Uncoupling protein-1 (UCP-1) has been suggested as an obesity gene in humans. It is expressed exclusively in the inner mitochondrial membrane of brown adipose tissue and acts by uncoupling substrate oxidation from ATP generation reducing metabolic efficiency [1]. Brown adipose tissue plays an important part in the regulation of energy expenditure in rodents as animals with BAT dysfunction develop obesity [2]. Its function in humans is, however, less clear.A naturally occurring variant in UCP-1 that results in an A®G base pair substitution in the promoter region (±3826) is observed with a frequency of 0.27 in Caucasians [3]. The ±3826 G variant of UCP-1 has been weakly associated with increased weight gain over time in morbidly obese women [4] and resistance to weight loss during moderate energy restriction [5] although it has not been independently associated with a reduced basal metabolic rate [6]. Furthermore, the ±3826 G variant has not been associated with BMI in the general population and the distribution of this variant is even between lean and obese subjects [4,7]. This suggests that the ±3826 G polymorphism of UCP-1 does not have a large role in obesity. Because the ±3826 G variant has, however, been linked to weight gain in obese women, we hypothesise that it will be related to higher BMI in an already overweight cohort. Diabetologia (2000) ) for the ±3826 A®G uncoupling protein-1 polymorphism. Of the 526 women genotyped 144 had fasting blood samples analysed for glucose and lipid measurements. Results. The ±3826 G allele was found with a frequency of 0.23 and was associated with higher BMI (p = 0.02). A higher frequency of this polymorphism (0.33) was found in subjects with Type II (non-insulin-dependent) diabetes mellitus (p = 0.02), though adjustment for BMI weakened this significance (p = 0.06). The ±3826 G variant was associated with increased fasting glucose (p = 0.01). This was, however, a result of a greater proportion of women with Type II diabetes also having the G variant (p = 0.10, adjusted for Type II diabetes). The ±3826 G variant of uncoupling protein-1 did not have an effect on other metabolic variables associated with obesity. Conclusion/interpretation. In overweight Australian women the ±3826 G variant of UCP-1 increased the susceptibility to obesity indicating that UCP-1 could be involved in weight regulation. [Diabetologia (2000) 43: 242±244]

S104Heart, Lung and Circulation CSANZ 2012 Abstracts 2012;21:S1-S142 epidemic. The impact of the aging population on the effects of obesity on the atria is not known. Methods: Intracellular membrane potential recordings were obtained from the isolated right atria of Zucker lean (n = 12) and obese rats (n = 12) aged 3, 7 and 12 months respectively (n = 4 per age group). An aluminosilicate glass electrode (100 M , filled with 3 M KCl) was used to record intracellular action potential parameters during atrial pacing. Atrial orientation and pacing site and glass electrode position were kept consistent throughout each experiment.Results: Obese animals were significantly heavier than age-matched lean animals across all age groups (p < 0.01). Blood pressure was significantly higher in obese animals aged >7 months (p < 0.0001) compared to lean animals, and further increased with age (p < 0.05). In lean animals, APD demonstrated a gradual decrease and plateau with age alone. In contrast, in obese animals there was a progressive increase in APD (p < 0.05). At each pacing cycle length (200, 300 and 400 ms), the APD was significantly longer in obese rats aged 7 and 10 months compared to their age-matched lean rats (p < 0.001).Conclusion: The impact of obesity on the substrate for AF is greater with increasing age. These findings have significant implications to the consequences of the obesity epidemic in an aging population. http://dx.

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