Hepatic Lipid Profiling in Fatty Liver Disease—Degree of Saturation Matters

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Introduction: Hepatic lipids can take on several storage forms, which vary by degree of saturation. The health consequences of hepatic lipids may vary by storage type, in that polyunsaturated lipids may be favorable, while saturated lipids may be detrimental. The purpose of this study was to determine if the degree of hepatic lipid saturation is related to hallmark characteristics of obesity-related nonalcoholic fatty liver disease, including low exercise capacity and insulin resistance. Methods: Hepatic lipid profiles were measured using 1H-MRS in 30 adults (55 ± 13.4 years, 31 ± 5.5 kg/m2). Methyl, allylic, methylene, and diallylic peaks were quantified. Hepatic lipids were categorized by storage form, including polyunsaturation, unsaturation, and saturation indices. Explored health correlates include exercise capacity, 40 mU/m2 euglycemic-hyperinsulinemic clamps, and abdominal CT scans. Results: 20 participants met the diagnostic criteria for nonalcoholic fatty liver disease (total hepatic fat > 5%). Hepatic polyunsaturation index was positively related to absolute maximal oxygen uptake (r=0.41, P=0.04). In addition, hepatic saturation index was inversely related to clamp-derived skeletal muscle insulin sensitivity (r=-0.48, P=0.007). Discussion/Conclusion: We found that the hepatic polyunsaturation index was positivity related to exercise capacity, independent of body weight. Conversely, saturation index was inversely related to insulin sensitivity. These data show that the health consequences of hepatic fat vary by storage type. Insulin resistance is associated with a higher degree of saturation and a consequential lower degree of polyunsaturation. Thus, effective treatment strategies for nonalcoholic fatty liver disease should not only aim to reduce total hepatic lipid content, but also promote a shift in storage type, from saturation to polyunsaturation, in order to maximize metabolic benefit. Disclosure M.L. Erickson: None. J.M. Haus: None. C. Flask: None. J.P. Kirwan: None.