Objective: Obesity and type 2 diabetes (T2D) are reaching epidemic proportions in Western societies, and they contribute to substantial morbidity and mortality. The peroxisome proliferator-activated receptor g (PPARg) and PPARg coactivator-1a (PGC-1a) system plays an important role in the regulation of efficient energy utilization and oxidative phosphorylation, both of which are decreased in obesity and insulin resistance. Design and methods: We measured the metabolic parameters and the expression of PPARg and PGC-1a mRNA using quantitative real-time PCR in omental and subcutaneous (SC) adipose tissues in an observational study of 153 individuals as well as in SC fat and skeletal muscle in an interventional study of 60 subjects (20 each with normal glucose tolerance, impaired glucose tolerance, and T2D) before and after intensive physical training for 4 weeks. Results: PPARg and PGC-1a mRNA expression in both fat depots as well as in skeletal muscle is associated with markers of insulin resistance and cardiovascular risk. PGC-1a mRNA expression is significantly higher in SC fat than in omental fat, whereas PPARg mRNA expression is not significantly different between these fat depots. Skeletal muscle and SC fat PPARg and PGC-1a mRNA expression increased significantly in response to physical training. Conclusions: Gene expression of PPARg and PGC-1a in human adipose tissue is related to markers of insulin resistance and cardiovascular risk. Increased muscle and adipose tissue PPARg and PGC-1a expression in response to physical training may mediate the beneficial effects of exercise on insulin sensitivity.

ObjectiveHuman bone morphogenetic protein receptor 2 (BMPR2) is essential for BMP signalling and may be involved in the regulation of adipogenesis. The BMPR2 locus has been suggested as target of recent selection in human populations. We hypothesized that BMPR2 might have a role in the pathophysiology of obesity.Research Design and MethodsEvolutionary analyses (dN/dS, Fst, iHS) were conducted in vertebrates and human populations. BMPR2 mRNA expression was measured in 190 paired samples of visceral and subcutaneous adipose tissue. The gene was sequenced in 48 DNA samples. Nine representative single nucleotide polymorphisms (SNPs) were genotyped for subsequent association studies on quantitative traits related to obesity in 1830 German Caucasians. An independent cohort of 925 Sorbs was used for replication. Finally, relation of genotypes to mRNA in fat was examined.ResultsThe evolutionary analyses indicated signatures of selection on the BMPR2 locus. BMPR2 mRNA expression was significantly increased both in visceral and subcutaneous adipose tissue of 37 overweight (BMI>25 and <30 kg/m2) and 80 obese (BMI>30 kg/m2) compared with 44 lean subjects (BMI<25 kg/m2) (P<0.001). In a case-control study including lean and obese subjects, two intronic SNPs (rs6717924, rs13426118) were associated with obesity (adjusted P<0.05). Combined analyses including the initial cohort and the Sorbs confirmed a consistent effect for rs6717924 (combined P = 0.01) on obesity. Moreover, rs6717924 was associated with higher BMPR2 mRNA expression in visceral adipose tissue.ConclusionCombined BMPR2 genotype-phenotype-mRNA expression data as well as evolutionary aspects suggest a role of BMPR2 in the pathophysiology of obesity.

Inhibition of fatty acid synthase (FASN) induces a rapid decline in fat stores in mice, suggesting a role for this enzyme in energy homeostasis. To investigate the potential role of FASN in the pathophysiology of human obesity, the FASN gene was sequenced in 48 German whites. Thirty‐five single‐nucleotide polymorphisms (SNPs) were identified. Eight SNPs representative for their linkage disequilibrium groups and the Val1483Ile (rs2228305) substitution were genotyped for subsequent association analyses in 1,311 adults from Germany. Further, the tagging SNPs were genotyped also in German childhood cohorts (738 schoolchildren, 205 obese children). Effects of genetic variation on FASN mRNA expression in visceral and subcutaneous adipose tissue from a subgroup of 172 subjects were analyzed. Several polymorphisms in the FASN (rs62078748, rs2229422, rs2229425, and rs17848939) were nominally associated with obesity in case–control studies including 446 obese subjects (BMI ≥30 kg/m2) and 389 lean controls (BMI ≤25 kg/m2) (adjusted P < 0.05). The strongest significant effect was found for rs2229422 (P = 1.3 × 10−5 adjusted for age, sex, type 2 diabetes status), which was supported by associations with BMI, waist‐to‐hip ratio (WHR), fasting plasma insulin and glucose infusion rate (adjusted P < 0.05). Subjects with the Val1483Ile substitution appeared to be protected against obesity. In addition, rs17848939 was nominally significantly associated with the ratio of visceral/subcutaneous FASN mRNA expression (adjusted P = 0.04). No effect of genetic variation in FASN on obesity was found in children. In conclusion, our data indicate a role of FASN genetic variation in susceptibility to obesity in adults.

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Internal carotid artery (ICA) injury following transsphenoidal surgery is a rare but potentially fatal complication. Usually, endovascular occlusion of the ICA or stent graft placement is the treatment of these vascular complications described in literature. We present a case of ICA perforation during transsphenoidal surgery in a patient with limited collateral cerebral blood flow and with ectasia of the ICA that rule out an endovascular treatment. We report the surgical revascularization via high-flow extra-intracranial radial artery bypass and consicutive artery ligation.