The Pattern of Growth Hormone Delivery to Peripheral Tissues Determines Insulin-Like Growth Factor-1 and Lipolytic Responses in Obese Subjects

Surya, Sowmya; Horowitz, Jeffrey F.; Goldenberg, Naila; Sakharova, Alla; Harber, Matthew P.; Cornford, Andrea S.; Symons, Kathy; Barkan, Ariel L.

doi:10.1210/mend.23.8.9997

Molecular Endocrinology

2009

DOI: 10.1210/mend.23.8.9997

|View full text |Cite

The Pattern of Growth Hormone Delivery to Peripheral Tissues Determines Insulin-Like Growth Factor-1 and Lipolytic Responses in Obese Subjects

Sowmya Surya¹,

Jeffrey F. Horowitz²,

Naila Goldenberg³

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2011

2020

Publication Types

Select...

Article5

Relationship

Self Cite1

Independent4

Authors

Journals

Cited by 5 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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 direct inhibition of insulin signaling (1), as well as indirectly by increasing lipolysis (18), which in turn can alter insulin action via increasing fatty acid infiltration into insulin-responsive tissues.…”

mentioning

confidence: 83%

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

Cornford¹,

Barkan

Hinko³

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

View full text Add to dashboard Cite

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...

show abstract

mentioning

confidence: 83%

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

Cornford¹,

Barkan

Hinko³

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

View full text Add to dashboard Cite

show abstract

“…day, with the most pronounced release occurring nocturnally (19,47). This pulsatile release has multiple effects on peripheral tissue, with one of its key functions being regulation of body fat and lean tissue (30,47).…”

mentioning

confidence: 99%

“…This pulsatile release has multiple effects on peripheral tissue, with one of its key functions being regulation of body fat and lean tissue (30,47). Recent work in humans has demonstrated that continuous GH administration primarily augments hepatic and muscle IGF-I, while only pulsatile GH administration augments adipose tissue lipolysis (47). One of the most potent stimulators of pulsatile GH release is exercise (48).…”

mentioning

confidence: 99%

“…In obese individuals, reductions in spontaneous GH secretion (as much as 6% for each unit increase in BMI) and the half-life of circulating GH have been reported (decreases from 15 to 11 min) (46). Additionally, the biological effects of GH in obese humans may not be determined merely by the overall magnitude of GH output but, rather, by complex pulsatile patterns of GH presentation to peripheral tissues (47).…”

mentioning

confidence: 99%

“…The dosages of GH administration have varied, but it seems that low dosages are effective in reducing fat mass and abdominal fat mass (47). GH administration has been successful in reducing abdominal/visceral fat deposits (28) and can prove to be beneficial at reducing obesity-related comorbidities that may be caused by the increased abdominal/visceral adipose tissue (6).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Immunoreactive and bioactive growth hormone responses to resistance exercise in men who are lean or obese

Thomas

Kraemer

Kennett

et al. 2011

Journal of Applied Physiology

View full text Add to dashboard Cite

The present study was designed to examine the effects of a highvolume, whole body acute resistance exercise (RE) protocol on immunoreactive GH (iGH), bioactive GH (bGH), and GH-binding protein (GHBP) in sedentary lean and obese men. Nine obese (mean Ϯ SD: 20.8 Ϯ 2.1 yr old, 177.0 Ϯ 4.1 cm height, 108.7 Ϯ 15.9 kg body mass, 37.6 Ϯ 5.29% body fat) and nine lean (20.1 Ϯ 2.1 yr old, 177.8 Ϯ 8.7 cm height, 71.7 Ϯ 5.8 kg body mass, 14.7 Ϯ 3.54% body fat) men completed an acute RE protocol (6 exercises, 3 sets of 10 repetitions at 85-95% of 10 repetitions maximum with 120-and 90-s rest periods), and blood samples were collected before, at the midpoint, and immediately after exercise and during recovery (ϩ50, ϩ70, and ϩ110). In contrast to prior studies, which examined acute responses to cardiovascular exercise protocols, groups did not differ in iGH response to the exercise stimulus. However, bGH concentrations overall were significantly lower in the obese than the lean participants (P Ͻ 0.001). Additionally, obese individuals had significantly higher GHBP concentrations (P Ͻ 0.001). Results suggest that obese and lean sedentary men performing a high-volume, whole body acute RE protocol demonstrate similar increases in iGH. Blunted bGH and elevated GHBP concentrations are indicative of altered GH activity associated with obesity. Prior research findings of blunted iGH response may be attributable to RE protocols not equated on relative intensity or volume. These results underscore the complexity of pituitary biology and its related mechanisms and may have implications for exercise prescription in the treatment of obesity.

show abstract

Stimulation of endogenous pulsatile growth hormone secretion by activation of growth hormone secretagogue receptor reduces the fat accumulation and improves the insulin sensitivity in obese mice

Huang

et al. 2020

FASEB j.

View full text Add to dashboard Cite

Obese individuals often show low growth hormone (GH) secretion, which leads to reduced lipid mobilization and further fat accumulation. Pharmacological approaches to increase GH levels in obese individuals by GH injection or GH‐releasing hormone receptor agonist showed promising effects on fat reduction. However, side effects on glucose metabolism and the heavy costs on making large peptides hindered their clinical application. Here, we tested whether stimulation of endogenous GH secretion by a synthetic GH secretagogue receptor (GHSR) agonist, hexarelin, improved the metabolism in a hyperphagic obese mouse model. Male melanocortin 4 receptor knockout mice (MC4RKO) were pair‐fed and received continuous hexarelin (10.56 μg/day) or vehicle infusion by an osmotic pump for 3‐4 weeks. Hexarelin treatment significantly increased the pulsatile GH secretion without detectable alteration on basal GH secretion in MC4RKO mice. The treated mice showed increased lipolysis and lipid oxidation in the adipose tissue, and reduced de novo lipogenesis in the liver, leading to reduced visceral fat mass, reduced triglyceride content in liver, and unchanged circulating free fatty acid levels. Importantly, hexarelin treatment improved the whole‐body insulin sensitivity but did not alter glucose tolerance, insulin levels, or insulin‐like growth factor 1 (IGF‐1) levels. The metabolic effects of hexarelin were likely through the direct action of GH, as indicated by the increased expression level of genes involved in GH signaling pathways in visceral adipose tissues and liver. In conclusion, hexarelin treatment stimulated the pulsatile GH secretion and reduced the fat accumulation in visceral depots and liver in obese MC4RKO mice with improved insulin sensitivity without altered levels of insulin or IGF‐1. It provides evidence for managing obesity by enhancing pulsatile GH secretion through activation of GHSR in the pituitary gland.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

The Pattern of Growth Hormone Delivery to Peripheral Tissues Determines Insulin-Like Growth Factor-1 and Lipolytic Responses in Obese Subjects

Cited by 5 publications

References 0 publications

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

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

Immunoreactive and bioactive growth hormone responses to resistance exercise in men who are lean or obese

Stimulation of endogenous pulsatile growth hormone secretion by activation of growth hormone secretagogue receptor reduces the fat accumulation and improves the insulin sensitivity in obese mice

Contact Info

Product

Resources

About