TRC150094, a novel functional analog of iodothyronines, reduces adiposity by increasing energy expenditure and fatty acid oxidation in rats receiving a high-fat diet.
Chronic overnutrition and modern lifestyles are causing a worldwide epidemic of obesity and associated comorbidities, which is creating a demand to identify underlying biological mechanisms and to devise effective treatments. In rats receiving a high-fat diet (HFD), we analyzed the effects of a 4-wk administration of a novel functional analog of iodothyronines, TRC150094 (TRC). HFD-TRC rats exhibited increased energy expenditure (+24% vs. HFD rats; P<0.05) and body weight (BW) gain comparable to that of standard chow-fed (N) rats [N, HFD, and HFD-TRC rats, +97 g, +140 g (P<0.05 vs. N), and +98 g (P<0.05 vs. HFD)]. HFD-TRC rats had significantly less visceral adipose tissue (vs. HFD rats) and exhibited altered metabolism in two major tissues that are very active metabolically. In liver, mitochondrial fatty acid import and oxidation were increased (+56 and +32%, respectively; P<0.05 vs. HFD rats), and consequently the hepatic triglyceride content was lower (-35%; P<0.05 vs. HFD rats). These effects were independent of the AMP-activated protein kinase-acetyl CoA-carboxylase-malonyl CoA pathway but involved sirtuin 1 activation. In skeletal muscle, TRC induced a fiber shift toward the oxidative type in tibialis anterior muscle, increasing its capacity to oxidize fatty acids. HFD-TRC rats had lower (vs. HFD rats) plasma cholesterol and triglyceride concentrations. If reproduced in humans, these results will open interesting possibilities regarding the counteraction of metabolic dysfunction associated with ectopic/visceral fat accumulation.
Cioffi
Federica
F
Dipartimento di Scienze della Vita, Seconda Universita` di Napoli, Caserta, Italy.
Zambad
Shitalkumar P
SP
Chhipa
Laxmikant
L
Senese
Rosalba
R
Busiello
Rosa Anna
RA
Tuli
Davinder
D
Munshi
Siralee
S
Moreno
Maria
M
Lombardi
Assunta
A
Gupta
Ramesh C
RC
Chauthaiwale
Vijay
V
Dutt
Chaitanya
C
de Lange
Pieter
P
Silvestri
Elena
E
Lanni
Antonia
A
Goglia
Fernando
F
D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D005227:Fatty Acids / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000097:blood / Q000139:chemically induced / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D056564:Sirtuin 1 / Q000378:metabolism; D013970:Thyronines / Q000737:chemistry / Q000494:pharmacology*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D004041:Dietary Fats; D005227:Fatty Acids; D013970:Thyronines; D014280:Triglycerides; D014284:Triiodothyronine; D013972:Thyrotropin; D002334:Carnitine O-Palmitoyltransferase; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D013974:Thyroxine