title: TRC150094, a novel functional analog of iodothyronines, reduces adiposity by increasing energy expenditure and fatty acid oxidation in rats receiving a high-fat diet.
abstract: 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.
authors.affiliation: Dipartimento di Scienze della Vita, Seconda Universita` di Napoli, Caserta, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cioffi
authors.forename: Shitalkumar P
authors.initials: SP
authors.lastname: Zambad
authors.forename: Laxmikant
authors.initials: L
authors.lastname: Chhipa
authors.forename: Rosalba
authors.initials: R
authors.lastname: Senese
authors.forename: Rosa Anna
authors.initials: RA
authors.lastname: Busiello
authors.forename: Davinder
authors.initials: D
authors.lastname: Tuli
authors.forename: Siralee
authors.initials: S
authors.lastname: Munshi
authors.forename: Maria
authors.initials: M
authors.lastname: Moreno
authors.forename: Assunta
authors.initials: A
authors.lastname: Lombardi
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
authors.forename: Vijay
authors.initials: V
authors.lastname: Chauthaiwale
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Dutt
authors.forename: Pieter
authors.initials: P
authors.lastname: de Lange
authors.forename: Elena
authors.initials: E
authors.lastname: Silvestri
authors.forename: Antonia
authors.initials: A
authors.lastname: Lanni
authors.forename: Fernando
authors.initials: F
authors.lastname: Goglia
mesh_terms: 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
chemical_list: 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