Cellular Mechanisms Underlying the Protective Effects of Preoperative Feeding

Abstract

To investigate the effects of preoperative feeding with a carbohydrate-based drink that also contained glutamine and antioxidants (oral nutritional supplement [ONS], Fresenuis Kabi, Germany) on glycogen reserves, mitochondrial function, and the expression of key metabolic genes and proteins. Preoperative carbohydrate loading attenuates the decline in postoperative insulin sensitivity but the cellular mechanisms underlying this remain unclear. Two groups of 20 patients undergoing laparoscopic cholecystectomy participated in this randomized placebo-controlled double-blind study. Patients received either 600 mL of ONS or placebo the evening before surgery, and again 300 mL 3 to 4 hours before anesthesia. A 300-mL aliquot of ONS contained 50 g of carbohydrate, 15 g of glutamine and antioxidants. Blood was sampled before ingestion of the evening drink, after induction of anesthesia, and on postoperative day 1 for measurement of concentrations of glucose, glutamine, and antioxidants. Rectus abdominis muscle and liver biopsies were performed intraoperatively to determine glycogen and glutamine concentrations, mitochondrial function, pyruvate dehydrogenase kinase (PDK4), forkhead transcription factor 1 (FOXO1), and metallothionein 1A (Mt1A) expression. There were no drink-related complications. ONS ingestion led to increased intraoperative liver glycogen reserves (44%, P < 0.001) and plasma glutamine and antioxidant concentrations, the latter 2 remaining elevated up to the first postoperative day. Muscle PDK4 mRNA, PDK4 protein expression, and Mt1A mRNA expression were 4-fold (P < 0.001), 44% (P < 0.05), and 1.5-fold (P < 0.001), respectively, lower in the ONS group. There were no differences in FOXO1 mRNA and protein expression. The changes in muscle PDK4 may explain the mechanism by which preoperative feeding with carbohydrate-based drinks attenuates the development of postoperative insulin resistance.