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Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Center for Clinical Research Dalarna.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
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2012 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 95, no 5, 1003-1012 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2012. Vol. 95, no 5, 1003-1012 p.
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-172856DOI: 10.3945/ajcn.111.030114ISI: 000303140700004PubMedID: 22492369OAI: oai:DiVA.org:uu-172856DiVA: diva2:515839
Available from: 2012-04-16 Created: 2012-04-16 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Dietary Fatty Acids and Cardiometabolic Risk: Influence on Lipoproteins, Insulin Resistance and Liver Fat
Open this publication in new window or tab >>Dietary Fatty Acids and Cardiometabolic Risk: Influence on Lipoproteins, Insulin Resistance and Liver Fat
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis was to investigate how dietary fatty acids affect the risk for cardiometabolic disease, i.e. cardiovascular disease (CVD), type 2 diabetes and obesity. The overall hypothesis was that unsaturated fatty acids and especially the predominant polyunsaturated fatty acid (PUFA) linoleic acid (LA), 18:2n-6, would decrease cardiometabolic risk compared with saturated fatty acids (SFAs), in line with current recommendations to partly replace dietary SFA with PUFA.

Papers I and V were observational studies based on the community-based cohort Uppsala Longitudinal Study of Adult Men (ULSAM). Adipose tissue fatty acid composition was determined as biomarker for dietary fat intake. Studies II, III and IV were randomised short-term interventions on human volunteers, in which different dietary fats were provided to the participants.

In 71-year-old men, adipose tissue LA and α-linolenic acid (18:3n-3) were associated with insulin sensitivity (euglycaemic clamp), although this association was diminished for LA after adjusting for lifestyle variables. Different SFA displayed divergent associations; only palmitic acid (16:0) was inversely associated with insulin sensitivity (Paper I). In Cox regression analyses, LA was modestly associated with decreased all-cause mortality, but not CVD mortality during 15 years follow-up (Paper V).

In a 3+3-week cross-over study on 20 weight-stable volunteers with dyslipidaemia, all foods were provided. A rapeseed oil-based diet distinctly lowered low-density lipoprotein cholesterol and triglycerides compared with a dairy-fat based diet (butter, cream and fatty cheese). Insulin sensitivity or coagulation factors were not affected (Paper II).

In a 10-week randomised trial on 67 abdominally obese participants, PUFA (mostly sunflower oil) decreased liver fat compared with SFA (mostly butter) under isocaloric conditions. In individuals considered highly compliant to study diets, lipoproteins were also decreased during the PUFA diet (Paper III).

In a 7-week double-blind randomised trial on 41 healthy volunteers, PUFA (sunflower oil) decreased the total:HDL cholesterol ratio compared with SFA (palm oil) during moderate weight gain (1.5 kg) (Paper IV).

In conclusion, LA (PUFA) intake is associated with decreased cardiometabolic risk compared with higher SFA intake, overall supporting a beneficial role of non-tropical vegetable oils in place of solid fats in preventing fatty liver and cardiometabolic disorders.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 74 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1111
Keyword
Linoleic acid, Palmitic acid, PUFA, SFA, n-6 fatty acids
National Category
Medical and Health Sciences
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-252066 (URN)978-91-554-9264-9 (ISBN)
Public defence
2015-08-21, Auditorium Minus, Museum Gustavianum, Akademigatan 3, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2015-05-29 Created: 2015-04-28 Last updated: 2015-07-07Bibliographically approved

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Bjermo, HelenaIggman, DavidKullberg, JoelJohansson, LarsBerglund, JohanBasu, SamarCederholm, TommyAhlström, HåkanRisérus, Ulf

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