High expression of thyroid hormone receptors and mitochondrial glycerol-3-phosphate dehydrogenase in the liver is linked to enhanced fatty acid oxidation in Lou/C, a rat strain resistant to obesity.
Besides its well recognized role in lipid and carbohydrate metabolisms, glycerol is involved in the regulation of cellular energy homeostasis via glycerol-3-phosphate, a key metabolite in the translocation of reducing power across the mitochondrial inner membrane with mitochondrial glycerol-3-phosphate dehydrogenase. Here, we report a high rate of gluconeogenesis from glycerol and fatty acid oxidation in hepatocytes from Lou/C, a peculiar rat strain derived from Wistar, which is resistant to age- and diet-related obesity. This feature, associated with elevated cellular respiration and cytosolic ATP/ADP and NAD(+)/NADH ratios, was linked to a high expression and activity of mitochondrial glycerol-3-phosphate dehydrogenase. Interestingly, this strain exhibited high expression and protein content of thyroid hormone receptor, whereas circulating thyroid hormone levels were slightly decreased and hepatic thyroid hormone carrier MCT-8 mRNA levels were not modified. We propose that an enhanced liver thyroid hormone receptor in Lou/C may explain its unique resistance to obesity by increasing fatty acid oxidation and lowering liver oxidative phosphorylation stoichiometry at the translocation of reducing power into mitochondria.
Taleux
Nellie
N
Bioénergétique Fondamentale et Appliquée INSERM-U884, Université J. Fourier, Grenoble Cedex 9, France.
Guigas
Bruno
B
Dubouchaud
Hervé
H
Moreno
Maria
M
Weitzel
Joachim M
JM
Goglia
Fernando
F
Favier
Roland
R
Leverve
Xavier M
XM
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D005943:Gluconeogenesis / Q000502:physiology; D005990:Glycerol / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism*; D005994:Glycerophosphates / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D027501:Monocarboxylic Acid Transporters; D009243:NAD / Q000378:metabolism; D009765:Obesity; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D013045:Species Specificity
D005227:Fatty Acids; D005994:Glycerophosphates; D027501:Monocarboxylic Acid Transporters; D011988:Receptors, Thyroid Hormone; C478998:monocarboxylate transporter 8, rat; D009243:NAD; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005993:Glycerolphosphate Dehydrogenase; D005990:Glycerol