Hepatic and adipose tissue depot-specific changes in lipid metabolism in Late-onset Obese (LOB) rats.
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.
Frick
Fredrik
F
Department of Bioscience, AstraZeneca R&D, Pepparedsleden 1, 431 83, Mölndal, Sweden. Fredrik.Frick@astrazeneca.com
Hume
Randip
R
Robinson
Iain C
IC
Edén
Staffan
S
Oscarsson
Jan
J
D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D015243:Cholesterol, VLDL / Q000097:blood; D050356:Lipid Metabolism / Q000502:physiology*; D008066:Lipolysis; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D014280:Triglycerides / Q000097:blood
D015243:Cholesterol, VLDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D008071:Lipoprotein Lipase