Inter- and Transgenerational Effects of Paternal Exposure to Inorganic Arsenic.

The rise of metabolic disorders in modern times is mainly attributed to the environment. However, heritable effects of environmental chemicals on mammalian offsprings' metabolic health are unclear. Inorganic arsenic (iAs) is the top chemical on the Agency for Toxic Substances and Disease Registry priority list of hazardous substances.

Coagulopathy in Malnourished Mice Is Sexually Dimorphic and Regulated by Nutrient-Sensing Nuclear Receptors.

Liver dysfunction, including coagulopathy, is a prominent feature of protein-energy malnutrition. To identify mechanisms underlying malnutrition-associated coagulopathy, we administered a low-protein low-fat diet to lactating dams and examined hepatic transcription and plasma coagulation parameters in young adult weanlings. Malnutrition impacted body composition to a greater extent in male versus female mice.

Serum Metabolomic Profiling Identifies Key Metabolic Signatures Associated With Pathogenesis of Alcoholic Liver Disease in Humans.

Alcoholic liver disease (ALD) develops in a subset of heavy drinkers (HDs). The goals of our study were to (1) characterize the global serum metabolomic changes in well-characterized cohorts of controls (Cs), HDs, and those with alcoholic cirrhosis (AC); (2) identify metabolomic signatures as potential diagnostic markers, and (3) determine the trajectory of serum metabolites in response to alcohol abstinence. Serum metabolic profiling was performed in 22 Cs, 147 HDs, and 33 patients with AC using ultraperformance liquid chromatography-tandem mass spectrometry.

Constitutive Androstane Receptor Differentially Regulates Bile Acid Homeostasis in Mouse Models of Intrahepatic Cholestasis.

Bile acid (BA) homeostasis is tightly regulated by multiple transcription factors, including farnesoid X receptor (FXR) and small heterodimer partner (SHP). We previously reported that loss of the FXR/SHP axis causes severe intrahepatic cholestasis, similar to human progressive familial intrahepatic cholestasis type 5 (PFIC5). In this study, we found that constitutive androstane receptor (CAR) is endogenously activated in double knockout (DKO) mice.