Comparative effects of 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) and 3,5-diiodo-3'-isopropylthyroacetic acid (IpTA2) on body weight gain and lipid metabolism in genetically obese Zucker rats.
3,5-Dimethyl-3'-isopropyl-L-thyronine (DIMIT) and 3,5-diiodo-3'-isopropylthyroacetic acid (IpTA2), two thyroid hormone analogs, have been tested in genetically obese Zucker rats and their lean littermates, in comparison with thyroxine (T4) and triiodothyronine (T3) for their thyromimetic activities on body weight gain and lipid levels in serum and liver. The compounds were administered for 9 weeks by orogastric tube to 6- to 8-week-old animals. While body weight gain remained practically unchanged in the lean rats, it decreased significantly in the obese individuals, especially with IpTA2. The serum lipid concentrations were also decreased in the obese rats in comparison with their lean littermates, especially with DIMIT. The connection observed between the structure of DIMIT and IpTA2 on one hand and their effects on the other is in good agreement with previous studies. Our results confirm that the iodine substituents are not necessary for thyromimetic activity and demonstrate that the isopropyl substituent in 3' plays an important role in the serum lipid-lowering effect of the thyroid hormone analogs tested.
Loireau
A
A
Autissier
N
N
Dumas
P
P
Michel
O
O
Jorgensen
E C
EC
Michel
R
R
D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D012321:DNA-Directed RNA Polymerases / Q000032:analysis; D005260:Female; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D013329:Structure-Activity Relationship; D013970:Thyronines / Q000494:pharmacology*; D013974:Thyroxine / Q000494:pharmacology; D014284:Triiodothyronine / Q000031:analogs & derivatives / Q000494:pharmacology
D013970:Thyronines; D014284:Triiodothyronine; C022861:3,5-dimethyl-3'-isopropyl-L-thyronine; C010642:3,3',5-triiodothyroacetic acid; D012321:DNA-Directed RNA Polymerases; D013974:Thyroxine