studies can be very powerful in detecting the effect of a gene on a disease if that effect is not too weak; however, because their validation relies on replication studies, at the same time, they bear the intrinsic limitation of being exposed to the effect of allelic and multilocus heterogeneity which, as we know, underly many inherited diseases. During the preparation of this manuscript, other studies 8-10 reported a lack of association between HOXA1 (A218G) and autism.

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Aim: Data on the skeletal muscle characteristics of patients and animals with lifestyle-related diseases are limited. We investigated mRNA expression levels and fiber profiles in the skeletal muscles of rats with obesity, diabetes, hypertension, and/or hyperlipidemia. Methods: The mRNA expression levels of peroxisome proliferator-activated receptors (PPAR and PPAR / ), PPAR coactivator-1 (PGC-1 ), stearoyl-CoA desaturase-1 (SCD-1), carnitine palmitoyl-transferase (CPT ), medium-chain acyl-CoA dehydrogenase (MCAD), and mitochondrial transcriptional factor A (TFAM) in the soleus muscles were compared among 15-week-old control (WR), type 2 diabetic (GK), hypertensive (SHR), and hyperlipidemic (CP) rats. The fiber profiles in the soleus muscles of these rats were also determined. Results: GK rats showed lower PPAR / , PGC-1 , and MCAD expression levels than WR rats. SHR rats showed higher PPAR and MCAD and lower PPAR / expression levels than WR rats. CP rats showed lower PPAR / and higher SCD-1 expression levels than WR rats. The muscles of WR, SHR, and CP rats had low-oxidative type and high-oxidative type A and type C fibers, whereas the muscle of GK rats had only low-oxidative type fibers. Conclusions:The skeletal muscles of rats with lifestyle-related diseases have unique mRNA expression patterns and fiber profiles depending on the type of disease. For example, the lower PGC-1 and MCAD mRNA expression levels in the soleus muscles of type 2 diabetic rats are associated with the presence of only low-oxidative type fibers in the muscle. J Atheroscler Thromb, 2009; 16:576-585.Key words; Lifestyle-related disease, mRNA expression level, Muscle fiber type bility of ATPase at acidic pH. Type A fibers become ATPase negative at a faster rate than type B fibers when the acidity of the preincubation medium increases. Type C fibers have been identified in skeletal muscles, particularly in the soleus muscle of rats; these fibers are ATPase positive, irrespective of the pH of the preincubation medium. Glycolytic enzyme activity is higher in type A, type B, and type C fibers than in type fibers, whereas oxidative enzyme activity is higher in type , type A, and type C fibers than in type B fibers; therefore, the presence of different types of fibers correlates with the metabolic properties of individual skeletal muscles. Skeletal muscles exhibit plasticity and undergo fiber type transitions under various conditions, such as growth, aging,

The effects of hyperbaric exposure with high oxygen concentration on glucose and insulin levels and skeletal muscle-fiber properties were investigated in type 2 diabetic Goto-Kakizaki rats. Five-week-old rats were exposed to a hyperbaric environment (1.25 atmospheric pressure) with a high oxygen concentration (36%) for 6 h daily. Glucose and insulin levels and properties including fiber-type distribution, cross-sectional area, and oxidative enzyme activity in the soleus muscle were examined after hyperbaric exposure for 4 weeks. The growth-related increase in glucose level was inhibited by hyperbaric exposure, and insulin also showed lower levels compared with control rats. The percentage of low-oxidative type I fibers in the muscle decreased and high-oxidative type IIA and type IIC fibers, which were not detected in the muscle of control rats, were observed after hyperbaric exposure. The oxidative enzyme activity of type I fibers in the muscle increased after hyperbaric exposure. Hyperbaric exposure with high oxygen concentration might therefore provide a new approach to improve the glucose tolerance, insulin resistance, and altered skeletal muscle metabolism that are caused by diabetes mellitus. Muscle Nerve, 2006.

Titanium dioxide nanoparticles (TiO NPs) constitute the top five NPs in use today. In this study, oral administration of 50, 100, and 200 mg/kg body weight (b.w.) TiO NPs increases plasma glucose in mice, whereas 10 and 20 mg/kg b.w. TiO NPs did not. RNA sequencing (RNA-seq) technology was used to investigate genome-wide effects of TiO NPs. Clustering analysis of the RNA-seq data showed the most significantly enriched gene ontology terms and KEGG pathways related to the endoplasmic reticulum (ER) and ER stress. Molecular biology verification showed that 50 mg/kg b.w. and higher doses TiO NPs activated a xenobiotic biodegradation response and increased expression of cytochrome P450 family genes in mouse livers, thus inducing ER stress in mice. ER stress-activated MAPK and NF-κB pathways and induced an inflammation response, resulting in phosphorylation of the insulin receptor substrate 1 and, consequently, insulin resistance. This was the main mechanism by which TiO NPs increased plasma glucose in mice. Meanwhile, ER stress disturbed the monooxygenase system, and thus generated reactive oxygen species (ROS). Relief of ER stress with 4-phenylbutyric acid inhibited all the above effects of TiO NPs, including the generation of ROS. Therefore, TiO NP-induced ER stress was a decisive factor with a central role in plasma glucose disturbance in mice.

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