1 Department of Pathobiology, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA.
2 School of Kinesiology, University of Michigan, 1402 Washington Heights, Ann Arbor, MI 48109, USA.
3 Department of Kinesiology, University of Virginia, 405 Emmet St, Charlottesville, VA 22903, USA.
4 Radiology and Biomedical Engineering, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
5 Gastroenterology/Hepatology, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA.
6 Department of Pathobiology, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA; Gastroenterology/Hepatology, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA. Electronic address: John.Kirwan@pbrc.edu.
BACKGROUND AND AIMS:
Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive hepatic fat accumulation. Increased hepatic saturated fats and decreased hepatic polyunsaturated fats may be particularly lipotoxic, contributing to metabolic dysfunction. We compared hepatic lipid subspecies in adults with and without NAFLD, and examined links with hallmark metabolic and clinical characteristics of NAFLD.
METHODS AND RESULTS:
Nineteen adults with NAFLD (total hepatic fat:18.8 ± 0.1%) were compared to sixteen adults without NAFLD (total hepatic fat: 2.1 ± 0.01%). 1H-MRS was used to assess hepatic lipid subspecies. Methyl, allylic, methylene, and diallylic proton peaks were measured. Saturation, unsaturation, and polyunsaturation indices were calculated. Whole-body phenotyping in a subset of participants included insulin sensitivity (40 mU/m2 hyperinsulinemic-euglycemic clamps), CT-measured abdominal adipose tissue depots, exercise capacity, and serum lipid profiles. Participants with NAFLD exhibited more saturated and less unsaturated hepatic fat, accompanied by increased insulin resistance, total and visceral adiposity, triglycerides, and reduced exercise capacity compared to controls (all P < 0.05). All proton lipid peaks were related to insulin resistance and hypertriglyceridemia (P < 0.05).
Participants with NAFLD preferentially stored excess hepatic lipids as saturated fat, at the expense of unsaturated fat, compared to controls. This hepatic lipid profile was accompanied by an unhealthy metabolic phenotype.