Metabolism: clinical and experimental
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Pain is an integral part of the defense mechanisms required for survival. Several hereditary syndromes of complete or almost complete insensitivity to pain have been identified and include channelopathy-associated pain insensitivity, of which the most likely candidate gene is the α-subunit of the voltage-gated sodium channel known as Na(v)1.7. Five hereditary sensory and autonomic neuropathy syndromes have been described. ⋯ Most current knowledge on the genetic regulation of pain has been derived from animal models developed mainly in mice. Genomics has the potential to contribute to therapeutic advances with the promising approach of using small interfering RNA in the control of neuropathic pain. Knowledge of the genetic factors that affect opioid efficacy, metabolism, and adverse effects has the potential for personalizing both acute and chronic pain management, and for designing more useful opiate pain medications with lower adverse event profiles.
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Impaired lung function is a risk factor for cardiovascular events and mortality. In addition, lung function impairment is also associated with insulin resistance and type 2 diabetes mellitus. It is well known that a common mechanism, such as insulin resistance and obesity, underlies metabolic syndrome. ⋯ Waist girth, systolic blood pressure, and triglyceride were associated with forced vital capacity (FVC); and only triglyceride was so with forced expiratory volume in 1 second (FEV(1)), but not with FEV(1)/FVC ratio. The odds ratio of metabolic syndrome for restrictive lung disease (FVC <80%, FEV(1)/FVC >0.7) was 1.40 (95% confidence interval, 1.01-1.98), and that for obstructive lung disease (FEV(1)/FVC <0.7) was 0.93 (95% confidence interval, 0.67-1.28) after adjustment for covariates. These results indicate that low pulmonary function in the general population is associated with clustering of metabolic syndrome risk factors and, furthermore, that restrictive lung disease is also related to metabolic syndrome.
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Metabolic syndrome (MetS) as defined by the Adult Treatment Panel (ATP) III criteria includes 3 metabolic parameters: serum glucose, triglycerides, and high-density lipoprotein cholesterol (HDL-C) measurements. However, the impact of each of the 3 metabolic parameters on cardiovascular disease (CVD) risk in African American women (AAW) is unknown. Therefore, we investigated CVD risk clusters associated with each of the 3 metabolic components of MetS in adult nondiabetic, overweight/obese AAW. ⋯ We found that alterations in serum glucose and HDL-C were more predictive of MetS, each yielding approximately 40% of the prevalence of MetS in our nondiabetic, obese AAW. We found that triglycerides had the least impact on MetS in our AAW. We propose (1) that the 3 metabolic parameters for MetS defined by ATP III should be weighted differently with respect to their potential for CVD risks and perhaps outcomes and (2) that nondiabetic AAW in our third tertile of serum glucose (>100 mg/dL) and/or first tertile of HDL-C (<40 mg/dL) should be targeted for screening for MetS.
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Nonalcoholic fatty liver disease results from overconsumption and is a significant and increasing cause of liver failure. The type of diet that is conducive to the development of this disease has not been established, and evidence-based treatment options are currently lacking. We hypothesized that the onset of hepatic steatosis is linked to the consumption of a diet with a high fat content, rather than related to excess caloric intake. ⋯ Dietary fat content, independent from caloric intake, is a crucial factor in the development of hepatic steatosis, obesity, and insulin resistance in the C57BL/6J diet-induced obesity model caused by increased uptake of free fatty acids and de novo lipogenesis. In addition, once established, all these features of the metabolic syndrome can be successfully reversed after switching obese mice to a diet low in fat. Low-fat diets deserve attention in the investigation of a potential treatment of patients with nonalcoholic fatty liver disease.
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Skeletal muscle mitochondrial dysfunction is associated with aging and diabetes, which decreases respiratory capacity and increases reactive oxygen species. Lipoic acid (LA) possesses antioxidative and antidiabetic properties. Metabolic action of LA is mediated by activation of adenosine monophosphate-activated protein kinase (AMPK), a cellular energy sensor that can regulate peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), a master regulator of mitochondrial biogenesis. ⋯ We conclude that LA improves skeletal muscle energy metabolism in the aged mouse possibly through enhancing AMPK-PGC-1alpha-mediated mitochondrial biogenesis and function. Moreover, LA increases lean mass loss possibly by suppressing protein synthesis in the skeletal muscle by down-regulating the mTOR signaling pathway. Thus, LA may be a promising supplement for treatment of obesity and/or insulin resistance in older patients.