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Hepatic and adipose tissue depot-specific changes in lipid metabolism in Late-onset Obese (LOB) rats.

Journal article
Authors Fredrik Frick
Randip Hume
Iain C Robinson
Staffan Edén
Jan Oscarsson
Published in Lipids
Volume 43
Issue 4
Pages 313-24
ISSN 0024-4201
Publication year 2008
Published at Wallenberg Laboratory
Institute of Neuroscience and Physiology, Department of Physiology
Institute of Medicine, Department of Internal Medicine
Pages 313-24
Language en
Links dx.doi.org/10.1007/s11745-008-3164-...
Keywords Adipose Tissue, White, metabolism, Animals, Animals, Genetically Modified, Cholesterol, VLDL, blood, Lipid Metabolism, physiology, Lipolysis, Lipoprotein Lipase, genetics, metabolism, Lipoproteins, VLDL, blood, Liver, metabolism, Male, Obesity, genetics, metabolism, Rats, Triglycerides, blood
Subject categories Medical and Health Sciences, Physiology, Internal medicine

Abstract

Transgenic Late-onset OBesity (LOB) rats slowly develop a male-specific, autosomal dominant, obesity phenotype with a specific increase in peri-renal white adipose tissue (WAT) depot and preserved insulin sensitivity (Bains et al. in Endocrinology 145:2666-2679, 2004). To better understand the remarkable phenotype of these rats, the lipid metabolism was investigated in male LOB and non-transgenic (NT) littermates. Total plasma cholesterol (C) levels were normal but total plasma triacylglycerol (TAG) (2.8-fold) and hepatic TAG content (25%) was elevated in LOB males. Plasma VLDL-C and VLDL-TAG levels were higher while plasma apoB levels were 60% lower in LOB males. Increased hepatic TAG secretion explained the increased VLDL levels in LOB males. The hepatic gene expression of FAS, SCD-1, mitochondrial (mt)GPAT, and DGAT2 was up-regulated in both old obese and young non-obese LOB rats. Lipoprotein lipase (LPL) activity in heart and epididymal white adipose tissue (WAT) was unchanged, while LPL activity was increased in peri-renal WAT (30%) and decreased in soleus muscle (40%). Moreover, FAS, SCD-1 and DGAT2 gene expression was increased in peri-renal, but not in epididymal WAT. Basal lipolysis was reduced or unchanged and beta-adrenergic stimulated lipolysis was reduced in WAT from both old obese and young non-obese LOB rats. To summarize, the obese phenotype of LOB male rats is associated with increased hepatic TAG production and secretion, a shift in LPL activity from skeletal muscle to WAT, reduced lipolytic response in WAT depots and a specific increase in expression of genes responsible for fatty acid and TAG synthesis in the peri-renal depot.

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