Preprint Article Version 1 NOT YET PEER-REVIEWED

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

  1. Department of Endocrinology, Sir Run Run Shaw Hospital Affiliated with School of Zhejiang University, 3 East Qingchun Road, Hangzhou 310016, China
  2. Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Sir Run Run Shaw Hospital Affiliated with School of Zhejiang University, 3 East Qingchun Road, Hangzhou 310016, China
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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