Saturated fat is more metabolically harmful for the human liver than unsaturated fat or simple sugars

• 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. © 2018 by the American Diabetes Association.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

ceramide derivative

saturated fatty acid

sugar

triacylglycerol

unsaturated fatty acid

edible oil

fatty acid

insulin

monosaccharide

adipose tissue

adult

body weight gain

carbohydrate metabolism

clinical article

Conference Paper

controlled study

dietary intake

endotoxemia

female

food composition

gene expression

high calorie diet

human

hyperinsulinemia

insulin resistance

lipid blood level

lipid metabolism

lipolysis

macronutrient

male

nonalcoholic fatty liver

obesity

proton nuclear magnetic resonance

blood

clinical trial

complication

feeding behavior

liver

metabolism

middle aged

physiology

Adipose Tissue

Adult

Carbohydrate Metabolism

Dietary Fats, Unsaturated

Fatty Acids

Feeding Behavior

Female

Humans

Insulin

Insulin Resistance

Lipid Metabolism

Liver

Male

Middle Aged

Monosaccharides

Non-alcoholic Fatty Liver Disease

Overweight

Triglycerides

Weight Gain

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