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Role of Dietary Fats in Modulating Cardiometabolic Risk During Moderate Weight Gain: A Randomized Double-Blind Overfeeding Trial (LIPOGAIN Study)
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, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
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2014 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 3, no 5, e001095Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Whether the type of dietary fat could alter cardiometabolic responses to a hypercaloric diet is unknown. In addition, subclinical cardiometabolic consequences of moderate weight gain require further study.

METHODS AND RESULTS: In a 7-week, double-blind, parallel-group, randomized controlled trial, 39 healthy, lean individuals (mean age of 27±4) consumed muffins (51% of energy [%E] from fat and 44%E refined carbohydrates) providing 750 kcal/day added to their habitual diets. All muffins had identical contents, except for type of fat; sunflower oil rich in polyunsaturated fatty acids (PUFA diet) or palm oil rich in saturated fatty acids (SFA diet). Despite comparable weight gain in the 2 groups, total: high-density lipoprotein (HDL) cholesterol, low-density lipoprotein:HDL cholesterol, and apolipoprotein B:AI ratios decreased during the PUFA versus the SFA diet (-0.37±0.59 versus +0.07±0.29, -0.31±0.49 versus +0.05±0.28, and -0.07±0.11 versus +0.01±0.07, P=0.003, P=0.007, and P=0.01 for between-group differences), whereas no significant differences were observed for other cardiometabolic risk markers. In the whole group (ie, independently of fat type), body weight increased (+2.2%, P<0.001) together with increased plasma proinsulin (+21%, P=0.007), insulin (+17%, P=0.003), proprotein convertase subtilisin/kexin type 9, (+9%, P=0.008) fibroblast growth factor-21 (+31%, P=0.04), endothelial markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin (+9, +5, and +10%, respectively, P<0.01 for all), whereas nonesterified fatty acids decreased (-28%, P=0.001).

CONCLUSIONS: Excess energy from PUFA versus SFA reduces atherogenic lipoproteins. Modest weight gain in young individuals induces hyperproinsulinemia and increases biomarkers of endothelial dysfunction, effects that may be partly outweighed by the lipid-lowering effects of PUFA.

CLINICAL TRIAL REGISTRATION URL: http://ClinicalTrials.gov. Unique identifier: NCT01427140.

Place, publisher, year, edition, pages
2014. Vol. 3, no 5, e001095
National Category
Nutrition and Dietetics
Identifiers
URN: urn:nbn:se:uu:diva-234939DOI: 10.1161/JAHA.114.001095ISI: 000357396800016PubMedID: 25319187OAI: oai:DiVA.org:uu-234939DiVA: diva2:758434
Funder
Swedish Research Council, K2012-55X-22081-01-3, K2013-55X-15075-10-3Swedish Heart Lung FoundationSwedish Diabetes Association
Available from: 2014-10-27 Created: 2014-10-27 Last updated: 2017-12-05Bibliographically 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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Iggman, DavidRosqvist, FredrikLarsson, AndersÄrnlöv, JohanRisérus, Ulf

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