Metabolic Fate of Fructose Ingested with and without Glucose in a Mixed Meal

Abstract

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 Replacing Sugar-Sweetened Beverages with Artificially-Sweetened Beverages in Overweight Subjects with or without Hepatic Steatosis: A Randomized Control Clinical Trial

“…In contrast with early postprandial glucose and insulin responses, plasma TG concentrations increase slowly over several hours [14,23], with a progressive increase between post-breakfast and post-lunch responses [22]. This pattern of TG response was, therefore, adequately assessed by collecting blood samples at two hours intervals.…”

“…Insulin and glucagon were assessed by radioimmunoassay (Millipore, Billerica, MA, USA). Plasma fructose concentrations were measured by gas chromatography-mass spectrometry (GC-MS) as reported elsewhere [14]. …”

Fructose and NAFLD: The Multifaceted Aspects of Fructose Metabolism

“…Second, fructose phosphorylation in the liver consumes adenosine triphosphate (ATP): As phosphorylation by fructokinase is fast and the cleavage reaction by aldolase B relatively slow, an excess of fructose could cause hepatic phosphate deficiency, leading to AMP accumulation with resulting increased uric acid synthesis [7,21]. Uric acid in turn stimulates the production of ROS [22] via the activation of Transforming Growth Factor β and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 ([23].…”

“…Theytaz et al [21] demonstrate an increase in both 13 C-palmitate chylomicron and 13 C-palmitate VLDL-TG concentrations after a 13 C-fructose load in non-obese, young human subjects. This may contribute to the alteration of metabolism and ultimately of liver function [21,52]. …”

The Sweet Path to Metabolic Demise: Fructose and Lipid Synthesis

“…Additional studies have been conducted to determine whether commonly ingested amounts of fructose or sucrose can acutely regulate pathophysiological processes implicated in the development of metabolic disease and cardiac risk factors. Theytaz and colleagues gave non-obese, young human subjects a single meal that contained ~30gm of fructose (or ~7.5% of a daily caloric requirement) and demonstrated increases in both chylomicron and VLDL triglyceride concentrations several hours after the test meal [14]. Thus, fructose exposures that better mirror typical consumption still promote lipogenesis and hyperlipidemia.…”