Glo1 reduction in mice results in age- and sex-dependent metabolic dysfunction.

Objectives: Advanced glycation end products (AGEs) have been implicated as an important mediator of metabolic disorders including obesity, insulin resistance, and coronary artery disease. Glyoxalase 1 (Glo1) is a critical enzyme in the clearance of toxic dicarbonyl such as methylglyoxal, precursors of AGEs. The role of AGE-independent mechanisms that underly Glo1-induced metabolic disorders have yet to be elucidated.

Ketogenic diet therapy for pediatric epilepsy is associated with alterations in the human gut microbiome that confer seizure resistance in mice.

The gut microbiome modulates seizure susceptibility and the anti-seizure effects of the ketogenic diet (KD) in animal models, but whether these relationships translate to KD therapies for human epilepsy is unclear. We find that the clinical KD alters gut microbial function in children with refractory epilepsy. Colonizing mice with KD-associated microbes promotes seizure resistance relative to matched pre-treatment controls.

Shared and distinct pathways and networks genetically linked to coronary artery disease between human and mouse.

Mouse models have been used extensively to study human coronary artery disease (CAD) or atherosclerosis and to test therapeutic targets. However, whether mouse and human share similar genetic factors and pathogenic mechanisms of atherosclerosis has not been thoroughly investigated in a data-driven manner. We conducted a cross-species comparison study to better understand atherosclerosis pathogenesis between species by leveraging multiomics data.

Role of Matrix Gla Protein in Transforming Growth Factor-β Signaling and Nonalcoholic Steatohepatitis in Mice.

Background & Aims: Nonalcoholic steatohepatitis (NASH) is a complex disease involving both genetic and environmental factors in its onset and progression. We analyzed NASH phenotypes in a genetically diverse cohort of mice, the Hybrid Mouse Diversity Panel, to identify genes contributing to disease susceptibility.

Methods: A "systems genetics" approach, involving integration of genetic, transcriptomic, and phenotypic data, was used to identify candidate genes and pathways in a mouse model of NASH.