Effects of gastric bypass surgery on postprandial gut and systemic lipid handling.

BACKGROUND & OBJECTIVES: Obesity is often associated with increased postprandial triglyceride (TG) concentrations, mainly from chylomicrons- and VLDL-TG. These alterations are usually reverted to normal after gastric bypass surgery (GB), through mechanisms which remain unknown. The objective of this study was therefore to assess the contribution of exogenous labelled fatty acids ingested with a meal to postprandial blood chylomicrons and VLDL-TG concentrations after GB. SUBJECTS/METHODS: 7 GB patients 3-5 years after surgery (GB: 2M/5F, mean BMI 30 ± 2 kg/m2, mean age 40 ± 3 years), 6 overweight non operated subjects (OW: 1M/5F, mean BMI 31 ± 3 kg/m2, mean age 38 ± 2 years) and 8 normal weight healthy subjects (NW: 4M/4F, mean BMI 22 ± 1 kg/m2, mean age 26 ± 4 years) were studied over 7 h following ingestion of a liquid meal containing 18 g fat labelled with 250 mg 13C16 palmitate, 22 g protein, 36 g fructose and 36 g glucose. TG, 13C palmitate (13C-palm) and apoB48 concentrations were measured hourly in whole plasma and/or in chylomicrons and VLDL lipoprotein sub-fractions. RESULTS: OW subjects had higher chylomicron-than NW (chylo-TG 96.5 (23.1) vs 28.8 (11.8) mmol/l*420min (p = 0.02)), but similar total, chylo-13C-palm and apoB48 iAUCs. In GB, chylo- 13C-palm and apoB48 increased earlier after meal ingestion, but then remained lower than in NW and OW throughout the postprandial period. GB also had lower chylo-TG iAUCs than OW (8.9 (11.5) vs 96.5 (23.2) mmol/l*420min, p = 0.003). Their apoB48 iAUCs were not different from NW and OW (509.2 (90.5) vs 710.2 (80.5) and 870.1 (297.6) pg/ml*420min, all p > 0.05). CONCLUSIONS: An accelerated postprandial apoB48 rise, together with unchanged postprandial apoB48 iUAC, suggests that intestinal fat absorption and chylomicron secretion was quantitatively unaltered, but accelerated after gastric bypass. In contrast, the decreased postprandial chylo-TG and 13C-palm iAUCs suggest that plasma chylomicron clearance was enhanced after gastric bypass.

The extra-splanchnic fructose escape after ingestion of a fructose-glucose drink: An exploratory study in healthy humans using a dual fructose isotope method.

BACKGROUND & AIMS: The presence of specific fructose transporters and fructose metabolizing enzymes has now been demonstrated in the skeletal muscle, brain, heart, adipose tissue and many other tissues. This suggests that fructose may be directly metabolized and play physiological or pathophysiological roles in extra-splanchnic tissues. Yet, the proportion of ingested fructose reaching the systemic circulation is generally not measured. This study aimed to assess the amount of oral fructose escaping first-pass splanchnic extraction after ingestion of a fructose-glucose drink using a dual oral-intravenous fructose isotope method. METHODS: Nine healthy volunteers were studied over 2 h before and 4 h after ingestion of a drink containing 30.4 ± 1.0 g of glucose (mean ± SEM) and 30.4 ± 1.0 g of fructose labelled with 1% [U-13C6]-fructose. A 75%-unlabeled fructose and 25%-[6,6-2H2]-fructose solution was continuously infused (100 µg kg-1 min-1) over the 6 h period. Total systemic, oral and endogenous fructose fluxes were calculated from plasma fructose concentrations and isotopic enrichments. The fraction of fructose escaping first-pass splanchnic extraction was calculated assuming a complete intestinal absorption of the fructose drink. RESULTS: Fasting plasma fructose concentration before tracer infusion was 17.9 ± 0.6 µmol.L-1. Fasting endogenous fructose production detected by tracer dilution analysis was 55.3 ± 3.8 µg kg-1min-1. Over the 4 h post drink ingestion, 4.4 ± 0.2 g of ingested fructose (i.e. 14.5 ± 0.8%) escaped first-pass splanchnic extraction and reached the systemic circulation. Endogenous fructose production significantly increased to a maximum of 165.4 ± 10.7 µg kg-1·min-1 60 min after drink ingestion (p < 0.001). CONCLUSIONS: These data indicate that a non-negligible fraction of fructose is able to escape splanchnic extraction and circulate in the periphery. The metabolic effects of direct fructose metabolism in extra-splanchnic tissues, and their relationship with metabolic diseases, remain to be evaluated. Our results also open new research perspectives regarding the physiological role of endogenous fructose production.

