Luukkonen · Diabetes care 2018 · Controlled overfeeding trial · n=38

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

Cited 436 times in the scientific literature.

Level 2 - randomized trial

Controlled feeding clinical trial comparing three overfeeding diets

PubMed 29844096 · doi:10.2337/dc18-0071 · record verified 2026-08-29

What was done

Thirty-eight overweight subjects (mean age 48 ± 2 years, BMI 31 ± 1 kg/m², baseline liver fat 4.7 ± 0.9%) were fed 1,000 extra kcal/day of saturated fat (SAT), unsaturated fat (UNSAT), or simple sugars (CARB) for 3 weeks. Investigators measured intrahepatic triglyceride content (IHTG via 1H-MRS), lipolysis ([2H5]glycerol) and hepatic de novo lipogenesis (DNL via 2H2O) at baseline and during euglycemic hyperinsulinemia, insulin resistance, endotoxemia, plasma ceramides, and adipose tissue gene expression before and after the 3-week intervention.

What was found

SAT overfeeding increased IHTG by +55%, which was significantly greater than UNSAT (+15%, P < 0.05). CARB overfeeding increased IHTG by +33% alongside a +98% increase in DNL. SAT significantly increased lipolysis, whereas UNSAT decreased it. SAT also induced insulin resistance and endotoxemia, and significantly increased multiple plasma ceramides. Each diet produced distinct alterations in adipose tissue gene expression.

Why it matters

This study indicates that the macronutrient source of excess caloric intake differentially drives hepatic steatosis pathways. Saturated fat causes substantially more liver fat accumulation, ceramide accumulation, and insulin resistance than equal caloric excesses of unsaturated fat or simple sugars.

Limits

The sample size was small (38 participants divided across three intervention arms), and the intervention period was brief (3 weeks). The study examined only overweight middle-aged adults, and the abstract does not state whether subjects were randomized or report long-term metabolic outcomes.

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