title: Increasing adipocyte lipoprotein lipase improves glucose metabolism in high fat diet-induced obesity.
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.
authors.affiliation: From the Department of Medicine, Division of Endocrinology, Barnstable Brown Diabetes and Obesity Center.
authors.forename: R Grace
authors.initials: RG
authors.lastname: Walton
authors.affiliation: From the Department of Medicine, Division of Endocrinology, Barnstable Brown Diabetes and Obesity Center.
authors.forename: Beibei
authors.initials: B
authors.lastname: Zhu
authors.affiliation: the Department of Molecular Biology and Genetics, Faculty of Life Sciences, Mugla Sitki Kocman University, 48000 Mugla, Turkey.
authors.forename: Resat
authors.initials: R
authors.lastname: Unal
authors.affiliation: From the Department of Medicine, Division of Endocrinology, Barnstable Brown Diabetes and Obesity Center.
authors.forename: Michael
authors.initials: M
authors.lastname: Spencer
authors.affiliation: Division of Cardiovascular Medicine.
authors.forename: Manjula
authors.initials: M
authors.lastname: Sunkara
authors.affiliation: Division of Cardiovascular Medicine.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Morris
authors.affiliation: Department of Biostatistics, College of Public Health.
authors.forename: Richard
authors.initials: R
authors.lastname: Charnigo
authors.affiliation: Department of Pharmacology and Nutritional Sciences, and.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Katz
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky 40536 and.
authors.forename: Alan
authors.initials: A
authors.lastname: Daugherty
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky 40536 and.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Howatt
authors.affiliation: From the Department of Medicine, Division of Endocrinology, Barnstable Brown Diabetes and Obesity Center.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Kern
authors.affiliation: From the Department of Medicine, Division of Endocrinology, Barnstable Brown Diabetes and Obesity Center, bfinlin@uky.edu.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Finlin
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione; D008071:Lipoprotein Lipase; D005947:Glucose
keywords: Glucose Metabolism; Insulin Resistance; Lipase; Lipoprotein; Obesity