Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.34 (lipoprotein lipase)
 7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lipid metabolic disorders in chronic renal insufficiency (CRI) are related to increased hepatic lipid synthesis, reduced triglyceride removal coupled with insulin insensitivity and impaired lipoprotein lipase activity. Growth hormone is lipolytic, and the effects of recombinant human growth hormone (rhGH) on the hypercholesterolemia of CRI are unsettled. To test this question, we gave rhGH for 14 days at a dosage of 3 units/day intraperitoneally to two-stage, 5/6 nephrectomized, male Sprague-Dawley rats (n = 18) compared to sex- and age-matched control (n = 27) and CRI (n = 40) rats. At the end of the study, CRI rats and those treated with rhGH had a similar degree of renal impairment, as assessed by serum concentrations (mean +/- SEM) of urea nitrogen (49 +/- 3 vs. 54 +/- 4 mg/dl), creatinine (0.9 +/- 0.0 vs. 1.0 +/- 0.1 mg/dl) and cumulative food intake (311 +/- 8 vs. 290 +/- 12 g). Serum urea nitrogen (16 +/- 4 mg/dl) and creatinine (0.4 +/- 0.1 mg/dl) concentrations as well as food intake (412 +/- 9 g) of control rats were significantly (p < 0.0001) different. Serum cholesterol concentration of CRI rats treated with rhGH (87 +/- 3 mg/dl) was not higher than those of CRI rats (81 +/- 2 mg/dl, p < 0.1338) but was significantly higher than in control rats (55 +/- 3 mg/dl, p < 0.0001). CRI rats treated with rhGH showed a similar serum albumin concentration and lower serum glucose than CRI rats (0.9 +/- 0.1 vs. 0.9 +/- 0.0 g/dl and 144 +/- 4 vs. 163 +/- 3 mg/dl, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypercholesterolemia in rats with chronic renal insufficiency not aggravated by recombinant human growth hormone. 147 89

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.
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PMID:Growth hormone and lipids. 180 82

Growth hormone regulates in a positive way the expression of the lipoprotein lipase gene at a transcriptional level in preadipocyte Ob1771 cells. Inhibition by serum components of this expression was investigated upon stimulation by growth hormone. Low-molecular weight, lipid-soluble components (a serum lipid extract, corticosteroids and oleic acid) and high-molecular weight, hydrophilic components (TGF-beta and those present in delipidated serum) were inhibitory. Inhibition of the expression of LPL mRNAs and that of LPL activity were parallel. It is concluded that the regulation of the expression of LPL gene occurs likely at a transcriptional level and that a balance between multiple effectors present in serum are active in an opposite manner.
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PMID:Inhibition by serum components of the expression of lipoprotein lipase gene upon stimulation by growth hormone. 230 31

A direct and modulating effect of growth hormone (GH) on the regulation of the lipoprotein lipase (LPL) gene has been shown in preadipocyte Ob1771 cells. Growth hormone acts as a modulator within the physiological range of concentrations and regulates the abundance of the two species of LPL mRNAs (3.3 and 3.7 kb) in a differentiation-dependent manner, the stimulation factor being between 4- and 7-fold. The regulation of LPL gene expression by GH is rapid (2 to 8 h) and similar for both mRNA species. It is reversible and takes place primarily at a transcriptional level. Parallel increases of LPL mRNAs, LPL protein, and LPL activity are observed. The expression of both cellular and secreted activities is stimulated by GH. The role of GH is mediated, at least in part, by means of activation of protein kinase C. In the presence of 4-beta-phorbol-12-myristate 13-acetate (PMA), a parallel increase of LPL mRNA content and LPL activity is observed at half the values obtained upon stimulation by GH. The kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) abolishes completely the PMA-induced accumulation but decreases only by half that induced by GH. Like H7, staurosporine, polymixin B, and sphingosine inhibit only by half the stimulatory effect of GH on the expression of the LPL gene. These results show for the first time a rapid regulation of the LPL gene expression at a transcriptional level. Ob1771 cells should be helpful in gaining some insights in the promoter function of the LPL gene and the trans-acting factors involved in its regulation.
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PMID:Transcriptional control of the expression of lipoprotein lipase gene by growth hormone in preadipocyte Ob1771 cells. 240 59

