Prevention of hepatic fatty acids alterations in athymic mice by neonatal thymulin gene therapy

BRAVO MARGARITA GARCIADE; POLO MONICA P.; REGGIANI PAULA C; RIMOLDI OMAR J; GOYA RODOLFO G

Rosario

Congreso; XLII Reunión Anual SAIB; 2006

Sociedad Argentina de Investigaciones Bioquímicas y Biología Molecular

  During adult life athymic (nude) male mice display not only a severe T-cell related immunodeficiency but also endocrine imbalances and a moderate hyperglycemia. We studied the impact of congenital athymia on hepatic lipid composition and also assessed the ability of neonatal thymulin gene therapy to prevent the effects of athymia. We constructed a recombinant adenoviral vector, RAd-metFTS, expressing a synthetic DNA sequence encoding met-FTS, an analog of the thymic peptide Facteur Thymique S¨¦rique (FTS) whose Zn-bound biologically active form is known as thymulin. On postnatal day 1-2 homozygous (nu/nu) nude and heterozygous (nu/+) mice were i.m. injected with 108 pfu of  RAd-metFTS or RAd-¦Âgal (control vector). The animals were processed at 52 days of age. Serum thymulin, hepatic phospholipid 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 hepatic phospholipid (PL) of nu/nu animals as compared to nu/+ counterparts. Some of these alterations, like that in the relative content of 22:6 n-3 in liver PL and the unsaturation index, were completely or partially prevented by neonatal thymulin gene therapy. We conclude that the thymus influences lipid metabolism and that thymulin is involved in this modulatory activity.