Endurance Training with or without Glucose-Fructose Ingestion: Effects on Lactate Metabolism Assessed in a Randomized Clinical Trial on Sedentary Men.

Glucose-fructose ingestion increases glucose and lactate oxidation during exercise. We hypothesized that training with glucose-fructose would induce key adaptations in lactate metabolism. Two groups of eight sedentary males were endurance-trained for three weeks while ingesting either glucose-fructose (GF) or water (C). Effects of glucose-fructose on lactate appearance, oxidation, and clearance were measured at rest and during exercise, pre-training, and post-training. Pre-training, resting lactate appearance was 3.6 ± 0.5 vs. 3.6 ± 0.4 mg·kg-1·min-1 in GF and C, and was increased to 11.2 ± 1.4 vs. 8.8 ± 0.7 mg·kg-1·min-1 by exercise (Exercise: p < 0.01). Lactate oxidation represented 20.6% ± 1.0% and 17.5% ± 1.7% of lactate appearance at rest, and 86.3% ± 3.8% and 86.8% ± 6.6% during exercise (Exercise: p < 0.01) in GF and C, respectively. Training with GF increased resting lactate appearance and oxidation (Training × Intervention: both p < 0.05), but not during exercise (Training × Intervention: both p > 0.05). Training with GF and C had similar effects to increase lactate clearance during exercise (+15.5 ± 9.2 and +10.1 ± 5.9 mL·kg-1·min-1; Training: p < 0.01; Training × Intervention: p = 0.97). The findings of this study show that in sedentary participants, glucose-fructose ingestion leads to high systemic lactate appearance, most of which is disposed non-oxidatively at rest and is oxidized during exercise. Training with or without glucose-fructose increases lactate clearance, without altering lactate appearance and oxidation during exercise.

Effects of roux-en-Y gastric bypass surgery on postprandial fructose metabolism.

OBJECTIVE: Fructose is partly metabolized in small bowel enterocytes, where it can be converted into glucose or fatty acids. It was therefore hypothesized that Roux-en-Y gastric bypass (RYGB) may significantly alter fructose metabolism. METHODS: We performed a randomized clinical study in eight patients 12-17 months after RYGB and eight control (Ctrl) subjects. Each participant was studied after ingestion of a protein and lipid meal (PL) and after ingestion of a protein+lipid+fructose+glucose meal labeled with (13) C-fructose (PLFG). Postprandial blood glucose, fructose, lactate, apolipoprotein B48 (apoB48), and triglyceride (TG) concentrations, (13) C-palmitate concentrations in chylomicron-TG and VLDL-TG, fructose oxidation ((13) CO2 production), and gluconeogenesis from fructose (GNGf) were measured over 6 hours. RESULTS: After ingestion of PLFG, postprandial plasma fructose, glucose, insulin, and lactate concentrations increased earlier and reached higher peak values in RYGB than in Ctrl. GNGf was 33% lower in RYGB than Ctrl (P = 0.041), while fructose oxidation was unchanged. Postprandial incremental areas under the curves for total TG and chylomicrons-TG were 72% and 91% lower in RYGB than Ctrl (P = 0.064 and P = 0.024, respectively). ApoB48 and (13) C-palmitate concentrations were not significantly different. CONCLUSIONS: Postprandial fructose metabolism was not grossly altered, but postprandial lipid concentrations were markedly decreased in subjects having had RYGB surgery.

Metabolic fate of fructose ingested with and without glucose in a mixed meal.

