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Diabetes Care. 2018 Aug;41(8):1732-1739. doi: 10.2337/dc18-0071. Epub 2018 May 29.

Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars.

Author information

1
Minerva Foundation Institute for Medical Research, Helsinki, Finland.
2
Department of Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
3
Systems Immunity University Research Institute and Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, U.K.
4
Sorbonne Universités, INSERM, UMRS 1166, Nutriomics Team, Institute of Cardiometabolism and Nutrition, Paris, France.
5
Steno Diabetes Center Copenhagen, Gentofte, Denmark.
6
Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche, Pisa, Italy.
7
Immunobiology Research Program, Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.
8
Helsinki Medical Imaging Centre, Radiology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
9
School of Medical Sciences, Örebro University, Örebro, Sweden.
10
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
11
Department of Chemistry, Örebro University, Örebro, Sweden.
12
Lund University, Malmö, Sweden.
13
Obesity Research Unit, Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland.
14
Nutrition Department, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
15
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K.
16
Minerva Foundation Institute for Medical Research, Helsinki, Finland hannele.yki-jarvinen@helsinki.fi.

Abstract

OBJECTIVE:

Nonalcoholic fatty liver disease (i.e., increased intrahepatic triglyceride [IHTG] content), predisposes to type 2 diabetes and cardiovascular disease. Adipose tissue lipolysis and hepatic de novo lipogenesis (DNL) are the main pathways contributing to IHTG. We hypothesized that dietary macronutrient composition influences the pathways, mediators, and magnitude of weight gain-induced changes in IHTG.

RESEARCH DESIGN AND METHODS:

We overfed 38 overweight subjects (age 48 ± 2 years, BMI 31 ± 1 kg/m2, liver fat 4.7 ± 0.9%) 1,000 extra kcal/day of saturated (SAT) or unsaturated (UNSAT) fat or simple sugars (CARB) for 3 weeks. We measured IHTG (1H-MRS), pathways contributing to IHTG (lipolysis ([2H5]glycerol) and DNL (2H2O) basally and during euglycemic hyperinsulinemia), insulin resistance, endotoxemia, plasma ceramides, and adipose tissue gene expression at 0 and 3 weeks.

RESULTS:

Overfeeding SAT increased IHTG more (+55%) than UNSAT (+15%, P < 0.05). CARB increased IHTG (+33%) by stimulating DNL (+98%). SAT significantly increased while UNSAT decreased lipolysis. SAT induced insulin resistance and endotoxemia and significantly increased multiple plasma ceramides. The diets had distinct effects on adipose tissue gene expression.

CONCLUSIONS:

Macronutrient composition of excess energy influences pathways of IHTG: CARB increases DNL, while SAT increases and UNSAT decreases lipolysis. SAT induced the greatest increase in IHTG, insulin resistance, and harmful ceramides. Decreased intakes of SAT could be beneficial in reducing IHTG and the associated risk of diabetes.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02133144.

PMID:
29844096
DOI:
10.2337/dc18-0071
[Indexed for MEDLINE]

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