Background: PPARγ agonists improve insulin sensitivity but also evoke weight gain.Results: GQ-16 is a PPARγ partial agonist that blocks receptor phosphorylation by Cdk5 and improves insulin sensitivity in diabetic mice in the absence of weight gain.Conclusion: The unique binding mode of GQ-16 appears to be responsible for the compound's advantageous pharmacological profile.Significance: Similar compounds could have promise as anti-diabetic therapeutics.

This distinctive phenotype can only be explained by the combined deficiency of functionally important selenoproteins and pinpoints the clinical relevance of selenoproteins and selenium economy in human development.

Coffee consumption is associated with reduced risk of conditions that share low-grade inflammation as their physiopathological basis. We therefore summarized the effects of coffee or coffee components on serum levels of inflammatory markers. Clinical trials assessing the effect of coffee, caffeine or other coffee components on inflammatory markers were searched without restriction to publication date. Fifteen studies (8 involving coffee and 7 caffeine) were included. Increased adiponectin levels were found in four of seven trials comparing filtered coffee/caffeinated coffee with placebo or comparing its levels at baseline and after consumption of medium or dark roasted coffee, but no change was seen in caffeine trials. None of the five studies assessing the effects of coffee found changes in C-reactive protein (CPR), but one out of three trials found decreased CPR levels in response to caffeine. Interleukin (IL)-6 was increased by caffeinated coffee compared with placebo in one of four coffee trials, and by caffeine in three out of five studies. Caffeine increased IL-10 levels in two of three trials. These data suggest a predominant anti-inflammatory action of coffee but not of caffeine consumption. Moreover, the proinflammatory and anti-inflammatory responses to caffeine point to its complex effects on the inflammatory response.

Obesity is now a worldwide pandemic. The usual explanation given for the prevalence of obesity is that it results from consumption of a calorie dense diet coupled with physical inactivity. However, this model inadequately explains rising obesity in adults and in children over the past few decades, indicating that other factors must be important contributors. An Endocrine-Disrupting Chemical (EDC) is an exogenous chemical, or mixture that interferes with any aspect of hormone action. EDCs have become pervasive in our environment, allowing humans to be exposed daily through ingestion, inhalation, and direct dermal contact. Exposure to EDCs has been causally linked with obesity in model organisms and associated with obesity occurrence in humans. Obesogens are chemicals, including some EDCs that promote adipogenesis and obesity, in vivo, by a variety of mechanisms. The environmental obesogen model holds that exposure to obesogens elicits a predisposition to obesity and that such exposures may be an important yet overlooked factor in the obesity pandemic. Effects produced by EDCs and obesogen exposure may be passed to subsequent, unexposed generations. This “generational toxicology” is not currently factored into risk assessment by regulators but may be another important factor in the obesity pandemic as well as in the worldwide increases in the incidence of noncommunicable diseases that plague populations everywhere. This review addresses the current evidence on how obesogens affect body mass, discusses long-known chemicals that have been more recently identified as obesogens, and how the accumulated knowledge can help identify EDCs hazards.