Preprint Article Version 1 NOT YET PEER-REVIEWED

Impaired Adipose Tissue Expansion Caused by LXR Activation is Associated with Insulin Resistance in HFD Mice

Version 1 : Received: 9 October 2016 / Approved: 10 October 2016 / Online: 10 October 2016 (07:56:30 CEST)

How to cite: Dong, Y.; Xu, Z.; Zhang, Z.; Yin, X.; Lin, X.; Pan, Q.; Li, H.; Zheng, F. Impaired Adipose Tissue Expansion Caused by LXR Activation is Associated with Insulin Resistance in HFD Mice. Preprints 2016, 2016100027 (doi: 10.20944/preprints201610.0027.v1). Dong, Y.; Xu, Z.; Zhang, Z.; Yin, X.; Lin, X.; Pan, Q.; Li, H.; Zheng, F. Impaired Adipose Tissue Expansion Caused by LXR Activation is Associated with Insulin Resistance in HFD Mice. Preprints 2016, 2016100027 (doi: 10.20944/preprints201610.0027.v1).

Abstract

Liver X receptors (LXR) are deemed as potential drug targets for atherosclerosis, whereas a role in adipose tissue expansion and its relation to insulin sensitivity remains unclear. To assess the metabolic effects of LXR activation, C57BL/6 mice on a high-fat diet (HFD) were treated with the dual LXRα/β agonist T0901317 (30 mg/kg per day) for 3 weeks. Differentiated 3T3-L1 was used for analysing the effect of T0901317 on glucose uptake.T0901317 reduced fat mass, accompanied by a massive fatty liver and lower adipokine levels in circulation of HFD mice. Increased adipocyte apoptosis and macrophage infiltration were found in epididymal fat of T0901317-treated HFD mice. In addition, T0901317 treatment promoted basal lipolysis, but blunted the anti-lipolytic action of insulin. Furthermore, LXR activation antagonized PPARγ target genes in epididymal fat and PPARγ-PPRE binding activity in 3T3-L1 adipocytes. Although the glucose tolerance was comparable to that in vehicle-treated HFD mice, the insulin tolerance was significantly decreased in T0901317-treated HFD mice, indicating decreased insulin sensitivity by T0901317 administration, and which was further supported by impaired insulin signalling found in epididymal fat and decreased insulin-induced glucose uptake in 3T3-L1 by T0901317administration. These findings reveal that LXR activation impairs adipose expansion which contributes to decreased insulin sensitivity.

Subject Areas

Liver X receptor (LXR); Peroxisome proliferator-activated receptor (PPARγ); Adipose expansion; Insulin resistance

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