RGD Reference Report - Diacylglycerol acyltransferase-1 inhibition enhances intestinal fatty acid oxidation and reduces energy intake in rats. - Rat Genome Database

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Diacylglycerol acyltransferase-1 inhibition enhances intestinal fatty acid oxidation and reduces energy intake in rats.

Authors: Schober, G  Arnold, M  Birtles, S  Buckett, LK  Pacheco-Lopez, G  Turnbull, AV  Langhans, W  Mansouri, A 
Citation: Schober G, etal., J Lipid Res. 2013 May;54(5):1369-84. doi: 10.1194/jlr.M035154. Epub 2013 Feb 28.
RGD ID: 10400846
Pubmed: PMID:23449193   (View Abstract at PubMed)
PMCID: PMC3622331   (View Article at PubMed Central)
DOI: DOI:10.1194/jlr.M035154   (Journal Full-text)

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 beta-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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Dgat1Ratketone body metabolic process  IMP  RGD 
Dgat1Ratpositive regulation of fatty acid oxidation  IMP  RGD 
Dgat1Ratpositive regulation of triglyceride biosynthetic process  IMP  RGD 
Dgat1Ratregulation of eating behavior  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Dgat1  (diacylglycerol O-acyltransferase 1)


Additional Information