Intraduodenal infusion of alpha-ketoglutarate decreases whole body energy expenditure in growing pigs

BACKGROUND AND AIMS: alpha-Ketoglutarate (AKG) has been suggested to play a particular role as an oxidative fuel for the gut, and thus may have a sparing function for fuels such as glutamate and aspartate. Using the pig model we aimed to quantify how the route of administration (intravenous, i.v.; intragastric, i.g.; intraduodenal, i.d.) affects AKG utilization, whole body energy expenditure (EE) and nutrient oxidation. METHODS: Pigs (15 kg) were supplied with a complete nutrient solution (NS) via catheters. To explore the metabolic effects of AKG, 1.0 g AKG kgBW(-1)d(-1) was infused simultaneously with the NS using either the i.d., i.v. or i.g. route. [1-(13)C]AKG (15 mg kgBW(-1)) was infused i.d., i.v. or i.g., respectively, for 3h. AKG utilization (AKG UTIL) was estimated as AKG UTIL=100-(13)C recovery (% of (13)C dose). (13)C recovery was calculated from the (13)C enrichment in breath CO(2) and the whole-body CO(2) production. RESULTS: AKG infusion and NS via the i.d. route resulted in a reduced AKG UTIL (40.1+/-6.7) as compared to the i.v. route (62.9+/-2.4, P<0.001) and i.g. route (62.3+/-1.6, P<0.001). The total EE was lower with the i.d. route of AKG and NS (745+/-68 kJkgBW(-0.62)d(-1)) as compared to the i.v. route (965+/-54 kJkgBW(-0.62)d(-1), P<0.005) and i.g. route (918+/-43 kJkgBW(-0.62)d(-1), P<0.005). Carbohydrate oxidation was increased with the i.d. route (38.2g+/-3.4 kgBW(-0.62)d(-1)) as compared to the i.v. route (27.8+/-2.9 gkgBW(-0.62)d(-1), P<0.08) and i.g. route (23.9+/-8.5 gkgBW(-0.62)d(-1), P<0.05). Fat oxidation was decreased (2.1+/-1.9 gkgBW(-0.62)d(-1); P<0.001) with the i.d. route as compared to the i.v. route (11.5+/-1.4 gkgBW(-0.62)d(-1), P<0.001) and i.g. route (11.9+/-3.1 gkgBW(-0.62)d(-1), P<0.001). CONCLUSIONS: The i.d. infusion of AKG in combination with the NS affected the whole body EE and nutrient oxidation, in comparison to that obtained with the i.v. and i.g. routes. It was concluded that the i.d. administration of AKG markedly controlled the nutrient partitioning in the oxidation processes. Finally, in contrary to the observations with glutamine or glutamate, a considerable percentage of the AKG infusion was retained in the body irrespective of the route of administration.