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J Biol Chem. 2015 May 1;290(18):11547-56. doi: 10.1074/jbc.M114.628487. Epub 2015 Mar 17.

Increasing adipocyte lipoprotein lipase improves glucose metabolism in high fat diet-induced obesity.

Author information

1
From the Department of Medicine, Division of Endocrinology, Barnstable Brown Diabetes and Obesity Center.
2
the Department of Molecular Biology and Genetics, Faculty of Life Sciences, Mugla Sitki Kocman University, 48000 Mugla, Turkey.
3
Division of Cardiovascular Medicine.
4
Department of Biostatistics, College of Public Health.
5
Department of Pharmacology and Nutritional Sciences, and.
6
Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky 40536 and.
7
From the Department of Medicine, Division of Endocrinology, Barnstable Brown Diabetes and Obesity Center, bfinlin@uky.edu.

Abstract

Lipid accumulation in liver and skeletal muscle contributes to co-morbidities associated with diabetes and obesity. We made a transgenic mouse in which the adiponectin (Adipoq) promoter drives expression of lipoprotein lipase (LPL) in adipocytes to potentially increase adipose tissue lipid storage. These mice (Adipoq-LPL) have improved glucose and insulin tolerance as well as increased energy expenditure when challenged with a high fat diet (HFD). To identify the mechanism(s) involved, we determined whether the Adipoq-LPL mice diverted dietary lipid to adipose tissue to reduce peripheral lipotoxicity, but we found no evidence for this. Instead, characterization of the adipose tissue of the male mice after HFD challenge revealed that the mRNA levels of peroxisome proliferator-activated receptor-γ (PPARγ) and a number of PPARγ-regulated genes were higher in the epididymal fat pads of Adipoq-LPL mice than control mice. This included adiponectin, whose mRNA levels were increased, leading to increased adiponectin serum levels in the Adipoq-LPL mice. In many respects, the adipose phenotype of these animals resembles thiazolidinedione treatment except for one important difference, the Adipoq-LPL mice did not gain more fat mass on HFD than control mice and did not have increased expression of genes in adipose such as glycerol kinase, which are induced by high affinity PPAR agonists. Rather, there was selective induction of PPARγ-regulated genes such as adiponectin in the adipose of the Adipoq-LPL mice, suggesting that increasing adipose tissue LPL improves glucose metabolism in diet-induced obesity by improving the adipose tissue phenotype. Adipoq-LPL mice also have increased energy expenditure.

KEYWORDS:

Glucose Metabolism; Insulin Resistance; Lipase; Lipoprotein; Obesity

PMID:
25784555
PMCID:
PMC4416858
DOI:
10.1074/jbc.M114.628487
[Indexed for MEDLINE]
Free PMC Article

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