Overeating Saturated Fat Promotes Fatty Liver and Ceramides Compared With Polyunsaturated Fat: A Randomized Trial

Fredrik Rosqvist, Joel Kullberg, Marcus Ståhlman, Jonathan Cedernaes, Kerstin Heurling, Hans-Erik Johansson, David Iggman, Helena Wilking, Anders Larsson, Olof Eriksson, Lars Johansson, Sara Straniero, Mats Rudling, Gunnar Antoni, Mark Lubberink, Marju Orho-Melander, Jan Borén, Håkan Ahlström, Ulf Risérus, Fredrik Rosqvist, Joel Kullberg, Marcus Ståhlman, Jonathan Cedernaes, Kerstin Heurling, Hans-Erik Johansson, David Iggman, Helena Wilking, Anders Larsson, Olof Eriksson, Lars Johansson, Sara Straniero, Mats Rudling, Gunnar Antoni, Mark Lubberink, Marju Orho-Melander, Jan Borén, Håkan Ahlström, Ulf Risérus

Abstract

Context: Saturated fatty acid (SFA) vs polyunsaturated fatty acid (PUFA) may promote nonalcoholic fatty liver disease by yet unclear mechanisms.

Objective: To investigate if overeating SFA- and PUFA-enriched diets lead to differential liver fat accumulation in overweight and obese humans.

Design: Double-blind randomized trial (LIPOGAIN-2). Overfeeding SFA vs PUFA for 8 weeks, followed by 4 weeks of caloric restriction.

Setting: General community.

Participants: Men and women who are overweight or have obesity (n = 61).

Intervention: Muffins, high in either palm (SFA) or sunflower oil (PUFA), were added to the habitual diet.

Main outcome measures: Lean tissue mass (not reported here). Secondary and exploratory outcomes included liver and ectopic fat depots.

Results: By design, body weight gain was similar in SFA (2.31 ± 1.38 kg) and PUFA (2.01 ± 1.90 kg) groups, P = 0.50. SFA markedly induced liver fat content (50% relative increase) along with liver enzymes and atherogenic serum lipids. In contrast, despite similar weight gain, PUFA did not increase liver fat or liver enzymes or cause any adverse effects on blood lipids. SFA had no differential effect on the accumulation of visceral fat, pancreas fat, or total body fat compared with PUFA. SFA consistently increased, whereas PUFA reduced circulating ceramides, changes that were moderately associated with liver fat changes and proposed markers of hepatic lipogenesis. The adverse metabolic effects of SFA were reversed by calorie restriction.

Conclusions: SFA markedly induces liver fat and serum ceramides, whereas dietary PUFA prevents liver fat accumulation and reduces ceramides and hyperlipidemia during excess energy intake and weight gain in overweight individuals.

Trial registration: ClinicalTrials.gov NCT02211612.

Copyright © 2019 Endocrine Society.

Figures

Figure 1.
Figure 1.
Difference in blood lipids between groups at end of intervention, adjusted for baseline values. Differences represent “SFA vs PUFA”; i.e., a positive change means the variable was higher on the SFA-rich diet. Bars are SE. Analyzed with ANCOVA. *P < 0.05.
Figure 2.
Figure 2.
Change in (A) liver fat (percentage points), (B) pancreas fat (percentage points), (C) visceral fat, and (D) total body fat in the SFA (n = 30) and PUFA (n = 30) groups. The boxes represent the IQR and the lines within the median. Analyzed with ANCOVA, adjusted for baseline value.
Figure 3.
Figure 3.
Relative change from baseline (%) in serum. (A) Total ceramide species, (B) C16-containing ceramide species, (C) C18-containing ceramide species, (D) C20-containing ceramide species, (E) C24-containing ceramide species, and (F) C24:1-containing ceramide species in SFA (n = 30) and PUFA (n = 30) groups. Analyzed with ANCOVA, adjusted for baseline value.
Figure 4.
Figure 4.
Spearman correlations between change in pancreatic palmitate uptake (SUV 60 min) and change in (A) total serum Cer, (B) total serum DiCer, (C) total serum GluCer, and (D) total serum LacCer in 10 men.

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