Ingestion of pure fructose stimulates de novo lipogenesis and gluconeogenesis. This may however not be relevant to typical nutritional situations, where fructose is invariably ingested with glucose. We therefore assessed the metabolic fate of fructose incorporated in a mixed meal without or with glucose in eight healthy volunteers. Each participant was studied over six hours after the ingestion of liquid meals containing either 13C-labelled fructose, unlabeled glucose, lipids and protein (Fr + G) or 13C-labelled fructose, lipids and protein, but without glucose (Fr), or protein and lipids alone (ProLip). After Fr + G, plasma 13C-glucose production accounted for 19.0% ± 1.5% and 13CO2 production for 32.2% ± 1.3% of 13C-fructose carbons. After Fr, 13C-glucose production (26.5% ± 1.4%) and 13CO2 production (36.6% ± 1.9%) were higher (p < 0.05) than with Fr + G. 13C-lactate concentration and very low density lipoprotein VLDL 13C-palmitate concentrations increased to the same extent with Fr + G and Fr, while chylomicron 13C-palmitate tended to increase more with Fr + G. These data indicate that gluconeogenesis, lactic acid production and both intestinal and hepatic de novo lipogenesis contributed to the disposal of fructose carbons ingested together with a mixed meal. Co-ingestion of glucose decreased fructose oxidation and gluconeogenesis and tended to increase 13C-pamitate concentration in gut-derived chylomicrons, but not in hepatic-borne VLDL-triacylglycerol (TG). This trial was approved by clinicaltrial. gov. Identifier is NCT01792089.

Metabolic effects of mental stress during over- and underfeeding in healthy women.

OBJECTIVE: To assess the short-term consequences of carbohydrate or fat overfeeding or of food restriction on the metabolic effects of mental stress in healthy lean women. RESEARCH METHODS AND PROCEDURES: The effects of a sympathetic activation elicited by mental stress were evaluated in a group of healthy women after standardized isocaloric feeding (ISO) or after a 3-day overfeeding with 40% excess calories as either carbohydrate overfeeding (CHO OF) or fat overfeeding (FAT OF). Oxygen consumption rate (VO(2)) was measured as an index of energy expenditure, and subcutaneous glycerol concentrations were monitored with microdialysis. The same measurements were performed in another group of healthy women after ISO and after a 3-day period of underfeeding with a protein sparing modified fast (UF). RESULTS: In all conditions, mental stress significantly increased heart rate, blood pressure, plasma norepinephrine and epinephrine concentrations, and VO(2), and produced a nonsignificant increase in subcutaneous glycerol concentrations. CHO OF and FAT OF did not alter the effects of mental stress on VO(2) and subcutaneous glycerol concentrations. In contrast, UF increased basal VO(2) but significantly reduced its stimulation by mental stress. UF also enhanced the increase in subcutaneous glycerol concentrations during mental stress. DISCUSSION: UF reduces the stimulation of energy expenditure and enhances lipolysis during sympathetic activation. These adaptations may be involved in mobilization of endogenous fat while limiting weight loss. In contrast, short-term overfeeding fails to alter the sympathetic control of energy expenditure and lipolysis.

Effect of carbohydrate overfeeding on whole body and adipose tissue metabolism in humans.

OBJECTIVE: To evaluate the effect of a 4-day carbohydrate overfeeding on whole body net de novo lipogenesis and on markers of de novo lipogenesis in subcutaneous adipose tissue of healthy lean humans. RESEARCH METHODS AND PROCEDURES: Nine healthy lean volunteers (five men and four women) were studied after 4 days of either isocaloric feeding or carbohydrate overfeeding. On each occasion, they underwent a metabolic study during which their energy expenditure and net substrate oxidation rates (indirect calorimetry), and the fractional activity of the pentose-phosphate pathway in subcutaneous adipose tissue (subcutaneous microdialysis with 1,6(13)C2,6,6(2)H2 glucose) were assessed before and after administration of glucose. Adipose tissue biopsies were obtained at the end of the experiments to monitor mRNAs of key lipogenic enzymes. RESULTS: Carbohydrate overfeeding increased basal and postglucose energy expenditure and net carbohydrate oxidation. Whole body net de novo lipogenesis after glucose loading was markedly increased at the expense of glycogen synthesis. Carbohydrate overfeeding also increased mRNA levels for the key lipogenic enzymes sterol regulatory element-binding protein-1c, acetyl-CoA carboxylase, and fatty acid synthase. The fractional activity of adipose tissue pentose-phosphate pathway was 17% to 22% and was not altered by carbohydrate overfeeding. DISCUSSION: Carbohydrate overfeeding markedly increased net de novo lipogenesis at the expense of glycogen synthesis. An increase in mRNAs coding for key lipogenic enzymes suggests that de novo lipogenesis occurred, at least in part, in adipose tissue. The pentose-phosphate pathway is active in adipose tissue of healthy humans, consistent with an active role of this tissue in de novo lipogenesis.