Increased hepatic fatty acid polyunsaturation precedes ectopic lipid deposition in the liver in adaptation to high-fat diets in mice
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We monitored hepatic lipid content (HLC) and fatty acid (FA) composition in the context of enhanced lipid handling induced by a metabolic high-fat diet (HFD) challenge and fasting.
Materials and methods
Mice received a control diet (10% of kilocalories from fat, N = 14) or an HFD (45% or 60% of kilocalories from fat, N = 10 and N = 16, respectively) for 26 weeks. A subset of five mice receiving an HFD (60% of kilocalories from fat) were switched to the control diet for the final 7 weeks. At nine time points, magnetic resonance spectroscopy was performed in vivo at 14.1 T, interleaved with glucose tolerance tests.
Glucose intolerance promptly developed with the HFD, followed by a progressive increase of fasting insulin level, simultaneously with that of HLC. These metabolic defects were normalized by dietary reversal. HFD feeding immediately increased polyunsaturation of hepatic FA, before lipid accumulation. Fasting-induced changes in hepatic lipids (increased HLC and FA polyunsaturation, decreased FA monounsaturation) in control-diet-fed mice were not completely reproduced in HFD-fed mice, not even after dietary reversal.
A similar adaptation of hepatic lipids to both fasting and an HFD suggests common mechanisms of lipid trafficking from adipose tissue to the liver. Altered hepatic lipid handling with fasting indicates imperfect metabolic recovery from HFD exposure.
KeywordsInsulin resistance Liver Nuclear Magnetic Resonance Nutrition Obesity Polyunsaturated fat
This work received financial support from the Swiss National Science Foundation (grant 148250 to JMND), the Centre d’Imagerie BioMédicale of the University of Lausanne, the University of Geneva, the University Hospital of Geneva, the University Hospital of Lausanne, the École Polythenique Fédérale de Lausanne, the Leenaards Foundation, and the Louis-Jeantet Foundation. The authors are grateful to Blanca Lizarbe for her help with animal monitoring. The authors are also grateful to Anne-Catherine Clerc and Analina da Silva for technical support.
AFS designed the study, performed liver magnetic resonance spectroscopy experiments, collected, analyzed, and interpreted data, and drafted the manuscript. JMND designed the study, edited the manuscript, and contributed to the discussion. RG edited the manuscript and contributed to the discussion.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
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