Genetic variation and obesity in Australian women: A prospective study.

Objective: A number of candidate genes have been implicated in the pathogenesis of obesity in humans. This study examines associations between longitudinal changes in body mass and composition and the presence of polymorphisms in the ß-3 adrenergic receptor, tumor necrosis factor-α, leptin, and leptin receptor (Lepr) in a cohort of Australian women.

Research Methods and Procedures: Healthy white Australian women (n = 335) were randomly selected from the Barwon region of Victoria and underwent baseline anthropometry and double-energy X-ray absorptiometry for assessment of body mass and adiposity. These measurements were repeated again at 2-year follow-up. Genomic DNA was extracted and used for polymerase chain reaction-based genotyping of all polymorphisms.

Results: The Pro1019Pro Lepr polymorphism was associated with longitudinal increases in body weight (p = 0.02), fat mass (p = 0.05), and body mass index (p = 0.01) in this study, and individuals homozygous for the A allele at this locus had a greater propensity to gain body fat over time. The largest effects on body composition seemed to be in individuals already obese at baseline. Changes in body weight, fat mass, percent body fat, and body mass index over a 2-year period were not associated with genetic variation in the ß-3 adrenergic receptor (Trp64Arg), tumor necrosis factor-α promoter, or leptin genes in non-obese or obese women.

Discussion: These results suggest that a Lepr polymorphism is involved in the regulation of body mass and adiposity in obese Australian white women, which may have implications for the treatment of obesity in this population.

Coronary angiography observations: evidence-based or ritualistic practice?

Objective: The purposes of this study were to describe the incidence and occurrence of femoral artery bleeding during the first 6 hours after coronary angiography and to determine whether there is a relationship between  current postangiogram observation protocols and the detection of  complications.

Design: This was a prospective descriptive study.

Setting: The study was conducted in 3 university hospitals in Melbourne, Australia.

Patients: Subjects included 55 patients representing the complication rate of 1075 patients, mean age 61 years (SD, 12), 69% male.

Results: About 5.1% of patients had 1 or more incidents of bleeding  requiring manual compression. In 4.2% of patients, bleeding occurred within 6 hours of angiography. Bleeding occurred a median of 2.02 hours (Q1 = 45 minutes, Q3 = 4.31 hours) after angiography. Patients without pressure bandaging bled a median of 1.32 hours (Q1 = 36.50 minutes, Q3 = 2.59 hours) after angiography. Patients with pressure bandaging bled a median of 4.75 hours (Q1 = 2.25 hours, Q3 = 7.28 hours) after angiography. In 40.6% of cases, bleeding was detected through the patient’s call for assistance, and in 59.4% of cases nurses noted bleeding while checking the puncture site. Postcatheter observations were recorded 23.70 (SD, 14.60) minutes before the bleeding incident. There were no significant changes in vital signs, systolic blood pressure (P > .05), diastolic blood pressure (P > .05), or pulse (P > .05) before or during a bleeding episode. All were within normal parameters. No neurovascular assessment anomalies were detected.

Conclusion: The use of pressure bandaging has a significant effect on the incidence and pattern of bleeding. Routine vital sign measurement has no relevance in detecting local complications after angiography. The most significant complication is bleeding that requires manual compression. Detection is through frequent puncture site observation and patient recognition and communication.

Fasting activates the gene expression of UCP3 independent of genes necessary for lipid transport and oxidation in skeletal muscle

Fasting triggers a complex array of adaptive metabolic and hormonal responses including an augmentation in the capacity for mitochondrial fatty acid (FA) oxidation in skeletal muscle. This study hypothesized that this adaptive response is mediated by increased mRNA of key genes central to the regulation of fat oxidation in human skeletal muscle. Fasting dramatically increased UCP3 gene expression, by 5-fold at 15 h and 10-fold at 40 h. However the expression of key genes responsible for the uptake, transport, oxidation, and re-esterification of FA remained unchanged following 15 and 40 h of fasting. Likewise there was no change in the mRNA abundance of transcription factors. This suggests a unique role for UCP3 in the regulation of FA homeostasis during fasting as adaptation to 40 h of fasting does not require alterations in the expression of other genes necessary for lipid metabolism.

Exercise training increases lipid metabolism gene expression in human skeletal muscle

The effects of a single bout of exercise and exercise training on the expression of genes necessary for the transport and beta -oxidation of fatty acids (FA), together with the gene expression of transcription factors implicated in the regulation of FA homeostasis were investigated. Seven human subjects (3 male, 4 female, 28.9 ± 3.1 yr of age, range 20-42 yr, body mass index 22.6 kg/m², range 17-26 kg/m²) underwent a 9-day exercise training program of 60 min cycling per day at 63% peak oxygen uptake (V_{O2 peak}; 104 ± 14 W). On days 1 and 9 of the program, muscle biopsies were sampled from the vastus lateralis muscle at rest, at the completion of exercise, and again 3 h postexercise. Gene expression of key components of FA transport [FA translocase (FAT/CD36), plasma membrane-associated FA-binding protein], beta -oxidation [carntine palmitoyltransferase(CPT) I, beta -hydroxyacyl-CoA dehydrogenase] and transcriptional control [peroxisome proliferator-activated receptor (PPAR)alpha , PPARgamma , PPARgamma coactivator 1, sterol regulatory element-binding protein-1c] were unaltered by exercise when measured at the completion and at 3 h postexercise. Training increased total lipid oxidation by 24% (P < 0.05) for the 1-h cycling bout. This increased capacity for lipid oxidation was accompanied by an increased expression of FAT/CD36 and CPT I mRNA. Similarly, FAT/CD36 protein abundance was also upregulated by exercise training. We conclude that enhanced fat oxidation after exercise training is most closely associated with the genes involved in regulating FA uptake across the plasma membrane (FAT/CD36) and across the mitochondrial membrane (CPT I).