3,5-diiodo-L-thyronine powerfully reduces adiposity in rats by increasing the burning of fats.
The effect of thyroid hormones on metabolism has long supported their potential as drugs to stimulate fat reduction, but the concomitant induction of a thyrotoxic state has greatly limited their use. Recent evidence suggests that 3,5-diiodo-L-thyronine (T2), a naturally occurring iodothyronine, stimulates metabolic rate via mechanisms involving the mitochondrial apparatus. We examined whether this effect would result in reduced energy storage. Here, we show that T2 administration to rats receiving a high-fat diet (HFD) reduces both adiposity and body weight gain without inducing thyrotoxicity. Rats receiving HFD + T2 showed (when compared with rats receiving HFD alone) a 13% lower body weight, a 42% higher liver fatty acid oxidation rate, appoximately 50% less fat mass, a complete disappearance of fat from the liver, and significant reductions in the serum triglyceride and cholesterol levels (-52% and -18%, respectively). Thyroid hormones and thyroid-stimulating hormone (TSH) serum levels were not influenced by T2 administration. The biochemical mechanism underlying the effects of T2 on liver metabolism involves the carnitine palmitoyl-transferase system and mitochondrial uncoupling. If the results hold true for humans, pharmacological administration of T2 might serve to counteract the problems associated with overweight, such as accumulation of lipids in liver and serum, without inducing thyrotoxicity. However, the results reported here do not exclude deleterious effects of T2 on a longer time scale as well as do not show that T2 acts in the same way in humans.
Lanni
Antonia
A
Dipartimento di Scienze della Vita, Seconda Università di Napoli, Caserta, Italy. antonia.lanni@unina2.it
Moreno
Maria
M
Lombardi
Assunta
A
de Lange
Pieter
P
Silvestri
Elena
E
Ragni
Maurizio
M
Farina
Paola
P
Baccari
Gabriella Chieffi
GC
Fallahi
Pupah
P
Antonelli
Alessandro
A
Goglia
Fernando
F
D055372:AMP-Activated Protein Kinases; D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats / Q000008:administration & dosage; D004104:Diiodothyronines / Q000494:pharmacology* / Q000627:therapeutic use; D004734:Energy Metabolism / Q000187:drug effects*; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy; D008099:Liver / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D010084:Oxidation-Reduction; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain / Q000187:drug effects
D004041:Dietary Fats; D004104:Diiodothyronines; D005227:Fatty Acids; D009097:Multienzyme Complexes; D014280:Triglycerides; C030103:3,5-diiodothyronine; D002784:Cholesterol; D002334:Carnitine O-Palmitoyltransferase; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases