Lipolytic Effect Of Growth Hormone Research Articles

Emerging Mechanisms of GH-Induced Lipolysis and Insulin Resistance.

Growth hormone (GH) is a pleiotropic hormone that coordinates an array of physiological processes including growth and metabolism. GH promotes anabolic action in all tissues except adipose, where it catabolizes stored fat to release energy for the promotion of growth in other tissues. However, chronic stimulation of lipolysis by GH results in an increased flux of free fatty acids (FFAs) into systemic circulation. Hence, a sustained release of high levels of GH contributes significantly to the development of insulin resistance by antagonizing the anti-lipolytic action of insulin. The molecular pathways associated with the lipolytic effect of GH in adipose tissue however, remain elusive. Recent studies have provided molecular insights into GH-induced lipolysis and impairment of insulin signaling. This review discusses the physiological and metabolic actions of GH on adipose tissue as well as GH-mediated deregulation of the FSP27-PPARγ axis which alters adipose tissue homeostasis and contributes to the development of insulin resistance and Type 2 diabetes.

Growth hormone acts along the PPARγ-FSP27 axis to stimulate lipolysis in human adipocytes.

The lipolytic effects of growth hormone (GH) have been known for half a century and play an important physiological role for substrate metabolism during fasting. In addition, sustained GH-induced lipolysis is causally linked to insulin resistance. However, the underlying molecular mechanisms remain elusive. In the present study, we obtained experimental data in human subjects and used human adipose-derived stromal vascular cells (hADSCs) as a model system to elucidate GH-triggered molecular signaling that stimulates adipose tissue lipolysis and insulin resistance in human adipocytes. We discovered that GH downregulates the expression of fat-specific protein (FSP27), a negative regulator of lipolysis, by impairing the transcriptional ability of the master transcriptional regulator, peroxisome proliferator-activated receptor-γ (PPARγ) via MEK/ERK activation. Ultimately, GH treatment promotes phosphorylation of PPARγ at Ser273 and causes its translocation from nucleus to the cytosol. Surprisingly, FSP27 overexpression inhibited PPARγ Ser273 phosphorylation and promoted its nuclear retention. GH antagonist treatment had similar effects. Our study identifies a novel signaling mechanism by which GH transcriptionally induces lipolysis via the MEK/ERK pathway that acts along PPARγ-FSP27 in human adipose tissue.

Physiological and pharmacological basis for the ergogenic effects of growth hormone in elite sports

Growth Hormone (GH) is an important and powerful metabolic hormone that is secreted in a pulsatile pattern from cells in the anterior pituitary, influenced by several normal and pathophysiological conditions. Human GH was first isolated in the 1950s and human derived cadaveric GH was initially used to treat patients with GH deficiency. However, synthetic recombinant GH has been widely available since the mid-1980s and the advent of this recombinant GH boosted the abuse of GH as a doping agent. Doping with GH is a well-known problem among elite athletes and among people training at gyms, but is forbidden for both medical and ethical reasons. It is mainly the anabolic and, to some extent, the lipolytic effects of GH that is valued by its users. Even though GH's rumour as an effective ergogenic drug among athletes, the effectiveness of GH as a single doping agent has been questioned during the last few years. There is a lack of scientific evidence that GH in supraphysiological doses has additional effects on muscle exercise performance other than those obtained from optimised training and diet itself. However, there might be synergistic effects if GH is combined with, for example, anabolic steroids, and GH seems to have positive effect on collagen synthesis. Regardless of whether or not GH doping is effective, there is a need for a reliable test method to detect GH doping. Several issues have made the development of a method for detecting GH doping complicated but a method has been presented and used in the Olympics in Athens and Turin. A problem with the method used, is the short time span (24-36 hours) from the last GH administration during which the test effectively can reveal doping. Therefore, out-of-competition testing will be crucial.However, work with different approaches to develop an alternative, reliable test is ongoing.

Brain specific growth hormone receptor blockade modulates feeding in rats

The anabolic and lipolytic effects of Growth Hormone (GH) have been subject to decades of scientific investigation, therapeutic use and abuse. However, if and how GH influences energy balance specifically via its receptors (GH-R) in the CNS still remains unknown. GH may be both, transported to and expressed by the brain, and GH-Rs are located at hypothalamic circuits known to regulate food intake and energy expenditure. Recently, a specific GH-R antagonist (Pegvisomant (PGV), Pfizer) became available. Being used as an effective therapy for acromegaly, it also provides a unique tool to study action of endogenous and exogenous GH. We investigated the effects of CNS-specific GH-R blockade by PGV on energy homeostasis in rats. 32 Long Evans rats ♂ were cannulated (3. ventricle, positive angiotensin test prior to experiment). Following 72 hours of acclimation to experimental conditions, rats were injected with either PGV, GH (Norditropin, NovoNordisk) or saline (10mg/5µl, n=10–12 each group, 30min. before dark phase, 12/12h light phases). Food intake (FI), water intake (WI), spontaneous physical activity (SPA), energy expenditure (EE) and respiratory quotient (RQ) where measured using a customized 32 cage calorimeter, providing simultaneous, continuous and automated recording and analysis. A single central administration of GH in rats caused a modest increase in food intake as compared to saline treated controls, while central injection of PGV decreased food intake. Effects occurred during the first 24 hours after injection, but was not fully compensated in the 24 hours after that (GH 24h: 22.4±1.6g, GH 48h: 45.7±3.7g, saline 24h: 21.5±2.4g, saline 48h: 43.9±3.7g, PGV 24h: 18.3±2.0g, PGV 48h: 39.5±3.7g). Such single central administration of GH, PGV or saline had no significant effect on EE, RQ, SPA or WI. These results indicate that a specific blockade of endogenous GH action in the brain may decrease food intake in rats.

