Fructose References

Human studies support the relationship between high intake of fructose-sweetened beverages and type 2 diabetes, but there is a debate on whether this effect is fructose-specific or it is merely associated to an excessive caloric intake. Here we investigate the effects of 2 months’ supplementation to female rats of equicaloric 10% w/v fructose or glucose solutions on insulin sensitivity in target tissues. Fructose supplementation caused hepatic deposition of triglycerides and changed the fatty acid profile of this fraction, with an increase in monounsaturated and a decrease in polyunsaturated species, but did not cause inflammation and oxidative stress. Fructose but not glucose-supplemented rats displayed an abnormal glucose tolerance test, and did not show increased phosphorylation of V-akt murine thymoma viral oncogene homolog-2 (Akt) in white adipose tissue and liver after insulin administration. In skeletal muscle, phosphorylation of Akt and of Akt substrate of 160 kDA (AS160) was not impaired but the expression of the glucose transporter type 4 (GLUT4) in the plasma membrane was reduced only in fructose-fed rats. In conclusion, fructose but not glucose supplementation causes fatty liver without inflammation and oxidative stress and impairs insulin signaling in the three major insulin-responsive tissues independently from the increase in energy intake.

Baena M1,2, Sangüesa G1,2, Dávalos A3, Latasa MJ3, Sala-Vila A4,5, Sánchez RM1,2,4, Roglans N1,2,4, Laguna JC1,2,4, Alegret M1,2,4.

Recent evidence suggests that fructose consumption is associated with weight gain, fat deposition and impaired cognitive function. However it is unclear whether the detrimental effects are caused by fructose itself or by the concurrent increase in overall energy intake. In the present study we examine the impact of a fructose diet relative to an isocaloric glucose diet in the absence of overfeeding, using a mouse model that mimics fructose intake in the top percentile of the USA population (18% energy). Following 77 days of supplementation, changes in body weight (BW), body fat, physical activity, cognitive performance and adult hippocampal neurogenesis were assessed. Despite the fact that no differences in calorie intake were observed between groups, the fructose animals displayed significantly increased BW, liver mass and fat mass in comparison to the glucose group. This was further accompanied by a significant reduction in physical activity in the fructose animals. Conversely, no differences were detected in hippocampal neurogenesis and cognitive/motor performance as measured by object recognition, fear conditioning and rotorod tasks. The present study suggests that fructose per se, in the absence of excess energy intake, increases fat deposition and BW potentially by reducing physical activity, without impacting hippocampal neurogenesis or cognitive function.

Rendeiro C1, Masnik AM2, Mun JG3, Du K3, Clark D4, Dilger RN5, Dilger AC6, Rhodes JS7.
Author information
11] Beckman Institute for Advanced Science and Technology, 405 N. Mathews Ave., Urbana, IL 61801 [2] Center for Nutrition, Learning and Memory, University of Illinois at Urbana-Champaign.
21] Beckman Institute for Advanced Science and Technology, 405 N. Mathews Ave., Urbana, IL 61801 [2] Center for Nutrition, Learning and Memory, University of Illinois at Urbana-Champaign [3] Department of Psychology, University of Illinois at Urbana-Champaign.
31] Beckman Institute for Advanced Science and Technology, 405 N. Mathews Ave., Urbana, IL 61801 [2] Center for Nutrition, Learning and Memory, University of Illinois at Urbana-Champaign [3] Division of Nutritional Sciences, University of Illinois at Urbana-Champaign.
4Department of Animal Sciences, University of Illinois at Urbana-Champaign.
51] Beckman Institute for Advanced Science and Technology, 405 N. Mathews Ave., Urbana, IL 61801 [2] Division of Nutritional Sciences, University of Illinois at Urbana-Champaign [3] Department of Animal Sciences, University of Illinois at Urbana-Champaign.
6Division of Nutritional Sciences, University of Illinois at Urbana-Champaign.
71] Beckman Institute for Advanced Science and Technology, 405 N. Mathews Ave., Urbana, IL 61801 [2] Center for Nutrition, Learning and Memory, University of Illinois at Urbana-Champaign [3] Department of Psychology, University of Illinois at Urbana-Champaign [4] Division of Nutritional Sciences, University of Illinois at Urbana-Champaign.
Sci Rep. 2015 Apr 20;5:9589. doi: 10.1038/srep09589.

