Conclusions
These studies identify LXRα as a key mediator of the long-term metabolic alterations induced by preconception paternal alcohol use.
Methods
Male offspring of alcohol-exposed sires were challenged with a high-fat diet and the molecular pathways controlling glucose and lipid homeostasis assayed for LXR-induced alterations.
Results
Similar to findings in studies employing LXR agonists we found that the male offspring of alcohol-exposed sires display resistance to diet-induced obesity and improved glucose homeostasis when challenged with a high-fat diet. This improved metabolic adaptation is mediated by LXRα trans-repression of inflammatory cytokines, releasing IKKβ inhibition of the insulin signaling pathway. Interestingly, paternally programmed increases in LXRα expression are liver-specific and do not manifest in the pancreas or visceral fat. Conclusions: These studies identify LXRα as a key mediator of the long-term metabolic alterations induced by preconception paternal alcohol use.