Suppression in growth hormone during overeating ameliorates the increase in insulin resistance and cardiovascular disease risk

Abstract

Cornford AS, Barkan AL, Hinko A, Horowitz JF. Suppression in growth hormone during overeating ameliorates the increase in insulin resistance and cardiovascular disease risk. Am J Physiol Endocrinol Metab 303: E1264 -E1272, 2012. First published September 25, 2012; doi:10.1152/ajpendo.00320.2012.-Previously, we reported that overeating for only a few days markedly suppressed the secretion of growth hormone (GH). The purpose of the present study was to determine the role of this reduction in GH concentration on key metabolic adaptations that occur during 2 wk of overeating. Nine nonobese, healthy adults were admitted to the hospital for 2 wk, during which time they ate ϳ4,000 kcal/day (70 kcal·kg fat-free mass Ϫ1 ·day Ϫ1 ; 50% carbohydrate, 35% fat, and 15% protein), and their plasma GH concentration was allowed to decline naturally (control). An additional eight subjects underwent the same overeating intervention and received exogenous GH treatment (GHT) administered in four daily injections to mimic physiological GH secretion throughout the 2-wk overeating period. We measured plasma insulin and glucose concentrations in the fasting and postprandial state as well as fasting lipolytic rate, proteolytic rate, and fractional synthetic rate (FSR) using stable-isotope tracer methods. GHT prevented the fall in plasma GH concentration, maintaining plasma GH concentration at baseline levels (1.2 Ϯ 0.2 ng/ml), which increased fasting and postprandial assessments of insulin resistance (P Ͻ 0.05) and increased fasting lipidemia (all P Ͻ 0.05 vs. control). In addition, preventing the suppression in GH with overeating also blunted the increase in systemic proteolysis (P Ͻ 0.05 GHT vs. control). However, GHT did not alter lipolysis or FSR in response to overeating. In conclusion, our main findings suggest that the suppression in GH secretion that naturally occurs during the early stages of overeating may help attenuate the insulin resistance and hyperlipidemia that typically accompany overeating. obesity; lipolysis; proteolysis; muscle protein fractional synthetic rate; overfeeding WEIGHT GAIN CAN ONLY OCCUR when energy intake exceeds energy expenditure (i.e., positive energy balance), and even a relatively modest positive energy balance can result in an individual becoming overweight and obese over time. Although the metabolic complications of obesity have been well described (16,18,31), far less is known about the dynamic metabolic adaptations that occur in response to overeating. Importantly, we reported previously that even just a few days of overeating profoundly suppressed plasma growth hormone (GH) concentration in nonobese adults (7). However, the metabolic consequences of this acute suppression in plasma GH concentration with overeating are not known.GH has been identified as an important regulator of several metabolic processes. For example, we (39) and others (4,9) found that the normal pulsatile pattern of GH secretion augments lipolytic rate. Additionally, GH has been reported to impair insulin sensitivity through...

Increased adiposity and insulin correlates with the progressive suppression of pulsatile GH secretion during weight gain

“…We conclude that impaired pulsatile GH secretion in the mouse occurs alongside progressive weight gain and thus precedes the development of obesity. Moreover, our findings are in agreement with the recent clinical findings by Cornford et al (2012), demonstrating a potential role for the GH/insulin axis to sustain NEFA and glucose homeostasis. Thus, we anticipate that impaired pulsatile GH secretion relative to increased dietary intake contributes to increased adiposity and the eventual development of obesity.…”

“…Given that GH secretion is recovered after significant weight loss, it is thought that impaired GH secretion is a consequence of obesity (Rasmussen et al 1995, Nam & Marcus 2000. Recent data, however, demonstrate the rapid suppression of GH secretion relative to excess calorie consumption (Cornford et al 2011(Cornford et al , 2012. In this context, impairments to GH secretion may precede obesity, while contributing to normal endocrine adaptations that minimize the physiological impact of sustained positive energy balance.…”

“…Overeating (Brons et al 2009) and elevated GH (Barbour et al 2005) impairs insulin signaling. Accordingly, it was found that the suppression of GH secretion following excess food consumption in humans ameliorates insulin resistance and sustains optimal meal tolerance (Cornford et al 2012). Thus, the suppression of GH secretion during periods of excess food consumption appears to be a pivotal physiological adaptation to promote insulin-driven lipogenesis, thereby preventing hyperlipidemia (Cornford et al 2012).…”

“…Accordingly, it was found that the suppression of GH secretion following excess food consumption in humans ameliorates insulin resistance and sustains optimal meal tolerance (Cornford et al 2012). Thus, the suppression of GH secretion during periods of excess food consumption appears to be a pivotal physiological adaptation to promote insulin-driven lipogenesis, thereby preventing hyperlipidemia (Cornford et al 2012). Based on our observations, we propose an extension of the findings by Cornford et al (2012) and anticipate that the maintenance of GH/insulin balance throughout extended periods of excess calorie consumption provides a key physiological mechanism to cope with prolonged positive energy balance.…”

“…Correlative studies assessing the relationship between adiposity and the secretion of GH provide essential information to identify potential factors that suppress GH secretion in obesity (Gill et al 1997, Vahl et al 1997, Veldhuis et al 2009). Recent measures demonstrate that impairments in pulsatile GH secretion in humans precede dietary-induced weight gain (Cornford et al 2011(Cornford et al , 2012 and that the suppression of GH secretion with increased food consumption improves meal tolerance (Cornford et al 2012). Accordingly, the progressive decline in GH secretion may exacerbate dietary-induced weight gain and ultimately contribute to the development of obesity.…”