Increased PUFA Content and 5-Lipoxygenase Pathway Expression Are Associated with Subcutaneous Adipose Tissue Inflammation in Obese Women with Type 2 Diabetes

Mattijs Heemskerk,Martin Giera,Ko Van Dijk,Hanno Pijl,Vanessa Van Harmelen,Mirjam Lips,Fatiha Bouazzaoui

doi:10.3390/nu7095362

Mattijs Heemskerk, Martin Giera + Show 5 more

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https://doi.org/10.3390/nu7095362

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Abstract

Obese women with type 2 diabetes mellitus (T2DM) have more inflammation in their subcutaneous white adipose tissue (sWAT) than age-and-BMI similar obese women with normal glucose tolerance (NGT). We aimed to investigate whether WAT fatty acids and/or oxylipins are associated with the enhanced inflammatory state in WAT of the T2DM women. Fatty acid profiles were measured in both subcutaneous and visceral adipose tissue (vWAT) of 19 obese women with NGT and 16 age-and-BMI similar women with T2DM. Oxylipin levels were measured in sWAT of all women. Arachidonic acid (AA) and docosahexaenoic acid (DHA) percentages were higher in sWAT, but not vWAT of the T2DM women, and AA correlated positively to the gene expression of macrophage marker CD68. We found tendencies for higher oxylipin concentrations of the 5-LOX leukotrienes in sWAT of T2DM women. Gene expression of the 5-LOX leukotriene biosynthesis pathway was significantly higher in sWAT of T2DM women. In conclusion, AA and DHA content were higher in sWAT of T2DM women and AA correlated to the increased inflammatory state in sWAT. Increased AA content was accompanied by an upregulation of the 5-LOX pathway and seems to have led to an increase in the conversion of AA into proinflammatory leukotrienes in sWAT.

Highlights

Obesity is closely associated with insulin resistance, type-2 diabetes mellitus (T2DM), dyslipidemia, hypertension, and cardiovascular disease
The gene expression of CD68 and the number of crown-like structures (CLS) per area adipose tissue on immunohistochemistry slides was used as an index for the extent of adipose tissue inflammation
Adipocyte sizes did not differ between normal glucose tolerance (NGT) and type 2 diabetes mellitus (T2DM) women both for subcutaneous white adipose tissue (sWAT) and vWAT

Summary

Introduction

Obesity is closely associated with insulin resistance, type-2 diabetes mellitus (T2DM), dyslipidemia, hypertension, and cardiovascular disease. The majority of obese individuals (~80%) will eventually develop metabolic disorders associated with a reduced life expectancy, there seems to be a subset of obese individuals that remains relatively insulin sensitive and metabolically healthy throughout life [2,3]. The reason why these individuals are unaffected is still not completely understood. From obese women with T2DM contained a larger number of crown-like structures (CLS) than sWAT of obese women with normal glucose tolerance (NGT) [4]. Metabolic health comprises more components than normal glucose tolerance, our data indicate that metabolically healthy and unhealthy obese women can be differentiated by the inflammatory status of their adipose tissue

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