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Adipose tissue fatty acid chain length and mono-unsaturation increases with obesity and insulin resistance.


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Authors

Yew Tan, Chong 
Virtue, Samuel 
Murfitt, Steven 
Roberts, Lee D 
Phua, Yi Hui 

Abstract

The non-essential fatty acids, C18:1n9, C16:0, C16:1n7, C18:0 and C18:1n7 account for over 75% of fatty acids in white adipose (WAT) triacylglycerol (TAG). The relative composition of these fatty acids (FA) is influenced by the desaturases, SCD1-4 and the elongase, ELOVL6. In knock-out models, loss of SCD1 or ELOVL6 results in reduced Δ9 desaturated and reduced 18-carbon non-essential FA respectively. Both Elovl6 KO and SCD1 KO mice exhibit improved insulin sensitivity. Here we describe the relationship between WAT TAG composition in obese mouse models and obese humans stratified for insulin resistance. In mouse models with increasing obesity and insulin resistance, there was an increase in scWAT Δ9 desaturated FAs (SCD ratio) and FAs with 18-carbons (Elovl6 ratio) in mice. Data from mouse models discordant for obesity and insulin resistance (AKT2 KO, Adiponectin aP2-transgenic), suggested that scWAT TAG Elovl6 ratio was associated with insulin sensitivity, whereas SCD1 ratio was associated with fat mass. In humans, a greater SCD1 and Elovl6 ratio was found in metabolically more harmful visceral adipose tissue when compared to subcutaneous adipose tissue.

Description

Keywords

Acetyltransferases, Adenosine Deaminase, Adipose Tissue, White, Animals, Fatty Acid Elongases, Fatty Acids, Female, Insulin Resistance, Male, Mice, Mice, Knockout, Mice, Obese, Obesity, Severity of Illness Index, Triglycerides

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

5

Publisher

Springer Science and Business Media LLC
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/H013539/2)
Biotechnology and Biological Sciences Research Council (BB/H013539/1)
British Heart Foundation (None)
Biotechnology and Biological Sciences Research Council (BB/H002731/1)
Medical Research Council (MC_G0802535)
Medical Research Council (MC_UU_12012/2)
Biotechnology and Biological Sciences Research Council (BB/J009865/1)
Medical Research Council (G0400192)
Medical Research Council (G0600717)
Medical Research Council (G0802051)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (MC_UU_12012/5/B)
Medical Research Council (MC_PC_13030)
Medical Research Council (MC_PC_12012)
Medical Research Council (G0600717/1)
We thank the BBSRC, MRC and Wellcome trust for funding this work. The research leading to these results has also received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. We thank the MRC-MDU DMC for supporting all animal experiments in this publication. The authors state they have no conflict of interest, either financial or scientific.