ABSTRACT
Background: Replacing SFAs with vegetable PUFAs has cardiometabolic
benefits, but the effects on liver fat are unknown. Increased
dietary n-6 PUFAs have, however, also been proposed to
promote inflammation—a yet unproven theory.
Objective: We investigated the effects of PUFAs on liver fat, systemic
inflammation, and metabolic disorders.
Design: We randomly assigned 67 abdominally obese subjects
(15% had type 2 diabetes) to a 10-wk isocaloric diet high in vegetable
n-6 PUFA (PUFA diet) or SFA mainly from butter (SFA diet),
without altering the macronutrient intake. Liver fat was assessed by
MRI and magnetic resonance proton (1H) spectroscopy (MRS).
Proprotein convertase subtilisin/kexin type-9 (PCSK9, a hepatic
LDL-receptor regulator), inflammation, and adipose tissue expression
of inflammatory and lipogenic genes were determined.
Results: A total of 61 subjects completed the study. Body weight
modestly increased but was not different between groups. Liver fat
was lower during the PUFA diet than during the SFA diet [betweengroup
difference in relative change from baseline; 16% (MRI; P ,
0.001), 34% (MRS; P = 0.02)]. PCSK9 (P = 0.001), TNF receptor-2
(P < 0.01), and IL-1 receptor antagonist (P = 0.02) concentrations were
lower during the PUFA diet, whereas insulin (P = 0.06) tended to be
higher during the SFA diet. In compliant subjects (defined as change in
serum linoleic acid), insulin, total/HDL-cholesterol ratio, LDL cholesterol,
and triglycerides were lower during the PUFA diet than during the
SFA diet (P < 0.05). Adipose tissue gene expression was unchanged.
Conclusions: Compared with SFA intake, n26 PUFAs reduce liver
fat and modestly improve metabolic status, without weight loss. A
high n-6 PUFA intake does not cause any signs of inflammation or
oxidative stress. Downregulation of PCSK9 could be a novel mechanism
behind the cholesterol-lowering effects of PUFAs. This trial was
registered at clinicaltrials.gov as NCT01038102. Am J Clin Nutr
2012;95:1003–12.
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