Associations of Haplotypes Upstream of IRS1 with Insulin Resistance, Type 2 Diabetes, Dyslipidemia, Preclinical Atherosclerosis, and Skeletal Muscle LOC646736 mRNA Levels.

The genomic region ~500 kb upstream of IRS1 has been implicated in insulin resistance, type 2 diabetes, adverse lipid profile, and cardiovascular risk. To gain further insight into this chromosomal region, we typed four SNPs in a cross-sectional cohort and subjects with type 2 diabetes recruited from the same geographic region. From 16 possible haplotypes, 6 haplotypes with frequencies >0.

Heme oxygenase-1 drives metaflammation and insulin resistance in mouse and man.

Obesity and diabetes affect more than half a billion individuals worldwide. Interestingly, the two conditions do not always coincide and the molecular determinants of "healthy" versus "unhealthy" obesity remain ill-defined. Chronic metabolic inflammation (metaflammation) is believed to be pivotal.

Potential role of upstream stimulatory factor 1 gene variant in familial combined hyperlipidemia and related disorders.

Objective: Genetic studies implicated upstream stimulatory factor 1 (USF1) in familial combined hyperlipidemia because the rs2073658 minor allele was associated with reduced risk of familial combined hyperlipidemia and related disorders. The molecular mechanisms whereby rs2073658 influences trait expression have remained elusive.

Methods And Results: Plasma lipids, rs2073658 genotypes (N=372), and hepatic transcript levels (N=96) of USF1 and genes involved in hepatic lipoprotein production were determined in obese subjects.

Cross-talk between interferon-γ and hedgehog signaling regulates adipogenesis.

Objective: T cells and level of the cytokine interferon-γ (IFN-γ) are increased in adipose tissue in obesity. Hedgehog (Hh) signaling has been shown to potently inhibit white adipocyte differentiation. In light of recent findings in neurons that IFN-γ and Hh signaling cross-talk, we examined their potential interaction in the context of adipogenesis.