Leucine (and lysine) increased plasma levels of the satiety hormone cholecystokinin (CCK), and phenylalanine of the incretin glucagon-like peptide 1 (GLP-1) after oral gavages in pigs

Abstract

Abstract Excess dietary amino acids (AA) has been associated with reduced feed intake, increased satiation, and extended satiety in pigs. Recent ex vivo studies suggested that satiety peptide cholecystokinin (CCK) and insulinotropic glucagon-like peptide 1 (GLP-1), mediated the anorexigenic or insulinotropic effects of Lys, Glu, Phe, Ile, and Leu. However, the ex vivo model limitations require validation in vivo. The aim of the present study was to assess the effect of orally administered AA in vivo in pigs. It was hypothesized that oral Lys, Ile, and Leu have an anorexigenic effect via CCK, while Glu and Phe have an insulinotropic effect increasing circulating levels of GLP-1. Eight entire male pigs (Landrace × Large White) of 18.23 ± 1.06 kg of body weight were administered an oral gavage of water (control) or a 3 mmol/kg of Glu, Ile, Leu, Lys, Phe, or glucose (positive control for GLP-1 release) following an overnight fasting during 5 consecutive days using an incomplete latin square design. Blood samples were collected from the jugular vein before (−5 min, baseline value) and after the gavage (5, 15, 30, 60 and 90 min) to assess CCK and GLP-1 plasma levels. Pigs administered the oral gavage of Leu (P < 0.05), or Lys (P < 0.1) had increased levels of plasma CCK from 0 to 90 min post-gavage when compared to the control. A strong association (P < 0.001) was observed between GLP-1 plasma levels with Phe intake. The impact was significant starting 30 min post-gavage and was sustained until the end of the experiment (90 min post-gavage). Glucose administration increased GLP-1 early after the intake at the 5 min mark (P < 0.1). A positive correlation (P < 0.05, r = 0.89) driven by the impact of Phe at the 60 to 90 min post-gavage was identified between CCK and GLP-1 indicating feedback mechanisms between proximal and distal small intestine. In conclusion, oral gavages of Leu and Lys increased anorexigenic hormone CCK plasma levels in pigs. Phe caused a significant long-lasting increase in incretin GLP-1 plasma levels. Blood CCK and GLP-1 concentrations in Phe gavaged pigs were positively correlated indicating a potential feedback mechanism between proximal (CCK) and distal (GLP-1) small intestine. The present results are compatible with the known anorexigenic effects of excess dietary Leu and Lys, and the insulinotropic effect of Phe in pigs. These results demonstrate the relevance of accurate feed formulation practices particularly in post weaning pigs.