Distinct gene signatures predict insulin resistance in young mice with high fat diet-induced obesity.

Highly inbred C57BL/6 mice show wide variation in their degree of insulin resistance in response to diet-induced obesity even though they are almost genetically identical. Here we employed transcriptional profiling by RNA sequencing (RNA-Seq) of visceral adipose tissue (VAT) and liver in young mice to determine how gene expression patterns correlate with the later development of high-fat diet (HFD)-induced insulin resistance in adulthood. To accomplish this goal, we partially removed and banked tissues from pubertal mice.

Dual actions of a novel bifunctional compound to lower glucose in mice with diet-induced insulin resistance.

Docosahexaenoic acid (DHA 22:6n-3) and salicylate are both known to exert anti-inflammatory effects. This study investigated the effects of a novel bifunctional drug compound consisting of DHA and salicylate linked together by a small molecule that is stable in plasma but hydrolyzed in the cytoplasm. The components of the bifunctional compound acted synergistically to reduce inflammation mediated via nuclear factor κB in cultured macrophages.

Pancreatic beta-cell failure in obese mice with human-like CMP-Neu5Ac hydroxylase deficiency.

Type 2 diabetes is highly prevalent in human populations, particularly in obese individuals, and is characterized by progressive pancreatic β-cell dysfunction and insulin resistance. Most mammals, including Old World primates, express two major kinds of sialic acids, N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), typically found at the distal ends of glycoconjugate chains at the cell surface. Humans are uniquely unable to produce endogenous Neu5Gc due to an inactivating mutation in the CMP-Neu5Ac hydroxylase (CMAH) gene.