Modification of subcutaneous white adipose tissue inflammation by omega-3 fatty acids is limited in human obesity-a double blind, randomised clinical trial
Helena L Fisk,
Caroline E Childs,
Elizabeth A Miles,
Robert Ayres,
Paul S Noakes,
Carolina Paras-Chavez,
Ondrej Kuda,
Jan Kopecký,
Elie Antoun,
Karen A Lillycrop,
Philip C Calder
Affiliations
Helena L Fisk
School of Human Development and Health, Faculty of Medicine, Southampton General Hospital, University of Southampton, IDS Building, MP887, Tremona Road, Southampton SO16 6YD, United Kingdom; Corresponding author.
Caroline E Childs
School of Human Development and Health, Faculty of Medicine, Southampton General Hospital, University of Southampton, IDS Building, MP887, Tremona Road, Southampton SO16 6YD, United Kingdom
Elizabeth A Miles
School of Human Development and Health, Faculty of Medicine, Southampton General Hospital, University of Southampton, IDS Building, MP887, Tremona Road, Southampton SO16 6YD, United Kingdom
Robert Ayres
School of Human Development and Health, Faculty of Medicine, Southampton General Hospital, University of Southampton, IDS Building, MP887, Tremona Road, Southampton SO16 6YD, United Kingdom
Paul S Noakes
School of Human Development and Health, Faculty of Medicine, Southampton General Hospital, University of Southampton, IDS Building, MP887, Tremona Road, Southampton SO16 6YD, United Kingdom; Medical School, University of Notre Dame Australia, Fremantle, Australia
Carolina Paras-Chavez
School of Human Development and Health, Faculty of Medicine, Southampton General Hospital, University of Southampton, IDS Building, MP887, Tremona Road, Southampton SO16 6YD, United Kingdom
Ondrej Kuda
Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
Jan Kopecký
Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
Elie Antoun
School of Human Development and Health, Faculty of Medicine, Southampton General Hospital, University of Southampton, IDS Building, MP887, Tremona Road, Southampton SO16 6YD, United Kingdom
Karen A Lillycrop
School of Human Development and Health, Faculty of Medicine, Southampton General Hospital, University of Southampton, IDS Building, MP887, Tremona Road, Southampton SO16 6YD, United Kingdom; School of Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, United Kingdom
Philip C Calder
School of Human Development and Health, Faculty of Medicine, Southampton General Hospital, University of Southampton, IDS Building, MP887, Tremona Road, Southampton SO16 6YD, United Kingdom; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, United Kingdom
Summary: Background: Obesity is associated with enhanced inflammation. However, investigation in human subcutaneous white adipose tissue (scWAT) is limited and the mechanisms by which inflammation occurs have not been well elucidated. Marine long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have anti-inflammatory actions and may reduce scWAT inflammation. Methods: Subcutaneous white adipose tissue (scWAT) biopsies were collected from individuals living with obesity (n=45) and normal weight individuals (n=39) prior to and following a 12-week intervention with either 3 g/day of a fish oil concentrate (providing 1.1 g eicosapentaenoic acid (EPA) + 0.8 g docosahexaenoic acid (DHA)) or 3 g/day of corn oil. ScWAT fatty acid, oxylipin, and transcriptome profiles were assessed by gas chromatography, ultra-pure liquid chromatography tandem mass spectrometry, RNA sequencing and qRT-PCR, respectively. Findings: Obesity was associated with greater scWAT inflammation demonstrated by lower concentrations of specialised pro-resolving mediators (SPMs) and hydroxy-DHA metabolites and an altered transcriptome with differential expression of genes involved in LC n-3 PUFA activation, oxylipin synthesis, inflammation, and immune response. Intervention with LC n-3 PUFAs increased their respective metabolites including the SPM precursor 14-hydroxy-DHA in normal weight individuals and decreased arachidonic acid derived metabolites and expression of genes involved in immune and inflammatory response with a greater effect in normal weight individuals. Interpretation: Downregulated expression of genes responsible for fatty acid activation and metabolism may contribute to an inflammatory oxylipin profile and limit the effects of LC n-3 PUFAs in obesity. There may be a need for personalised LC n-3 PUFA supplementation based on obesity status. Funding: European Commission Seventh Framework Programme (Grant Number 244995) and Czech Academy of Sciences (Lumina quaeruntur LQ200111901).
