Lipidomic Analysis of Liver and Adipose Tissue in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice Model Reveals Alterations in Lipid Metabolism by Weight Loss and Aerobic Exercise

Thomai Mouskeftara; Olga Deda; Grigorios Papadopoulos; Antonios Chatzigeorgiou; Helen Gika

doi:10.3390/molecules29071494

Lipidomic Analysis of Liver and Adipose Tissue in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice Model Reveals Alterations in Lipid Metabolism by Weight Loss and Aerobic Exercise

Molecules. 2024 Mar 27;29(7):1494. doi: 10.3390/molecules29071494.

Authors

Thomai Mouskeftara^{1

2}, Olga Deda^{1

2}, Grigorios Papadopoulos³, Antonios Chatzigeorgiou³, Helen Gika^{1

2}

Affiliations

¹ Laboratory of Forensic Medicine & Toxicology, Department of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
² Biomic AUTh, Center for Interdisciplinary Research and Innovation (CIRI-AUTH), Balkan Center B1.4, 10th km Thessaloniki-Thermi Rd, P.O. Box 8318, 57001 Thessaloniki, Greece.
³ Department of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Str., 11527 Athens, Greece.

Abstract

Detailed investigation of the lipidome remodeling upon normal weight conditions, obesity, or weight loss, as well as the influence of physical activity, can help to understand the mechanisms underlying dyslipidemia in metabolic conditions correlated to the emergence and progression of non-alcoholic fatty liver disease (NAFLD). C57BL/6 male mice were fed a normal diet (ND) or a high-fat diet (HFD) for 20 weeks. Subgroups within the high-fat diet (HFD) group underwent different interventions: some engaged in exercise (HFDex), others were subjected to weight loss (WL) by changing from the HFD to ND, and some underwent a combination of weight loss and exercise (WLex) during the final 8 weeks of the 20-week feeding period. To support our understanding, not only tissue-specific lipid remodeling mechanisms but also the cross-talk between different tissues and their impact on the systemic regulation of lipid metabolism are essential. Exercise and weight loss-induced specific adaptations in the liver and visceral adipose tissue lipidomes of mice were explored by the UPLC-TOF-MS/MS untargeted lipidomics methodology. Lipidomic signatures of ND and HFD-fed mice undergoing weight loss were compared with animals with and without physical exercise. Several lipid classes were identified as contributing factors in the discrimination of the groups by multivariate analysis models, such as glycerolipids, glycerophospholipids, sphingolipids, and fatty acids, with respect to liver samples, whereas triglycerides were the only lipid class identified in visceral adipose tissue. Lipids found to be dysregulated in HFD animals are related to well-established pathways involved in the biosynthesis of PC, PE, and TG metabolism. These show a reversing trend back to basic levels of ND when animals change to a normal diet after 12 weeks, whereas the impact of exercise, though in some cases it slightly enhances the reversing trend, is not clear.

Keywords: adipose tissue; de novo lipogenesis; exercise; lipidomics; liver; non-alcoholic fatty liver disease.

MeSH terms

Adipose Tissue
Animals
Diet, High-Fat / adverse effects
Fatty Acids
Lipid Metabolism
Lipidomics
Male
Mice
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease* / etiology
Tandem Mass Spectrometry
Weight Loss

Substances

Fatty Acids

Grants and funding

This research received no external funding.