Dataset Information

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.

SUBMITTER: Norheim F

PROVIDER: S-EPMC7792507 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Norheim Frode F Chella Krishnan Karthickeyan K Bjellaas Thomas T Vergnes Laurent L Pan Calvin C Parks Brian W BW Meng Yonghong Y Lang Jennifer J Ward James A JA Reue Karen K Mehrabian Margarete M Gundersen Thomas E TE Péterfy Miklós M Dalen Knut T KT Drevon Christian A CA Hui Simon T ST Lusis Aldons J AJ Seldin Marcus M MM

Molecular systems biology 20210101 1

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 p ...[more]

PMID: 33417276

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Project description:BackgroundMenopause is associated with significant hormonal changes that result in increased total body fat and abdominal fat, amplifying the risk for metabolic syndrome and diseases such as diabetes, cardiovascular disease and cancer in postmenopausal women. Intermittent fasting regimens hold significant health benefit promise for obese humans, however, regimens that include extreme daytime calorie restriction or daytime fasting are generally associated with hunger and irritability, hampering long-term compliance and adoption in the clinical setting. Time-restricted feeding (TRF), a regimen allowing eating only during a specific period in the normal circadian feeding cycle, without calorie restriction, may increase compliance and provide a more clinically viable method for reducing the detrimental metabolic consequences associated with obesity.MethodsWe tested TRF as an intervention in a mouse model of postmenopausal obesity. Metabolic parameters were measured using Clinical Laboratory Animal Monitoring System (CLAMS) and we carried out glucose tolerance tests. We also stained liver sections with oil red O to examine steatosis and measured gene expression related to gluconeogenesis.ResultsPreexisting metabolic disease was significantly attenuated during 7 weeks of TRF. Despite having access to the same high fat diet (HFD) as ad libitum fed (ALF) mice, TRF mice experienced rapid weight loss followed by a delayed improvement in insulin resistance and a reduced severity of hepatic steatosis by having access to the HFD for only 8h during their normal nocturnal feeding period. The lower respiratory exchange ratio in the TRF group compared with the ALF group early in the dark phase suggested that fat was the predominant fuel source in the TRF group and correlated with gene expression analyses that suggested a switch from gluconeogenesis to ketogenesis. In addition, TRF mice were more physically active than ALF fed mice.ConclusionsOur data support further analysis of TRF as a clinically viable form of intermittent fasting to improve metabolic health due to obesity.

Dataset Information

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

Publications

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

Similar Datasets

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