Abstract
CONTEXT:
Consumption of high-fructose diets promotes hepatic fatty acid synthesis (de novo lipogenesis [DNL]) and an atherogenic lipid profile. It is unclear if these effects occur independent of positive energy balance and weight gain.
OBJECTIVES:
We compared the effects of a high-fructose (25% of energy content) weight-maintaining diet to those of an isocaloric diet with the same macronutrient distribution but in which complex carbohydrate (CCHO) was substituted for fructose.
DESIGN, SETTING AND PARTICIPANTS:
Eight healthy men were studied as inpatients for consecutive nine-day periods. Stable isotope tracers were used to measure fractional hepatic DNL and endogenous glucose production (EGP) and its suppression during a euglycemic-hyperinsulinemic clamp. Liver fat was measured by magnetic resonance spectroscopy.
RESULTS:
Weight remained stable. Regardless of the order in which the diets were fed, the high-fructose diet was associated with both higher DNL (average 18.6±1.4% vs. 11.0±1.4% for CCHO, P=0.001) and higher liver fat (median +137% of CCHO, P=0.016) in all participants. Fasting EGP and insulin-mediated glucose disposal did not differ significantly, but EGP during hyperinsulinemia was greater (0.60±0.07 vs. 0.46±0.06 mg/kg/min, P=0.013) with the high-fructose diet, suggesting blunted suppression of EGP.
CONCLUSION:
Short-term high-fructose intake was associated with increased DNL and liver fat in healthy men fed weight-maintaining diets.

Schwarz JM1, Noworolski SM, Wen MJ, Dyachenko A, Prior JL, Weinberg ME, Herraiz LA, Tai VW, Bergeron N, Bersot TP, Rao MN, Schambelan M, Mulligan K.
J Clin Endocrinol Metab. 2015 Mar 31:jc20143678. [Epub ahead of print]

Karen L. Teff, Sharon S. Elliott, Matthias Tschöp, Timothy J. Kieffer, Daniel Rader, Mark Heiman, Raymond R. Townsend, Nancy L. Keim, David D’Alessio, and Peter J. Havel
Abstract
Previous studies indicate that leptin secretion is regulated by insulin-mediated glucose metabolism. Because fructose, unlike glucose, does not stimulate insulin secretion, we hypothesized that meals high in fructose would result in lower leptin concentrations than meals containing the same amount of glucose. Blood samples were collected every 30–60 min for 24 h from 12 normal-weight women on 2 randomized days during which the subjects consumed three meals containing 55, 30, and 15% of total kilocalories as carbohydrate, fat, and protein, respectively, with 30% of kilocalories as either a fructose-sweetened [high fructose (HFr)] or glucose-sweetened [high glucose (HGl)] beverage. Meals were isocaloric in the two treatments. Postprandial glycemic excursions were reduced by 66 ± 12%, and insulin responses were 65 ± 5% lower (both P < 0.001) during HFr consumption. The area under the curve for leptin during the first 12 h (−33 ± 7%; P < 0.005), the entire 24 h (−21 ± 8%; P < 0.02), and the diurnal amplitude (peak − nadir) (24 ± 6%; P < 0.0025) were reduced on the HFr day compared with the HGl day. In addition, circulating levels of the orexigenic gastroenteric hormone, ghrelin, were suppressed by approximately 30% 1–2 h after ingestion of each HGl meal (P < 0.01), but postprandial suppression of ghrelin was significantly less pronounced after HFr meals (P < 0.05 vs. HGl). Consumption of HFr meals produced a rapid and prolonged elevation of plasma triglycerides compared with the HGl day (P < 0.005). Because insulin and leptin, and possibly ghrelin, function as key signals to the central nervous system in the long-term regulation of energy balance, decreases of circulating insulin and leptin and increased ghrelin concentrations, as demonstrated in this study, could lead to increased caloric intake and ultimately contribute to weight gain and obesity during chronic consumption of diets high in fructose.
DOI: http://dx.doi.org/10.1210/jc.2003-031855
Published Online: July 02, 2013

Kathleen A. Page, MD; Owen Chan, PhD; Jagriti Arora, MS; Renata Belfort-DeAguiar, MD, PhD; James Dzuira, PhD; Brian Roehmholdt, MD, PhD; Gary W. Cline, PhD; Sarita Naik, MD; Rajita Sinha, PhD; R. Todd Constable, PhD; Robert S. Sherwin, MD
JAMA. 2013;309(1):63-70. doi:10.1001/jama.2012.116975.
Importance: Increases in fructose consumption have paralleled the increasing prevalence of obesity, and high-fructose diets are thought to promote weight gain and insulin resistance. Fructose ingestion produces smaller increases in circulating satiety hormones compared with glucose ingestion, and central administration of fructose provokes feeding in rodents, whereas centrally administered glucose promotes satiety.

Objective: To study neurophysiological factors that might underlie associations between fructose consumption and weight gain.

Design, Setting, and Participants: Twenty healthy adult volunteers underwent 2 magnetic resonance imaging sessions at Yale University in conjunction with fructose or glucose drink ingestion in a blinded, random-order, crossover design.

Main Outcome Measures: Relative changes in hypothalamic regional cerebral blood flow (CBF) after glucose or fructose ingestion. Secondary outcomes included whole-brain analyses to explore regional CBF changes, functional connectivity analysis to investigate correlations between the hypothalamus and other brain region responses, and hormone responses to fructose and glucose ingestion.

Conclusion and Relevance: In a series of exploratory analyses, consumption of fructose compared with glucose resulted in a distinct pattern of regional CBF and a smaller increase in systemic glucose, insulin, and glucagon-like polypeptide 1 levels.