The lipolytic effects of thyrotropin and isoprenaline are not affected by growth hormone in infant adipocytes.

The lipolytic effects of growth hormone (GH) in children are not fully clarified. In this study, no lipolytic effect of GH on isolated adipocytes obtained at surgery on healthy infants aged 2-5 months and children 3-6 years was observed. Furthermore, GH did not enhance isoprenaline-induced lipolysis, as in adults. The TSH-induced lipolysis which is prominent in neonatal adipocytes was not affected by incubation of adipocytes with GH. Assuming that GH alters adipocyte metabolism primarily by increasing the sensitivity, but not the maximum response, of the beta 2-adrenergic receptor population, it follows that GH, in this sense, should be a less important co-actor in children where beta 2-adrenergic receptors are more abundant.

Growth hormone treatment of hypophysectomized rats increases catecholamine-induced lipolysis and the number of beta-adrenergic receptors in adipocytes: no differences in the effects of growth hormone on different fat depots.

Growth hormone (GH) has a lipolytic effect in adipose tissue but this effect may differ in adipose tissue from various fat depots. This latter possibility was investigated in the present study, in which the effects of GH in vivo on catecholamine-induced lipolysis and the number of beta-adrenergic receptors in isolated adipocytes from different fat depots of hypophysectomized rats were investigated. Female and male Sprague-Dawley rats were hypophysectomized or sham-operated at 45 days of age. One week after the operation, hormonal replacement therapy with L-thyroxine and hydrocortisone acetate was given. In addition, groups of rats were treated with GH (1.33 mg/kg per day, given as two daily subcutaneous injections). After 1 week of hormonal treatment, adipocytes were isolated from the parametrial, epididymal and inguinal fat pads, and glycerol release after catecholamine-stimulation and 125I-cyanopindolol binding were measured. Hypophysectomy resulted in a marked decrease in the lipolytic response to catecholamines. GH treatment significantly increased catecholamine-induced lipolysis with similar effects in adipocytes from parametrial or epididymal and inguinal fat depots in both female and male rats. There were no differences between norepinephrine compared with isoproterenol-induced responses. 125I-cyanopindolol binding was reduced after hypophysectomy and normalized by GH treatment, without differences between parametrial and inguinal adipose tissue regions. We conclude that the lipolytic effects of GH in the rat may partly be mediated by a stimulatory effect on beta-adrenergic receptors in adipocytes. In addition, GH exerted similar effect on catecholamine induced lipolysis and beta-adrenergic receptors in adipocytes from parametrial, epididymal and inguinal fat depots.

Growth hormone increases the lipolytic sensitivity for catecholamines in adipocytes from healthy adults

The lipolytic effect of growth hormone (GH) was investigated in adipocytes obtained during elective surgery from otherwise healthy adults, 18–40 years old. No lipolytic or antilipolytic effect of GH was found when the cells were incubated with GH alone during 30min–6h. When the cells were preincubated with GH during 3h, the lipolytic sensitivity for isoprenaline increased markedly without any change in maximal lipolysis. However, a full effect was only obtained if GH was also present during the incubation with isoprenaline. GH did not alter DB-CAMP, enprophylline, or forskolineinduced lipolysis in human fat cells. In conclusion, GH had no direct lipolytic effect on human fat cells but GH markedly increased the catecholamine sensitivity. The site of the GH effect seems to be in the β-adrenoceptors or in the G s coupling protein.

GROWTH HORMONE INCREASES THE LIPOLYTIC SENSITIVITY FOR CATECHOLAMINES IN HUMAN ADIPOCYTES

The lipolytic effect of growth hormone (GH) was investigated in adipocytes obtained during elective surgery from otherwise healthy adults, 18-40 years old. No lipolytic or antilipolytic effect of GH was found when the cells were incubated with GH alone during 30min-6h. When the cells were preincubated with GH during 3h, the lipolytic sensitivity for isoprenaline increased markedly without any change in maximal lipolysis. However, a full effect was only obtained if GH was also present during the incubation with isoprenaline. The effect of GH was reduced, by cycloheximide. GH did not alter DB-CAMP, enprophylline, or forskoline-induced lipolysis in human fat cells. In conclusion, GH had no direct lipolytic effect on human fat cells but GH markedly increased the catechoiamine sensitivity by a mechanism which involves protein synthesis. The site of the GH effeet seems to be in the β-adreno-ceptors or in the GH coupling protein.

Growth Hormone and Lipids

It has been known for more than 30 years that growth hormone has a lipolytic properties and growth hormone excess (acromegaly) and growth hormone deficiency have been reported to be associated with abnormalities in serum lipoprotein concentrations. Due to the lipolytic effect of growth hormone, its administration in man has been reported to increase plasma nonesterified fatty acid (NEFA) concentrations. Ketone body production increases during acute growth hormone excess as a result of increased NEFA concentrations; similarly, the increase in serum triglycerides may be explained by an increase in substrate (NEFA) supply to the liver for VLDL production. The effect may be enhanced by a simultaneous decrease of serum lipoprotein lipase activity. The cholesterol-lowering effect of growth hormone administration has not been investigated in detail, specifically, the effect of growth hormone on LDL kinetics is unknown. Growth hormone-excess and growth hormone deficiency have been reported to be associated with increased risk for atherosclerosis; an association with serum lipoprotein changes is likely but evidence for a causal link is yet lacking.