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Por favor, use este identificador para citar o enlazar este ítem: http://hdl.handle.net/20.500.12222/35
Título : Diacylglycerol acyltransferase 1 inhibition enhances intestinal fatty acid oxidation and reduces energy intake in rats
Autor(es) : Gustavo Pacheco-Lopez, 0000-0002-3458-197X
Autor(es) sin ID: Schober, Gundrun; Arnold, Myrtha; Birtles, Susan; Buckett;, Linda K.; Turnbull, Andrew V.; Langhans, Wolfgang; Mansouri, Abdelhak
Fecha de publicación : 2013
Tipo de resultado Científico: preprint
Materia o Disciplina: MEDICINA Y CIENCIAS DE LA SALUD
Palabras clave: Triacilglicerol;; Cetogénesis;; Intestino delgado;; Enterocitos;; Dieta rica en grasas;; Alimentación;; Acil CoA:; Diacilglicerol aciltransferasa-1Triacylglycerol;; Ketogenesis;; Acyl CoA iacylglycerol acyltransferase-1; Small intestine;; Enterocytes;; Hi
Descripción : Acyl CoA: diacylglycerol acyltransferase-1 (DGAT-1) catalyzes the final step in triacylglycerol (TAG) synthesis and is highly expressed in the small intestine. Because DGAT-1 knockout mice are resistant to diet-induced obesity, we investigated the acute effects of intragastric (IG) infusion of a small molecule diacylglycerol acyltransferase-1 inhibitor (DGAT-1i) on eating, circulating fat metabolites, indirect calorimetry, and hepatic and intestinal expression of key fat catabolism enzymes in male rats adapted to an 8 h feeding-16 h deprivation schedule. Also, the DGAT-1i effect on fatty acid oxidation (FAO) was investigated in enterocyte cell culture models. IG DGAT-1i infusions reduced energy intake compared with vehicle in high-fat diet (HFD)-fed rats, but scarcely in chow-fed rats. IG DGAT-1i also blunted the postprandial increase in serum TAG and increased β-hydroxybutyrate levels only in HFD-fed rats, in which it lowered the respiratory quotient and increased intestinal, but not hepatic, protein levels of Complex III of the mitochondrial respiratory chain and of mitochondrial hydroxymethylglutaryl-CoA synthase. Finally, the DGAT-1i enhanced FAO in CaCo2 (EC50 = 0.3494) and HuTu80 (EC50 = 0.00762) cells. Thus, pharmacological DGAT-1 inhibition leads to an increase in intestinal FAO and ketogenesis when dietary fat is available. This may contribute to the observed eating-inhibitory effect.
Editor: Universidad Autónoma Metropolitana. Unidad Lerma
URI : http://hdl.handle.net/20.500.12222/35
Condiciones de licencia: http://creativecommons.org/licenses/by-nc-nd/4.0/
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