Growth hormone (GH) is required for the terminal differentiation of preadipose Ob1771 cells that have entered the differentiation program as evidenced by the expression of early marker genes (pOb24 and lipoprotein lipase). Induction of c-fos mRNA within 15 min and induction of insulin-like growth factor I mRNA within a few hours take place in response to GH. The role of GH is mediated, at least in part, by means of the activation of protein kinase C, as shown by the inhibition of epidermal growth factor binding and by the expression of the c-fos gene, and is thus analogous to the action of prostaglandin F2 alpha and 4 beta-phorbol-12,13-didecanoate in this respect. However, in contrast to that of the c-fos gene, the regulation of insulin-like growth factor I gene expression by GH is not mediated by means of the activation of protein kinase C, and, in line with this, prostaglandin F2 alpha and 4 beta-phorbol-12,13-didecanoate were ineffective. GH and prostaglandin F2 alpha were able to stimulate the formation of diacyglycerol within a few seconds, but GH did not elicit an accumulation of inositol phosphates, in contrast to that generated by prostaglandin F2 alpha. We conclude that the transduction signal of GH action in c-fos mRNA induction is the formation of diacylglycerol and that the mechanism whereby GH can activate protein kinase C is associated with a phospholipase C-mediated hydrolysis of glycerophospholipids other than inositol phospholipids.
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PMID:Growth hormone stimulates c-fos gene expression by means of protein kinase C without increasing inositol lipid turnover. 249 51

Hormones exert powerful influences on body fat distribution in humans. Studies under fully controlled conditions in vitro have indicated that cortisol and insulin facilitate lipid accumulation by expressing lipoprotein lipase (LPL). Growth hormone (GH) abolishes this and turns metabolism towards lipid mobilization. Testosterone and GH inhibit LPL and stimulate lipolysis markedly. Cortisol effects are mediated via a glucocorticoid receptor, and testosterone effects via an androgen receptor, the density of which appears to be higher in visceral than subcutaneous adipose tissue. The receptor-mediated effects are probably expressed via transcription of appropriate genes. The female sex steroids also regulate adipose tissue metabolism, but apparently not directly in the absence of specific cellular receptors. Oestrogens seem to exert net effects similar to those of testosterone. These results of cellular studies agree well with in-vivo studies of triglyceride uptake and turnover in different adipose tissue regions. Furthermore, clinical entities with characteristic disturbances in hormone levels show the expected redistribution patterns.
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PMID:Hormonal control of regional fat distribution. 940 18

Growth hormone (GH) has diverse and still not fully elucidated effects on adipose tissue. Both preadipocytes and mature adipocytes possess specific GH receptors. GH may mediate its actions via these receptors, but some effects are indirectly mediated through the GH-mediated secretion of insulin-like growth factor-I (IGF-I). IGF-I may then act back on the adipose tissue in an autocrine/paracrine manner. In primary cultures of adipose precursor cells obtained from human or rat adipose tissue, GH is found to stimulate the proliferation of these immature cells and reduce their differentiation to mature adipocytes. During long-term incubation and in in vivo studies, GH has a pronounced lipolytic effect. Whether this lipolytic effect is a direct effect of GH or more indirectly mediated, for instance, via inhibition of the action of antilipolytic compounds (e.g. adenosine, prostaglandins and insulin) is presently unknown. Finally, GH produces a pronounced inhibition of adipose tissue lipoprotein lipase activity. This enzyme plays a main role for hydrolysing triglycerides in the blood circulation in the adipose tissue and then for triglyceride accumulation in adipose cells. Thus, GH inhibits adipocyte differentiation, reduces triglyceride accumulation and increases lipolyses--all mechanisms which reduce adipose tissue mass.
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PMID:Action of growth hormone in adipose tissue. 943 54

