Adipose tissue inflammation and altered lipid signaling in obesity, and the effects of long chain omega-3 polyunsaturated fatty acid supplementation.

Obesity is an excess of adipose tissue (AT) and is linked with increased inflammation that enhances risk of type-2 diabetes and cardiovascular disease. The BIOCLAIMS Study assessed AT inflammation in obesity, and responses to chronic omega-3 fatty acid (FA) supplementation. AT biopsies were collected pre- and post-12-week supplementation with 1.1g EPA + 0.8g DHA/day or corn oil. AT FA composition, AT lipid mediator profile, AT whole transcriptome expression, morphology, and immune cell infiltration were assessed by gas chromatography, coupled UPLC-mass spectrometry, RNA-Sequencing, and immuno-histochemical staining respectively.

Obesity was associated with dysregulated FA and lipid mediator profiles exhibiting higher concentrations of arachidonic acid (AA) and respective oxylipins, lower concentrations of DHA oxylipins, and alteration of the endocannabinoid system (ECS) (P < 0.05), as well as altered transcriptome expression suggestive of enhanced inflammation, immune response, tissue remodelling, and expansion. Dysregulated tissue expansion and inflammation was concordant with tissue morphology in which obesity was associated with adipocyte hypertrophy and immune cell infiltration (P < 0.05).
Chronic supplementation with EPA+DHA increased concentrations of AT omega-3 FAs (P < 0.01) and derived oxylipins, and decreased AA oxylipins, particularly modulating the ECS, predominantly in normal weight individuals (P < 0.05). EPA+DHA modulated AT transcriptome suggesting promotion of tissue remodelling and downregulation of cell differentiation and chronic inflammatory response (P < 0.05).

These data suggest altered lipid signalling, tissue remodelling and enhance inflammation are associated with obesity. EPA+DHA are able to modulate synthesis of EPA, DHA and AA derived oxylipins and transcriptome expression, but obesity may involve resistance to these effects. AT of metabolically healthy obese individuals is sensitive to dietary lipid manipulation but exhibits differences in the handling of these lipids which may link to altered transcriptome and. Restoring lipid metabolism and oxylipin + ECS signalling may be a route to resolving inflammation in obesity.