Mustelin L, Pietiläinen KH, Rissanen A, Sovijärvi AR, Piirilä P, Naukkarinen J, Peltonen L, Kaprio J, Yki-Järvinen H. Acquired obesity and poor physical fitness impair expression of genes of mitochondrial oxidative phosphorylation in monozygotic twins discordant for obesity. Am J Physiol Endocrinol Metab 295: E148 -E154, 2008. First published May 6, 2008; doi:10.1152/ajpendo.00580.2007.-Defects in expression of genes of oxidative phosphorylation in mitochondria have been suggested to be a key pathophysiological feature in familial insulin resistance. We examined whether such defects can arise from lifestyle-related factors alone. Fourteen obesity-discordant (BMI difference 5.2 Ϯ 1.8 kg/m 2 ) and 10 concordant (1.0 Ϯ 0.7 kg/m 2 ) monozygotic (MZ) twin pairs aged 24 -27 yr were identified among 658 MZ pairs in the population-based FinnTwin16 study. Whole body insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp technique. Transcript profiles of mitochondrial genes were compared using microarray data of fat biopsies from discordant twins. Body composition of twins was determined using DEXA and maximal oxygen uptake (V O2max) and working capacity (Wmax) using a bicycle ergometer exercise test with gas exchange analysis. The obese cotwins had lower insulin sensitivity than their nonobese counterparts (M value 6.1 Ϯ 2.0 vs. 9.2 Ϯ 3.2 mg ⅐ kg LBM Ϫ1 ⅐ min Ϫ1 , P Ͻ 0.01). Transcript levels of genes involved in the oxidative phosphorylation pathway (GO:0006119) in adipose tissue were lower (P Ͻ 0.05) in the obese compared with the nonobese cotwins. The obese cotwins were also less fit, as measured by V O2max (50.6 Ϯ 6.5 vs. 54.2 Ϯ 6.4 ml ⅐ kg LBM Ϫ1 ⅐ min Ϫ1 , for obese vs. nonobese, P Ͻ 0.05), Wmax (3.9 Ϯ 0.5 vs. 4.4 Ϯ 0.7 W/kg LBM, P Ͻ 0.01) and also less active, by the Baecke leisure time physical activity index (2.8 Ϯ 0.5 vs. 3.3 Ϯ 0.6, P Ͻ 0.01). This implies that acquired poor physical fitness is associated with defective expression of the oxidative pathway components in adipose tissue mitochondria. body composition; cardiorespiratory fitness; spiroergometry; gene expression OBESITY IS ASSOCIATED WITH poor physical fitness (15) and insulin resistance (31, 32). Recent studies have suggested that genetic factors account for a substantial fraction (estimates of 50 -90%) of the population variance in BMI (39, 65), insulin action (23-52%) (16,27,35,46,60) and physical activity (32-79%) (24,41,70). These results raise the possibility that shared genetic influences underlie the association between obesity, insulin resistance, and fitness. Recently, it has been suggested that mitochondrial dysfunction might be a key factor in development of insulin resistance (37). Several studies have reported type 2 diabetic patients and "prediabetic" insulinresistant subjects to have impaired structure and function of mitochondria (28,48,53,54,66) and decreased expression of genes encoding key enzymes in oxidative metabolism and mitochondrial function (47, 52). Petersen et al. (54) reported reduced mitochondrial ...

Exhaled nitric oxide (NO) is a marker of eosinophilic inflammation of the airway mucosa accompanying changes in the clinical condition of asthma. Allergen exposure has been associated with delayed elevation of exhaled NO. The aim of this study was to assess the asthmatic airway inflammation with exhaled NO measurements during specific bronchial challenge tests with occupational agents.Forty patients with suspected occupational asthma were investigated. Specific bronchial challenge tests were performed with forced expiratory volume in one second or peak expiratory flow follow-up, supplemented by exhaled NO measurements before and 24 h after challenge tests.In active challenges, which induced bronchoconstriction, a significant mean increase of exhaled NO concentration was noted. In patients with a normal or slightly increased (v14.5 parts per billion (ppb)) basal NO level and a late bronchoconstriction, a significant increase in exhaled NO was seen. Patients with a high basal NO level (w14.5 ppb) and a significant bronchoconstriction did not show a significant NO elevation. Challenge tests without bronchoconstriction were not associated with a significant elevation of exhaled NO.Exhaled nitric oxide measurements can be used to indicate the development of airway inflammation accompanying late asthmatic reaction after bronchial challenge tests in patients with a normal or slightly increased basal nitric oxide concentration.

Exercise training prevents age‐related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late‐life exercise mitigates epigenetic aging in rodent muscle. Whether exercise training can decelerate, or reverse epigenetic aging in humans is unknown. Here, we performed a powerful meta‐analysis of the methylome and transcriptome of an unprecedented number of human skeletal muscle samples (n = 3176). We show that: (1) individuals with higher baseline aerobic fitness have younger epigenetic and transcriptomic profiles, (2) exercise training leads to significant shifts of epigenetic and transcriptomic patterns toward a younger profile, and (3) muscle disuse “ages” the transcriptome. Higher fitness levels were associated with attenuated differential methylation and transcription during aging. Furthermore, both epigenetic and transcriptomic profiles shifted toward a younger state after exercise training interventions, while the transcriptome shifted toward an older state after forced muscle disuse. We demonstrate that exercise training targets many of the age‐related transcripts and DNA methylation loci to maintain younger methylome and transcriptome profiles, specifically in genes related to muscle structure, metabolism, and mitochondrial function. Our comprehensive analysis will inform future studies aiming to identify the best combination of therapeutics and exercise regimes to optimize longevity.

In lung sound research, low-frequency noise usually disturbs the sound signal being recorded. Some researchers therefore use high-pass filtration before the final analysis. In this study, the effect of digital and analog high-pass filtration on the morphology of the lung sound crackles is evaluated. The original nonprefiltered crackle waveform is presented, and the effect of the high-pass filtration on the crackle waveform characteristics is elucidated in one patient with silicoasbestosis.