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ARS Home » Pacific West Area » Davis, California » Western Human Nutrition Research Center » Obesity and Metabolism Research » Research » Publications at this Location » Publication #221647
Title: Metabolic and Endocrine Profiles in Response to Systemic Infusion of Fructose and Glucose in Rhesus Macaques

Author
item Adams, Sean
item STANHOPE, KIMBER - UCD VET.MED, MOLE. BIO.
item GRANT, RYAN - UCD, NUTR. DEPT., WHNRC
item CUMMINGS, BETHANY - UCD, NUTR.DEPT., WHNRC
item HAVEL, PETER - UCD, NUTR. AND VET.MED.

Submitted to: Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/28/2008
Publication Date: 6/1/2008
Citation: Adams, S.H., Stanhope, K.L., Grant, R.W., Cummings, B.P., Havel, P. 2008. Metabolic and Endocrine Profiles in Response to Systemic Infusion of Fructose and Glucose in Rhesus Macaques. Endocrinology 149(6):3002-3008, 2008.

Interpretive Summary: “Leptin is a key regulator of body weight and other important functions in the body. Diurnal patterns of the plasma levels of this fat tissue-derived hormone were shown in human studies to respond differently to glucose vs. fructose feeding, in that fructose feeding significantly dampened overall levels. This finding raised the possibility that unhealthy metabolic profiles seen with high fructose feeding (i.e., propensity toward weight gain, reduced satiety signals, elevated blood lipids) may in part be due to diminished leptin activities in the body. However, the physiological basis of sugar-dependent leptin responses is not clear. One possibility is that due to the large capacity for fructose uptake by the liver from the gut, little fructose reaches fat tissue to spark leptin production, unlike glucose that spikes postprandially in the circulation. Another possibility is that the limited post-meal insulin surge following fructose limits leptin release since the latter is increased by active fat cell glucose uptake driven by insulin. Finally, differences in how glucose vs. fructose are metabolized in fat cells could underlie smaller leptin excursions with fructose. To better understand these phenomena, fructose or glucose or saline were directly infused into adult monkeys and the pattern of plasma leptin levels assessed. As expected, leptin levels were unaffected by saline control infusions, and were significantly increased with glucose infusion; the latter raised blood glucose and insulin levels significantly. Fructose was a poor leptin secretagogue and did not increase insulin. These results indicate that direct exposure of adipose tissue to fructose failed to elicit a robust leptin release, suggesting that differences in fat cell metabolism of glucose vs. fructose, and/or the lack of insulin response post-fructose, are responsible for sugar-specific differences in postprandial leptin patterns.”

Technical Abstract: Previous studies in human subjects demonstrated that 24 hour diurnal pattern of circulating leptin concentrations is attenuated when fructose-sweetened beverages compared with glucose-sweetened beverages were consumed with meals. The reduction of leptin is likely a result of the reduced postprandial glucose and insulin excursions after fructose consumption. In addition, differences between the sugars with respect to post-meal exposure of adipose tissue to peripheral circulating fructose and glucose levels or in adipocyte metabolism of the sugars may be involved. To address these questions, we compared plasma leptin concentrations over an 8 hour period following 6-hour infusions of saline, or glucose or fructose at a rate of 15 mg/kg/min in overnight-fasted adult rhesus monkeys (n=9), conducted on separate days. Despite increases of plasma fructose from zero to a steady-state level of ~2 mM during fructose infusion (at least four-fold greater than values after fructose ingestion reported in humans), plasma leptin concentrations did not increase and were not different from those observed during saline infusion. In contrast, during glucose infusion, plasma leptin was significantly increased above baseline concentrations by 240 minutes and increased steadily until the 480 minute timepoint (^leptin = +2.5 ± 0.9 ng/ml, p<0.001 vs. saline; %^ = +55 ± 16%; p< 0.005 vs. saline). Unlike during glucose infusion when there was a marked and sustained increase of plasma insulin concentrations, the change in insulin during fructose infusion was only ~10% of that during glucose. Substantial anaerobic metabolism of fructose was suggested by a large increase in steady-state plasma lactate concentrations (increased 1.64 ± 0.15 mM from baseline), which was significantly greater than that during glucose (+0.53 ± 0.14 mM) or saline (-0.51 ± 0.14 mM) infusion (both p<0.001). The results indicate that increased adipose exposure to fructose at a level of 2 mM and an active whole-body anaerobic metabolism of the sugar are not sufficient to increase circulating leptin levels in rhesus monkeys. Thus, additional factors such as the limited insulin excursions in response to fructose and the large degree of hepatic uptake and metabolism of ingested fructose appear to underlie the hexose-specific differences between the effects of fructose and glucose to increase leptin production and circulating leptin concentrations in vivo.