Hypoxia factors and cytokines mRNA expression in visceral and subcutaneous adipose tissues (VAT and SCAT) in obese insulin resistant dogs. Effects of weight loss and fenofibrate treatment.

Abstract

Expansion of VAT and SCAT has been described to be associated with adipocyte hypoxia. That could lead to inflammation and insulin resistance (IR), but the link with obesity remains unclear. Our aim was to assess the expression of hypoxia and inflammation markers in VAT and SCAT, in obese IR dogs, and the effect of BW loss or fenofibrate treatment, which both improve insulin sensitivity.VAT and SCAT biopsies were taken from dogs in 3 different times: (a) when dogs were obese (group 1), (b) after they had been given fenofibrate (10 mg/kg BW) for 15 d (group 2) and (c) after they had been given a hypoenergetic diet and had recovered their ideal BW (group 3). mRNA expression of HIF‐variants 1, 4, 7, 8, HIF‐1A, IL‐1B, TNF‐A, IL‐1A, ubiquitine ligase and very long chain fatty acid (VLCFA) ligase‐5 was quantified using real time RT‐PCR.Fenofibrate did not affect BW (‐3%). Hypoenergetic diet resulted in a 25% BW lost. In VAT, mRNA expression was lower in groups 2 and 3, except IL‐1A and VLCFA‐ligase‐5. In SCAT, mRNA expression of only HIF‐1variant1 and VLCFA‐ligase‐5 was lower in the group 3 compared to group 1.These results confirm different metabolic responses in SCAT and VAT. They show a dramatic decrease in hypoxia factors expression in VAT in dogs after weight loss as well as at the end of the 15‐d fenofibrate treatment. This was concomitant to a decrease in cytokine expression, that could explain the improvement in insulin sensitivity.