Metabolism of sugars: A window to the regulation of glucose and lipid homeostasis by splanchnic organs.

Dietary sugars are absorbed in the hepatic portal circulation as glucose, fructose, or galactose. The gut and liver are required to process fructose and galactose into glucose, lactate, and fatty acids. A high sugar intake may favor the development of cardio-metabolic diseases by inducing Insulin resistance and increased concentrations of triglyceride-rich lipoproteins. A narrative review of the literature regarding the metabolic effects of fructose-containing sugars. Sugars' metabolic effects differ from those of starch mainly due to the fructose component of sucrose. Fructose is metabolized in a set of fructolytic cells, which comprise small bowel enterocytes, hepatocytes, and kidney proximal tubule cells. Compared to glucose, fructose is readily metabolized in an insulin-independent way, even in subjects with diabetes mellitus, and produces minor increases in glycemia. It can be efficiently used for energy production, including during exercise. Unlike commonly thought, fructose when ingested in small amounts is mainly metabolized to glucose and organic acids in the gut, and this organ may thus shield the liver from potentially deleterious effects. The metabolic functions of splanchnic organs must be performed with homeostatic constraints to avoid exaggerated blood glucose and lipid concentrations, and thus to prevent cellular damages leading to non-communicable diseases. Excess fructose intake can impair insulin-induced suppression of glucose production, stimulate de novo lipogenesis, and increase intrahepatic and blood triglyceride concentrations. With chronically high fructose intake, enterocyte can switch to lipid synthesis and accumulation of triglyceride, possibly causing an enterocyte dysfunction

Health effects of fructose and fructose-containing caloric sweeteners: where do we stand 10 years after the initial whistle blowings?

Suspicion that fructose-containing caloric sweeteners (FCCS) may play a causal role in the development of metabolic diseases has elicited intense basic and clinical research over the past 10 years. Prospective cohort studies converge to indicate that FCCS, and more specifically sugar-sweetened beverages (SSBs), consumption is associated with weight gain over time. Intervention studies in which FCCS or SSB consumption is altered while food intake is otherwise left ad libitum indicate that increased FCCS generally increases total energy intake and body weight, while FCCS reduction decreases body weight gain. Clinical trials assessing the effects of SSB reduction as a sole intervention however fail to observe clinically significant weight loss. Many mechanistic studies indicate that excess FCCS can cause potential adverse metabolic effects. Whether this is associated with a long-term risk remains unknown. Scientific evidence that excess FCCS intake causes more deleterious effects to health than excess of other macronutrients is presently lacking. However, the large consumption of FCCS in the population makes it one out of several targets for the treatment and prevention of metabolic diseases

Fructose toxicity: is the science ready for public health actions?

PURPOSE OF REVIEW: The assumption that fructose may be toxic and involved in the pathogenesis of noncommunicable diseases such as obesity, diabetes mellitus, dyslipidemia, and even cancer has resulted in the call for public health action, such as introducing taxes on sweetened beverages. This review evaluates the scientific basis for such action. RECENT FINDINGS: Although some studies hint towards some potential adverse effects of excessive fructose consumption especially when combined with excess energy intake, the results from clinical trials do not support a significant detrimental effect of fructose on metabolic health when consumed as part of a weight-maintaining diet in amounts consistent with the average-estimated fructose consumption in Western countries. However, definitive studies are missing. SUMMARY: Public health policies to eliminate or limit fructose in the diet should be considered premature. Instead, efforts should be made to promote a healthy lifestyle that includes physical activity and nutritious foods while avoiding intake of excess calories until solid evidence to support action against fructose is available. Public health is almost certainly to benefit more from policies that are aimed at promoting what is known to be good than from policies that are prohibiting what is not (yet) known to be bad

Energy expenditure, physical activity and body-weight control

Regular physical exercise and endurance training are associated with low body weight and low body fat mass. The relationship between exercise and body-weight control is complex and incompletely understood. Regular exercise may decrease energy balance through an increase in energy expenditure or an increase in fat oxidation. It may also contribute to weight loss by modulating nutrient intake. An intriguing question that remains unresolved is whether changes in nutrient intake or body composition secondarily affect spontaneous physical activity. If this were the case, physical activity would represent a major adaptative mechanism for body-weight contro

Misconceptions about fructose-containing sugars and their role in the obesity epidemic.

