Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial1234

https://doi.org/10.3945/ajcn.111.030114Get rights and content
Under an Elsevier user license
open archive

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 [between-group 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, n-6 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.

Abbreviations:

ALT
alanine aminotransferase
CAD
coronary artery disease
Ct
comparative threshold cycle
IL-1RA
IL-1 receptor antagonist
MRS
magnetic resonance proton (1H) spectroscopy
NAFLD
nonalcoholic fatty liver disease
OGTT
oral-glucose-tolerance test
PCSK9
proprotein convertase subtilisin/kexin type-9
SCD-1
stearoyl-CoA desaturase 1
TNF-R2
TNF receptor-2

Cited by (0)

1

From the Departments of Public Health and Caring Sciences (HB, DI, SB, TC, and UR) and Radiology (JK, LJ, JB, and HA), Uppsala University, Uppsala, Sweden; the Center for Clinical Research Dalarna, Falun, Sweden (DI); the Department of Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden (ID and PA); AstraZeneca R&D, Mölndal, Sweden (LJ); the Department of Endocrinology, Metabolism & Diabetes and Center for Biosciences, Department of Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden (LP and MR); the Department of Clinical Chemistry, University of Eastern Finland and Eastern Finland Laboratory Centre, Kuopio, Finland (KP); the Laboratory of Biochemistry, Molecular Biology and Nutrition, Universite d’Auvergne, Clermont-Ferrand, France (SB); the Institute of Public Health and Clinical Nutrition, Clinical Nutrition, University of Eastern Finland, Kuopio, Finland (MU); and the Research Unit, Kuopio University Hospital, Kuopio, Finland (MU).

2

Presented orally and as a poster at the 29th International Symposium on Diabetes and Nutrition of the Nutrition Study Group, Rome, Italy, 1 July 2011.

3

Supported by a grant from the Swedish Council for Working Life and Social Research.

4

Address correspondence and reprint requests to U Risérus, Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala Science Park, 75185 Uppsala, Sweden. E-mail: [email protected].