Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis

Abstract

To elucidate the contributions of specific lipid species to metabolic traits, we integrated global hepatic lipid data with other omics measures and genetic data from a cohort of about 100 diverse inbred strains of mice fed a high-fat/high-sucrose diet for 8 weeks. Association mapping, correlation, structure analyses, and network modeling revealed pathways and genes underlying these interactions. In particular, our studies lead to the identification of Ifi203 and Map2k6 as regulators of hepatic phosphatidylcholine homeostasis and triacylglycerol accumulation, respectively. Our analyses highlight mechanisms for how genetic variation in hepatic lipidome can be linked to physiological and molecular phenotypes, such as microbiota composition.

Accumulation of cholesterol, triglycerides and ceramides in hepatocellular carcinomas of diethylnitrosamine injected mice

“…This recent study used C57BL/6 mice [ 61 ] whereas C3H/HeNRj mice were analyzed in the current investigation. Different mouse strains exhibit variations in their liver lipidome and in their response to diets [ 77 ]. In addition, the lipidome can be affected by age, gender, and circadian rhythm [ 78 ].…”

PharmOmics: A species- and tissue-specific drug signature database and gene-network-based drug repositioning tool

“…Fluvastatin and aspirin were tested using a mouse steatosis model induced by a high-fat high-sucrose (HFHS) Western diet, which has been previously used to study NAFLD ( Hui et al., 2015 ; Chella Krishnan et al., 2018 , 2021 ; Norheim et al., 2021 ). Key genes identified in this diet-induced NAFLD model ( Chella Krishnan et al., 2018 ) were known NAFLD-associated genes ( Chakravarthy et al., 2009 ; Wu et al., 2013 ) and reproducible in independent human studies ( Lee et al., 2017 ), supporting its utility as a model for this disease.…”

“…Since drug repositioning was done using steatosis gene signatures, we validated the predicted drugs using a diet-induced steatosis mouse model which has been previously ( Hui et al., 2015 ; Chella Krishnan et al., 2018 , 2021 ; Norheim et al., 2021 ) used to study NAFLD. Briefly, seven-week old C57BL/6J male mice were purchased from the Jackson Laboratory (Bar Harbor, ME).…”

Characterization of Lipids in Saliva, Tears and Minor Salivary Glands of Sjögren’s Syndrome Patients Using an HPLC/MS-Based Approach

“…Untargeted comprehensive lipidomic analysis was performed on saliva, minor salivary glands and tear fluid isolated from Schirmer paper using HPLC coupled to time-of-flight mass spectrometry (TOF-MS). The platform allows determination of glycerolipids, glycerophospholipids, cardiolipins, sphingolipids, free fatty acids, free cholesterol, cholesterol esters, wax esters, diesters and OAHFA, as described in previously published work [47,48]. In total, 86, 146 and 132 specific lipids within these classes were identified in, saliva, minor salivary glands and tears, respectively.…”

“…In total, 86, 146 and 132 specific lipids within these classes were identified in, saliva, minor salivary glands and tears, respectively. A 1260 Agilent chromatographic system comprising an autosampler, a binary pump and a TCC column heater unit coupled to a TOF-MS with Agilent JetStream ionization module for enhanced sensitivity was used and operated in both positive and negative ionization mode, as previously described [47,48]. To obtain highresolution chromatographic separation of the lipids, a C18-EVO Kinetex analytical column (column dimensions 2.1 × 150 mm, 2.6 µm) was used with a flow rate of 0.7 mL/min.…”