A causal role of fructose intake in the aetiology of the global obesity epidemic has been proposed in recent years. This proposition, however, rests on controversial interpretations of two distinct lines of research. On one hand, in mechanistic intervention studies, detrimental metabolic effects have been observed after excessive isolated fructose intakes in animals and human subjects. On the other hand, food disappearance data indicate that fructose consumption from added sugars has increased over the past decades and paralleled the increase in obesity. Both lines of research are presently insufficient to demonstrate a causal role of fructose in metabolic diseases, however. Most mechanistic intervention studies were performed on subjects fed large amounts of pure fructose, while fructose is ordinarily ingested together with glucose. The use of food disappearance data does not accurately reflect food consumption, and hence cannot be used as evidence of a causal link between fructose intake and obesity. Based on a thorough review of the literature, we demonstrate that fructose, as commonly consumed in mixed carbohydrate sources, does not exert specific metabolic effects that can account for an increase in body weight. Consequently, public health recommendations and policies aiming at reducing fructose consumption only, without additional diet and lifestyle targets, would be disputable and impractical. Although the available evidence indicates that the consumption of sugar-sweetened beverages is associated with body-weight gain, and it may be that fructose is among the main constituents of these beverages, energy overconsumption is much more important to consider in terms of the obesity epidemic

Suppression of alcohol-induced hypertension by dexamethasone

BACKGROUND. Alcohol consumption is associated with an increased incidence of hypertension and stroke, but the triggering mechanisms are unclear. In animals, alcohol causes activation of the sympathetic nervous system and also stimulates the release of corticotropin-releasing hormone (CRH), which has sympatho-excitatory effects when administered centrally. METHODS. To determine whether alcohol evokes sympathetic activation and whether such activation is attenuated by the inhibition of CRH release, we measured blood pressure, heart rate, and sympathetic-nerve action potentials (using intraneural microelectrodes) in nine normal subjects before and during an intravenous infusion of alcohol (0.5 g per kilogram of body weight over a period of 45 minutes) and for 75 minutes after the infusion. Each subject received two infusions, one after the administration of dexamethasone (2 mg per day) and one after the administration of a placebo for 48 hours. RESULTS. The infusion of alcohol alone evoked a marked (P < 0.001) and progressive increase in the mean (+/- SD) rate of sympathetic discharge, from 16 +/- 3 bursts per minute at base line to 30 +/- 8 bursts per minute at the end of the two-hour period. This sympathetic activation was accompanied during the second hour by an increase in mean arterial pressure of 10 +/- 5 mm Hg (P < 0.001). After the administration of dexamethasone, the alcohol infusion had no detectable sympathetic effect. The dexamethasone-induced suppression of sympathetic activation was associated with a decrease in mean arterial pressure of 7 +/- 6 mm Hg (P < 0.001) during the alcohol infusion and with suppression of the pressor effect during the second hour. CONCLUSIONS. Alcohol induces pressor effects by sympathetic activation that appear to be centrally mediated. It is possible that these alcohol-induced hemodynamic and sympathetic actions could participate in triggering cardiovascular events

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

Energy expenditure, physical activity and body-weight control

Regular physical exercise and endurance training are associated with low body weight and low body fat mass. The relationship between exercise and body-weight control is complex and incompletely understood. Regular exercise may decrease energy balance through an increase in energy expenditure or an increase in fat oxidation. It may also contribute to weight loss by modulating nutrient intake. An intriguing question that remains unresolved is whether changes in nutrient intake or body composition secondarily affect spontaneous physical activity. If this were the case, physical activity would represent a major adaptative mechanism for body-weight control