-selective CCK analogue, on food intake and body weight (BW) in obese Göttingen Minipigs.Subjects/methodsTolerability of NN9056 and acute effects on food intake, pancreas histology, amylase and lipase levels were assessed in lean domestic pigs in doses up to 100 nmol/kg (n = 3-4). Subsequently, obese Göttingen Minipigs were treated subcutaneously (s.c.) once daily for 13 weeks with vehicle, NN9056 low dose (regulated from 5 to 2 nmol/kg) or NN9056 high dose (10 nmol/kg) (n = 7-8). Food intake was measured daily and BW twice weekly. At the end of the treatment period, an intravenous glucose tolerance test (IVGTT) and a 24-h exposure profile was obtained. Data are mean ± SD.ResultsThe acute studies in domestic pigs showed significant and dose-dependent effect of NN9056 on food intake, acceptable tolerability and no histopathological signs of pancreatitis. Sub-chronic treatment in obese Göttingen Minipigs was also well tolerated and accumulated food intake was significantly lower in both treated groups compared to vehicle, with no significant difference between the dose levels of NN9056 (41.8 ± 12.6, 51.5 ± 13.8 and 86.5 ± 19.5 kg in high-dose, low-dose and vehicle groups, respectively, p = 0.012 and p < 0.0001 for low and high dose vs. vehicle, respectively). Accordingly, there was a weight loss in both treated groups vs. a weight gain in the vehicle group (-7.2 ± 4.6%, -2.3 ± 3.2% and 12.3 ± 3.9% in the high-dose, low-dose and vehicle groups, respectively, p < 0.0001 for both vs. vehicle). IVGTT data were not significantly different between groups.ConclusionNN9056, a long-acting CCK-1 receptor-selective CCK analogue, significantly reduced food intake and BW in obese Göttingen Minipigs after once daily s.c. dosing for 13 weeks.

Project description:ObjectiveAdministration of FGF21 and FGF21 analogues reduce body weight; improve insulin sensitivity and dyslipidemia in animal models of obesity and in short term clinical trials. However potential adverse effects identified in mice have raised concerns for the development of FGF21 therapeutics. Therefore, this study was designed to address the actions of FGF21 on body weight, glucose and lipid metabolism and importantly its effects on bone mineral density (BMD), bone markers, and plasma cortisol in high-fat fed obese rhesus macaque monkeys.MethodsObese non-diabetic rhesus macaque monkeys (five males and five ovariectomized (OVX) females) were maintained on a high-fat diet and treated for 12 weeks with escalating doses of FGF21. Food intake was assessed daily and body weight weekly. Bone mineral content (BMC) and BMD were measured by DEXA scanning prior to the study and on several occasions throughout the treatment period as well as during washout. Plasma glucose, glucose tolerance, insulin, lipids, cortisol, and bone markers were likewise measured throughout the study.ResultsOn average, FGF21 decreased body weight by 17.6 ± 1.6% after 12 weeks of treatment. No significant effect on food intake was observed. No change in BMC or BMD was observed, while a 2-fold increase in CTX-1, a marker of bone resorption, was seen. Overall glucose tolerance was improved with a small but significant decrease in HbA1C. Furthermore, FGF21 reduced concentrations of plasma triglycerides and very low density lipoprotein cholesterol. No adverse changes in clinical chemistry markers were demonstrated, and no alterations in plasma cortisol were observed during the study.ConclusionIn conclusion, FGF21 reduced body weight in obese rhesus macaque monkeys without reducing food intake. Furthermore, FGF21 had beneficial effects on body composition, insulin sensitivity, and plasma triglycerides. No adverse effects on bone density or plasma cortisol were observed after 12 weeks of treatment.

Dataset Information

The TaqIA RFLP is associated with attenuated intervention-induced body weight loss and increased carbohydrate intake in post-menopausal obese women.

Publications

The TaqIA RFLP is associated with attenuated intervention-induced body weight loss and increased carbohydrate intake in post-menopausal obese women.

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