Metabolic and endocrine profiles in response to systemic infusion of fructose and glucose in rhesus macaques

Abstract

Diurnal patterns of circulating leptin concentrations are attenuated after consumption of fructose-sweetened beverages compared with glucose-sweetened beverages, likely a result of limited postprandial glucose and insulin excursions after fructose. Differences in postprandial exposure of adipose tissue to peripheral circulating fructose and glucose or in adipocyte metabolism of the two sugars may also be involved. Thus, we compared plasma leptin concentrations after 6-h iv infusions of saline, glucose, or fructose (15 mg/kg.min) in overnight-fasted adult rhesus monkeys (n = 9). Despite increases of plasma fructose from undetectable levels to about 2 mm during fructose infusion, plasma leptin concentrations did not increase, and the change of insulin was only about 10% of that seen during glucose infusion. During glucose infusion, plasma leptin was significantly increased above baseline concentrations by 240 min and increased steadily until the final 480-min time point (change in leptin = +2.5 +/- 0.9 ng/ml, P < 0.001 vs. saline; percent change in leptin = +55 +/- 16%; P < 0.005 vs. saline). Substantial anaerobic metabolism of fructose was suggested by a large increase of steady-state plasma lactate (change in lactate = 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) infusions (P < 0.001). Therefore, increased adipose exposure to fructose and an active whole-body anaerobic fructose metabolism are not sufficient to increase circulating leptin levels in rhesus monkeys. Thus, additional factors (i.e. limited post-fructose insulin excursions and/or hexose-specific differences in adipocyte metabolism) are likely to underlie disparate effects of fructose and glucose to increase circulating leptin concentrations.

Figure 1

Plasma concentrations of fructose and glucose in conscious adult male rhesus monkeys receiving iv infusions of saline, glucose, or fructose solutions over 360 min. All animals (n = 9) underwent the three treatments on different days in randomized order after a washout period between treatments (see Materials and Methods). Compared with saline treatment, fructose (15 mg/kg·min) elicited a modest increase in glucose levels (90, 240, and 300 min, P < 0.05; 360 min, P < 0.0001), whereas, as expected, during glucose infusion (15 mg/kg·min), there was marked increase of plasma glucose. Fructose was not detectable in plasma from fasted monkeys or during saline or glucose infusion.

Figure 2

Changes of plasma lactate and plasma triglyceride concentrations during 360-min iv infusions of saline, glucose, or fructose in adult male rhesus monkeys. A, Plasma lactate concentrations were significantly increased after glucose and fructose infusions compared with saline infusion (*, P < 0.05; ***, P < 0.001) and were consistently higher after fructose compared with glucose (180 and 300 min, P < 0.05; 360 min, P < 0.01). Baseline lactate concentrations (calculated as the average of values from −10 and 0 min) were 1.98 ± 0.50 mm, 1.48 ± 0.19 mm (glucose), and 1.89 ± 0.33 mm (fructose). B, Plasma triglyceride concentrations decreased significantly during glucose infusion to levels below those observed with saline (*, P < 0.05; **, P < 0.01; ***, P < 0.001). Differences in triglyceride levels comparing fructose to saline were not statistically significant; however, levels during fructose infusion remained significantly higher compared with during glucose infusion at 90 min and beyond (90 and 360 min, P < 0.01; 120–300 min, P < 0.001). Baseline fasting triglyceride concentrations were 54 ± 3 mg/dl (saline), 53 ± 3 mg/dl (glucose), and 50 ± 3 mg/dl (fructose).

Figure 3

Changes of plasma insulin and leptin concentrations during 360-min iv infusions of saline, glucose, or fructose and in the 480-min postinfusion sample in adult male rhesus monkeys. A, Plasma insulin concentrations increased significantly during glucose infusion compared with saline treatment (*, P < 0.05; **, P < 0.01; ***, P < 0.001) and returned to baseline levels after the termination of infusion. Differences in insulin levels during fructose infusion compared with saline infusion were not statistically significant, and levels were significantly below those measured during glucose administration (60 and 180 min, P < 0.05; 90 min, P < 0.001; 120 min, P < 0.01). Baseline fasting insulin concentrations were 37.3 ± 17.1 μU/ml (saline), 25.6 ± 6.5 μU/ml (glucose), and 26.5 ± 5.2 μU/ml (fructose). B, Relative to saline infusion, plasma leptin concentrations were increased progressively during glucose infusion by 240 min infusion and remained elevated at least 2 h after the infusions (*, P < 0.05; ***, P < 0.001 vs. saline). Plasma leptin was not significantly increased during fructose infusion relative to saline treatment, and levels remained lower than those measured during glucose infusion (240 and 300 min, P < 0.05; 360 and 480 min, P < 0.001). Baseline fasting leptin concentrations were 4.4 ± 2.0 ng/ml (saline), 4.9 ± 2.2 ng/ml (glucose), and 4.7 ± 2.4 ng/ml (fructose).