Uncoupling proteins, dietary fat and the metabolic syndrome

There has been intense interest in defining the functions of UCP2 and UCP3 during the nine years since the cloning of these UCP1 homologues. Current data suggest that both UCP2 and UCP3 proteins share some features with UCP1, such as the ability to reduce mitochondrial membrane potential, but they also have distinctly different physiological roles. Human genetic studies consistently demonstrate the effect of UCP2 alleles on type-2 diabetes. Less clear is whether UCP2 alleles influence body weight or body mass index (BMI) with many studies showing a positive effect while others do not. There is strong evidence that both UCP2 and UCP3 protect against mitochondrial oxidative damage by reducing the production of reactive oxygen species. The evidence that UCP2 protein is a negative regulator of insulin secretion by pancreatic β-cells is also strong: increased UCP2 decreases glucose stimulated insulin secretion ultimately leading to β-cell dysfunction. UCP2 is also neuroprotective, reducing oxidative stress in neurons. UCP3 may also transport fatty acids out of mitochondria thereby protecting the mitochondria from fatty acid anions or peroxides. Current data suggest that UCP2 plays a role in the metabolic syndrome through down-regulation of insulin secretion and development of type-2 diabetes. However, UCP2 may protect against atherosclerosis through reduction of oxidative stress and both UCP2 and UCP3 may protect against obesity. Thus, these UCP1 homologues may both contribute to and protect from the markers of the metabolic syndrome

Genetic variation in a member of the laminin gene family affects variation in body composition in Drosophila and humans

<p>Abstract</p> <p>Background</p> <p>The objective of the present study was to map candidate loci influencing naturally occurring variation in triacylglycerol (TAG) storage using quantitative complementation procedures in <it>Drosophila melanogaster</it>. Based on our results from <it>Drosophila</it>, we performed a human population-based association study to investigate the effect of natural variation in <it>LAMA5 </it>gene on body composition in humans.</p> <p>Results</p> <p>We identified four candidate genes that contributed to differences in TAG storage between two strains of <it>D. melanogaster</it>, including <it>Laminin A </it>(<it>LanA</it>), which is a member of the α subfamily of laminin chains. We confirmed the effects of this gene using a viable <it>LanA </it>mutant and showed that female flies homozygous for the mutation had significantly lower TAG storage, body weight, and total protein content than control flies. <it>Drosophila LanA </it>is closely related to human <it>LAMA5 </it>gene, which maps to the well-replicated obesity-linkage region on chromosome 20q13.2-q13.3. We tested for association between three common single nucleotide polymorphisms (SNPs) in the human <it>LAMA5 </it>gene and variation in body composition and lipid profile traits in a cohort of unrelated women of European American (EA) and African American (AA) descent. In both ethnic groups, we found that SNP rs659822 was associated with weight (EA: <it>P </it>= 0.008; AA: <it>P </it>= 0.05) and lean mass (EA: <it>P= </it>0.003; AA: <it>P </it>= 0.03). We also found this SNP to be associated with height (<it>P </it>= 0.01), total fat mass (<it>P </it>= 0.01), and HDL-cholesterol (<it>P </it>= 0.003) but only in EA women. Finally, significant associations of SNP rs944895 with serum TAG levels (<it>P </it>= 0.02) and HDL-cholesterol (<it>P </it>= 0.03) were observed in AA women.</p> <p>Conclusion</p> <p>Our results suggest an evolutionarily conserved role of a member of the laminin gene family in contributing to variation in weight and body composition.</p

Parent-Led Activity and Nutrition (plan) for Healthy Living: Design and Methods

Child obesity has become an important public health concern, especially in rural areas. Primary care providers are well positioned to intervene with children and their parents, but encounter many barriers to addressing child overweight and obesity. This paper describes the design and methods of a cluster-randomized controlled trial to evaluate a parent-mediated approach utilizing physician\u27s brief motivational interviewing and parent group sessions to treat child (ages 5–11 years) overweight and obesity in the primary care setting in Southern Appalachia. Specific aims of this pilot project will be 1) to establish a primary care based and parent-mediated childhood overweight intervention program in the primary care setting, 2) to explore the efficacy of this intervention in promoting healthier weight status and health behaviors of children, and 3) to examine the acceptability and feasibility of the approach among parents and primary care providers. If proven to be effective, this approach may be an exportable model to other primary care practices

The uncoupling protein 1 gene, UCP1, is expressed in mammalian islet cells and associated with acute insulin response to glucose in African American families from the IRAS Family Study

