RESUMO
OBJECTIVE: The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults. DESIGN: To investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults. RESULTS: Propionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10â g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24â weeks, 10â g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group. CONCLUSIONS: These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans. TRIAL REGISTRATION NUMBER: NCT00750438.
Assuntos
Adiposidade/efeitos dos fármacos , Regulação do Apetite/efeitos dos fármacos , Manutenção do Peso Corporal/efeitos dos fármacos , Colo/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Sobrepeso/tratamento farmacológico , Peptídeo YY/metabolismo , Propionatos/administração & dosagem , Células Cultivadas , Colo/citologia , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Propionatos/farmacologiaRESUMO
[reaction: see text] Asymmetric reduction of ketimines 1 with trichlorosilane can be catalyzed by a new N-methyl L-valine derived Lewis basic organocatalyst, such as 4d, with high enantioselectivity. The structure-reactivity investigation suggests hydrogen bonding and arene-arene interactions between the catalyst and the incoming imine as the main factor determining the enantiofacial selectivity.