PREVENTION OF HEPATIC FATTY ACIDS ALTERATIONS IN ATHYMIC MICE BY NEONATAL THYMULIN GENE THERAPY

BRAVO, M.M.G. DE; POLO MP; REGGIANI PC; RIMOLDI OJ; GOYA RG

Rosario

Congreso; XLII Reunion Anual de la Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular; 2006

Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular

During adult life athymic (nude) male mice display not only a severe T-cell related immunodeficiency but also endocrineimbalances and a moderate hyperglycemia. We studied the impact of congenital athymia on hepatic lipid composition andalso assessed the ability of neonatal thymulin gene therapy to prevent the effects of athymia. We constructed arecombinant adenoviral vector, RAd-metFTS, expressing a synthetic DNA sequence encoding met-FTS, an analog of thethymic peptide Facteur Thymique Serique (FTS) whose Zn-bound biologically active form is known as thymulin. Onpostnatal day 1-2 homozygous (nu/nu) nude and heterozygous (nu/+) mice were i.m. injected with 108 pfu of RAdmetFTSor RAd-Bgal (control vector). The animals were processed at 52 days of age. Serum thymulin, hepaticphospholipid fatty acid composition and free and esterified cholesterol was determined. The relative percentage of 16:0,18:1 n-9 and 18:1 n-7 fatty acids was lower whereas that of 18:0, 20:4 n-6 and 22:6 n-3 acids was higher in hepaticphospholipid (PL) of nu/nu animals as compared to nu/+ counterparts. Some of these alterations, like that in the relativecontent of 22:6 n-3 in liver PL and the unsaturation index, were completely or partially prevented by neonatal thymulingene therapy. We conclude that the thymus influences lipid metabolism and that thymulin is involved in this modulatoryactivity.