Contrasting individuals who smoke only a few cigarettes per day, or “”chippers”", to heavy smoking,

nicotine dependent subjects, focuses a genetic study on the transition from smoking to nicotine dependence. This approach has identified distinct genetic buy INCB018424 variants that contribute to nicotine dependence on chromosome 15 in the region of the alpha 5-alpha 3-beta 4 family of nicotinic receptor genes.

This region of association includes an amino acid change in the alpha 5 nicotinic receptor protein, which is most likely a biological variant altering the risk of developing dependence. There is also evidence that other variants alter alpha 5 nicotinic receptor gene expression and potentially the risk of smoking. The discovery of these genetic variants and their contribution to the development of nicotine dependence highlight some of the many challenges in genetic studies. The first is that the prevalence of risk alleles can vary across Populations so that a genetic risk factor can have a larger or small effect in a population

depending on its frequency. The second challenge is that the risk that each SNS-032 molecular weight genetic variant contributes in the development of a disorder is small and so it is many genes along with environmental risk factors that contribute to the development of a disorder. Interestingly, recent genetic studies of lung cancer and chronic obstructive pulmonary disease demonstrate that this same region has an important

genetic influence on these disorders. Finally, there are differences in the risk of developing nicotine dependence based on gender and socioeconomic status. As our understanding of the genetic contributions BI 2536 inhibitor of nicotine dependence increases, we may improve and personalize our treatments for smoking cessation and enhance our knowledge of other smoking related diseases in those who are at high risk for the many adverse consequences of smoking. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“In recent years, AMP-activated protein kinase (AMPK) has emerged as a potential target for physiological and pharmacologic treatment of several metabolic disorders. AMPK is a heterotrimeric enzyme that has been proposed to function as a ‘fuel gauge’ that monitors changes in the energy status of cells. One pathway that is central to the integrated effects of AMPK in peripheral tissues is the stimulation of fatty acid oxidation and prevention of intracellular lipid accumulation, which could exert an important antilipotoxic effect and be of great relevance for the treatment of obesity and Type 2 diabetes. Here, we review the recent advances in the physiological role of AMPK in the regulation of lipid metabolism in peripheral tissues, and the molecular mechanisms involved in these processes.