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TRC150094, a novel functional analog of iodothyronines, reduces adiposity by increasing energy expenditure and fatty acid oxidation in rats receiving a high‐fat diet
Author(s) -
Cioffi Federica,
Zambad Shitalkumar P.,
Chhipa Laxmikant,
Senese Rosalba,
Busiello Rosa Anna,
Tuli Davinder,
Munshi Siralee,
Moreno Maria,
Lombardi Assunta,
Gupta Ramesh C.,
Chauthaiwale Vijay,
Dutt Chaitanya,
Lange Pieter,
Silvestri Elena,
Lanni Antonia,
Goglia Fernando
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-157115
Subject(s) - beta oxidation , energy expenditure , chemistry , endocrinology , medicine , fatty acid , food science , biochemistry
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, F., Zambad, S. P., Chhipa, L., Senese, R., Busiello, R. A., Tuli, D., Munshi, S., Moreno, M., Lombardi, A., Gupta, R. C., Chauthaiwale, V., Dutt, C., de Lange, P., Silvestri, E., Lanni, A., Goglia, F. TRC150094, a novel functional analog of iodothyronines, reduces adiposity by increasing energy expenditure and fatty acid oxidation in rats receiving a high‐fat diet. FASEB J . 24, 3451–3461 (2010). www.fasebj.org