The regulation of adipose tissue mass and energy expenditure is currently subject to intensive research, which primarily relates to the discovery of leptin. Leptin is a peptide, which is the product of the obese (ob) gene expressed in adipose tissue of several species icluding humans. Leptin is supposed to serve both as an index of fat mass and as a sensor of energy balance. Administration of recombinant murine leptin in ob/ob-mice, which do not produce leptin, decreases food intake and increases thermogenesis both of which result in a reduction in body weight and adipose tissue mass. The calorigenic effect of leptin presumably acts through an increase in sympathetic outflow which in turn activates the beta3 adrenergic receptor in brown adipose tissue. The regulation and action of endogenous leptin in humans are less well understood, and clinical grade recombinant human leptin is so far not available. Serum leptin correlates logarithmically with total body fat in both normal weight and obese subjects, which suggest insensitivity to leptin in obese patients. Furthermore, more rapid excursions in serum leptin have been reported following short-term changes in caloric intake and administration of insulin. Growth hormone (GH) exerts pronounced effects on lipid metabolism and resting energy expenditure. The lipolytic actions of GH appear to involve both increased sensitivity to the beta-adrenergic pathway, and a suppression of adipose tissue lipoprotein lipase activity. The calorigenic effects of GH have been shown not only to be secondary to changes in lean body mass. Growth hormone administration furthermore increases the peripheral conversion of thyroxine to triiodothyronine, which may contribute to the overall actions of GH on fuel and energy metabolism. So far, little is known about the effects of GH and iodothyronines on serum leptin levels in humans. We therefore measured serum leptin levels and energy expenditure before and after the administration of GH and triiodothyronine, alone and in combinaion, in a randomized double-blind placebo-controlled study in healthy young male adults. The dose of triiodothyronine was selected to obtain serum levels comparable to those seen after GH administration.
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PMID:Serum leptin concentrations during short-term administration of growth hormone and triiodothyronine in healthy adults: a randomised, double-blind placebo-controlled study. 1007 48

Growth hormone (GH) is not only the major regulator of postnatal somatic growth but also exerts profound effects on body composition through a combination of anabolic, lipolytic and antinatriuretic actions. GH enhancement of the lipolytic activity of adipose tissue in combination with a reduction of triglyceride accumulation via inhibition of lipoprotein lipase activity appears to be the major mechanism by which GH results in a reduction of the total fat mass. Recently, much progress has been made in understanding the molecular mechanism by which GH affects cellular function. This review provides a brief discourse and summary of the mechanism of effects of GH on preadipocyte/adipocyte function. It is intended to provide a functional understanding of the mechanism of action of GH as it relates to adipogenesis and adipocyte function.
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PMID:The mechanism of effect of growth hormone on preadipocyte and adipocyte function. 1211 89

Lipid storage and breakdown is mainly controlled by lipoprotein lipase and hormone-sensitive lipase. The aim of this work was to elucidate whether growth hormone mediated loss of adipose tissue involves a concerted action on tissue lipases, and to what degree such events are modulated by dietary regimen. Twelve-month-old rats fed first a high-fat diet or a low-fat diet for 14 weeks were injected with saline or growth hormone (4 mg/kg/d) for four days or three weeks in different combinations with either high- or low-fat diets. In adipose tissue, growth hormone generally inhibited lipoprotein lipase and also attenuated the inhibiting effect of insulin on hormone-sensitive lipase activity. Growth hormone treatment combined with restricted high-fat feeding reduced the activity of both lipases in adipose tissue and stimulated hormone-sensitive lipase in muscle. Generally, plasma levels of free fatty acids, glycerol and cholesterol were reduced by growth hormone, and in combination with restricted high-fat feeding, triglyceride levels improved too. We conclude that growth hormone inhibits lipid storage in adipose tissue by reducing both lipoprotein lipase activity and insulin's inhibitory action on hormone-sensitive lipase. We also propose that growth hormone's effects on tissue lipases and blood lipids are modulated by dietary regimen.
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PMID:Growth hormone-mediated breakdown of body fat: effects of GH on lipases in adipose tissue and skeletal muscle of old rats fed different diets. 1277 68


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