Rosiglitazone Improves Insulin Resistance Mediated by 10,12 Conjugated Linoleic Acid in a Male Mouse Model of Metabolic Syndrome.

Abstract:

:Trans-10, cis-12 conjugated linoleic acid (10,12 CLA) is a dietary fatty acid that promotes weight loss and disproportionate fat loss. Obese mice fed a high-fat, high-sucrose (HFHS) diet containing 10,12 CLA are resistant to weight gain and contain markedly reduced subcutaneous fat and adiponectin, with a concurrent lack of improvement in insulin sensitivity despite significant weight loss. Taken together, 10,12 CLA promotes a phenotype resembling peroxisome proliferator-activated receptor (PPAR)γ antagonism. Because thiazolidinediones such as rosiglitazone (Rosi) are used clinically to improve insulin sensitivity by activating PPARγ, with particular efficacy in subcutaneous white adipose tissue, we hypothesized that Rosi would improve glucose metabolism in mice losing weight with 10,12 CLA. Obese low-density lipoprotein receptor-deficient mice were fed a HFHS control diet, or supplemented with 1% 10,12 CLA with or without Rosi (10 mg/kg) for 8 weeks. Body composition, glucose and insulin tolerance tests, tissue gene expression, and plasma lipid analyses were performed. Mice consuming 10,12 CLA with Rosi lost weight and body fat compared with control groups, but with a healthier redistribution of body fat toward more subcutaneous adipose tissue than with 10,12 CLA alone. Further, Rosi improved 10,12 CLA-mediated insulin resistance parameters and increased plasma and subcutaneous adipose tissue adiponectin levels without adverse effects on plasma or hepatic lipids. We conclude that cotreatment of mice with 10,12 CLA and Rosi promotes fat loss with a healthier fat distribution that leads to improved insulin sensitivity, suggesting that the combination treatment strategy of 10,12 CLA with Rosi could have therapeutic potential for obesity treatment.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Wang S,Goodspeed L,Turk KE,Houston B,den Hartigh LJ

doi

10.1210/en.2017-00213

subject

Has Abstract

pub_date

2017-09-01 00:00:00

pages

2848-2859

issue

9

eissn

0013-7227

issn

1945-7170

pii

3885817

journal_volume

158

pub_type

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