BACKGROUND: Variants of uncoupling protein genes UCP1 and UCP2 have been associated with a range of traits. We wished to evaluate contributions of known UCP1 and UCP2 variants to metabolic traits in the Insulin Resistance and Atherosclerosis (IRAS) Family Study. METHODS: We genotyped five promoter or coding single nucleotide polymorphisms (SNPs) in 239 African American (AA) participants and 583 Hispanic participants from San Antonio (SA) and San Luis Valley. Generalized estimating equations using a sandwich estimator of the variance and exchangeable correlation to account for familial correlation were computed for the test of genotypic association, and dominant, additive and recessive models. Tests were adjusted for age, gender and BMI (glucose homeostasis and lipid traits), or age and gender (obesity traits), and empirical P-values estimated using a gene dropping approach. RESULTS: UCP1 A-3826G was associated with AIR(g )in AA (P = 0.006) and approached significance in Hispanic families (P = 0.054); and with HDL-C levels in SA families (P = 0.0004). Although UCP1 expression is reported to be restricted to adipose tissue, RT-PCR indicated that UCP1 is expressed in human pancreas and MIN-6 cells, and immunohistochemistry demonstrated co-localization of UCP1 protein with insulin in human islets. UCP2 A55V was associated with waist circumference (P = 0.045) in AA, and BMI in SA (P = 0.018); and UCP2 G-866A with waist-to-hip ratio in AA (P = 0.016). CONCLUSION: This study suggests a functional variant of UCP1 contributes to the variance of AIR(g )in an AA population; the plausibility of this unexpected association is supported by the novel finding that UCP1 is expressed in islets

Effect of high-intensity interval training in adolescents with asthma: The eXercise for Asthma with Commando Joe's® (X4ACJ) trial

BackgroundHigher levels of cardiorespiratory fitness are associated with reduced asthma severity and increased quality of life in those with asthma. Therefore, the purpose of this study was to evaluate the effectiveness of a 6-month high-intensity interval training (HIIT) intervention in adolescents with and without asthma.MethodsA total of 616 adolescents (334 boys; 13.0 ± 1.1 years; 1.57 ± 0.10m; 52.6 ± 12.9kg, mean ± SD), including 155 with asthma (78 boys), were recruited as part of a randomized control trial from 5 schools (4 control, 1 intervention). The 221 intervention participants (116 boys; 47 asthma) completed 6 months of school-based HIIT (30mins, 3 times per week, 10–30s bouts at >90% age-predicted maximum heart rate with equal rest). At baseline, mid-intervention, post-intervention and 3-month follow-up, measurements for 20-metre shuttle run, body mass index (BMI), lung function, Pediatric Quality of Life Inventory, Paediatric Asthma Quality of Life Questionnaire and Asthma Control Questionnaire were collected. Additionally, 69 adolescents (21 boys; 36 asthma) also completed an incremental ramp test. For analysis, each group's data (intervention and control) was divided into those with and without asthma.ResultsParticipants with asthma did not differ from their peers in any parameter of aerobic fitness, at any time-point, but were characterised by a greater BMI. The intervention elicited a significant improvement in maximal aerobic fitness but no change in sub-maximal parameters of aerobic fitness, lung function or quality of life, irrespective of asthma status. Those in the intervention group maintained their BMI, whereas BMI significantly increased in the control group throughout the 6-month period.ConclusionsHIIT represents an effective tool for improving aerobic fitness and maintaining BMI in adolescents, irrespective of asthma status. HIIT was well tolerated by those with asthma, who evidenced a similar aerobic fitness to their healthy peers and responded equally well to a HIIT programme

Dietary factors are not associated with high levels of obesity in New Zealand Pacific preschool children.

Pacific children living in New Zealand (NZ) are prone to excessive weight gain. In this study, we assessed the anthropometric status of 2- to 5-y-old Pacific children (n = 60) in relation to their macronutrient intakes. Measurements of height (n = 56), weight (n = 60), midarm circumference, and triceps skinfold thickness (n = 58), and 2-d weighed food records (n = 60) and demographic data were collected. Z-score results (mean +/- SD) showed that these children were tall (0.61 +/- 1.1) and heavy (1.67 +/- 1.1) for their age, and had high arm-muscle-area-for-height (geometric mean, 2.05). Over 64 and 45% of children were classified as overweight (including obesity) and obese, respectively. The percentage of energy contributed by fat in their diets met recommendations. In contrast, the percentage of energy contributed by sugar was high. The macronutrient intakes of children classified as obese (n = 32) compared with non-obese (n = 24) did not differ; however, their adjusted energy intakes were higher [5.79 (1.4) vs. 4.97 (1.4) MJ/d; P = 0.01]. Overweight and obesity were very common among very young NZ Pacific children, although the dietary etiology was not elucidated. These results emphasize the urgent need for obesity prevention for NZ Pacific children that begins early in life to avoid a future public health crisis