High-intensity exercise and carbohydrate supplementation do not alter plasma visfatin.

Author:Mellick, Paul F.
Position::Research article - Report


Visfatin is a protein preferentially expressed in visceral fat that has been implicated in multiple cellular functions (Rongvaux et al. 2002; Samal et al. 1994; Xie et al. 2007). These cellular functions include inflammation, regulation of nicotinamide adenine dinucleotide (NAD) biosynthesis, and glucose metabolism. Recently, the role of visfatin in glucose metabolism has generated considerable interest since the underlying mechanism related to the influence of visfatin on glucose uptake has yet to be identified. One popular proposed mechanism, displayed in hyperglycemic mice and human osteoblasts, is the visfatin-mediated increase in glucose uptake via increasing tyrosine phosphorylation of the insulin receptor, insulin receptor substrates 1 and 2 (IRS-1, IRS-2), and phosphatidylinositol 3-kinase (PI3K) (Xie et al. 2007). This mechanism may contribute to the restoration of insulin pathway sensitivity observed in hyperglycemic states (Choi et al. 2007; Fukuhara et al. 2005; Haider et al. 2006). Moreover, visfatin-mediated glucose uptake was observed to be dose-dependent in human mesangial cells. This effect of visfatin may be a result of visfatin's ability to noncompetitively bind to the insulin receptor (Song et al. 2008). While this evidence suggests that visfatin influences glucose uptake on an intracellular level (possibly through its role in the NAD biosynthetic pathway), few studies have examined the extracellular relationship between plasma visfatin and glucose uptake.

The interaction between plasma visfatin and extracellular glucose regulation during exercise is not fully understood. Following chronic aerobic exercise training, resting blood glucose decreases, which is paralleled by plasma visfatin levels (Brema et al. 2008; Choi et al. 2007; Haider et al. 2006; Haus et al. 2009; Jorge et al. 2011). Correspondingly, resting plasma visfatin levels are above acceptable levels in hyperglycemic individuals (Chang et al. 2011). These data suggest that in aerobic training studies completed in humans, plasma visfatin may be altering glucose regulation in a manner similar to insulin, since the plasma levels of both hormones respond to glucose similarly (Fukuhara et al. 2005; Revollo et al. 2007). The effect of visfatin on glucose regulation in acute stress is also unclear, due to conflicting published results (Frydelund et al. 2007; Ghanbari-Niaki et al. 2010; Jurimae et al. 2009). In elite rowers, 2 hr of rowing performed at 80% of heart rate reserve resulted in significant decreases in plasma visfatin and insulin, despite no significant change in blood glucose (Jurimae et al. 2009). Conversely, visfatin was elevated more than two-fold after one exercise session including 7 bouts of 35 m sprint runs, and this elevation was mirrored by blood lactate, plasma insulin and blood glucose (Ghanbari-Niaki et al. 2010). Finally, in healthy subjects that cycled for 3 hr at 60% of V[O.sub.2] max, there was no significant change in plasma visfatin, despite a significant decrease in plasma insulin and blood glucose (Frydelund-Larsen et al. 2007).These seemingly contradictory results are likely due to the varying exercise protocols, as well as the varying subject characteristics.

Although the exercise literature is murky, carbohydrate intake studies can be used to provide some clarity in the response pattern of plasma visfatin compared to changing plasma glucose concentrations. Data from two carbohydrate intake studies in individuals with impaired insulin function suggest that plasma visfatin augments glucose uptake in a manner independent of insulin (Park et al. 2013; Rezvan et al. 2012). Research regarding carbohydrate intake and visfatin is limited, but available data suggest that glucose intake may suppress visfatin release; however, the exact mechanism is still unclear (Bala et al. 2011). To our knowledge, no study has controlled for both carbohydrate supplementation and exercise in order to assess the relationship between visfatin, insulin, and blood glucose. In order to gain a better understanding of how plasma visfatin may affect glucose uptake, it is necessary to examine it in individuals without impaired insulin function. Therefore, the purpose of this study was to further investigate the effect of acute exercise and carbohydrate supplementation on plasma visfatin in an effort to further understand any role that visfatin may have in blood glucose regulation.


The University of North Carolina at Greensboro Institutional Review Board approved all methods. Written informed consent was received from all subjects, and a screening session was completed prior to the exercise sessions. During the screening session, abdominal circumference and BMI were assessed, and a Wingate test was performed to determine mean power (MP). Resistance during the Wingate test was 7.5% of body weight. Mean power was calculated as MP (W) = load (Kg on flywheel) x average revolutions x 11.765. Wingate tests have been used in previous studies to determine workload for a high-intensity interval exercise (Burgomaster et al. 2008; Franchini et al. 2016; Gibala et al. 2014) Resting heart rate (HR), blood pressure, medical history, and exercise history were also assessed. During the screening session, body composition and body fat distribution were determined by dual energy x-ray absorptiometry (DXA; Prodigy Advanced, GE Lunar). Truncal fat was determined by DXA analysis and defined as any fat located below the neck and not on either limb. Truncal fat was assessed since it has been shown to be a direct indicator of the amount of visceral fat (Dwimartutie et al. 2010; Parikh et al. 2007). A 3-day dietary record was given to all subjects, and was completed for the 3 days prior to each exercise session. Dietary records were analyzed for total caloric intake and macronutrient percentage using the My Fitness Pal software (MyFitnessPal, LLC, San Francisco, CA).

After initially screening 12 individuals, 10 sprint-trained males between the ages of 18 and 30 with less than 20% body fat qualified for the study. A group of 10 subjects was determined via power analysis to be appropriate to yield a power of 0.80 with an alpha value of 0.05. Sprint-trained was defined as participating in some form of high-intensity interval exercise at least 2 times per week for at least the last 4 weeks, using leg muscles that would be utilized for cycling. The majority of subjects (n = 6) cycled regularly, four of whom cycled at least 100 miles per week. Furthermore, mean peak power for all subjects was 1068.6 [+ or -] 79.3 watts (W), which ranks above the 95th percentile (Maud and Shultz 1989).

Subjects reported to the lab two times after overnight fasts. An indwelling intravenous (IV) catheter was placed in the arm of the subject so that blood draws could be taken throughout the session. The first blood draw was taken 30 min prior to exercise. Immediately after the first blood draw, a supplement of either 50 g of carbohydrates (236 ml of Gatorade G01 Prime Solution; 0g of protein, 0g of fat) or 236 ml of sugar-free Kool-Aid was administered as the carbohydrate supplementation (CHO) or the placebo control (CON), respectively. The order of supplement for each subject was determined by a coin flip to maintain randomness. Exercise began with a 6-min warm-up at a standardized intensity of 50 W. After the warm-up, each subject completed four 3-min exercise bouts at 50% of MP, separated by 6 min of active recovery at an intensity of 50 W. This timing and intensity was chosen based on a pilot study, as it elicited the necessary alterations in blood glucose (unpublished). Subjects were given water ad libitum, and water intake was not recorded. Blood draws were taken immediately prior to and immediately after each high-intensity interval. The final draws were taken 15 min and 30 min post exercise. These time points were chosen since exercise-induced changes in visfatin were shown to be reduced to baseline levels 30 min post exercise (Jurimae et al. 2009). Finally, in order for some subjects to be able to complete each bout, resistance was...

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