Effect of acute pharmacological reduction of plasma free fatty acids on growth hormone (GH) releasing hormone-induced GH secretion in obese adults with and without hypopituitarism

In obesity, there is a markedly decreased GH secretion. The diagnosis of GH deficiency (GHD) in adults is based on peak GH responses to stimulation tests. In the severely obese, peak GH levels after pharmacological stimulation are often in the range that is observed in hypopituitary patients. To distinguish obese subjects from GHD patients, it will be necessary to demonstrate that reduced GH responsiveness to a given test is reversible in the former, but not in the latter, group. Recent studies have shown that reduction of plasma free fatty acids (FFA) with acipimox in obese patients restores their somatotrope responsiveness. There are no data evaluating GH responsiveness to acipimox plus GHRH in obese adults with hypopituitarism. The aim of the present study was to evaluate the effect of acute pharmacological reduction of plasma FFA on GHRH-mediated GH secretion in obese normal subjects and obese adults with hypopituitarism. Eight obese patients with a body mass index of 34.2+/-1.2; eight obese adults with hypopituitarism, with a body mass index of 35.5+/-1.9; and six control subjects were studied. All the patients showed an impaired response to an insulin-tolerance test (0.15 U/kg, i.v.), with a peak GH secretion of less than 3 microg/L. Two tests were carried out. On one day, they were given GHRH (100 microg, i.v., 0 min), preceded by placebo; and blood samples were taken every 15 min for 60 min. On the second day, they were given GHRH (100 microg, i.v., 0 min), preceded by acipimox (250 mg, orally, at -270 min and -60 min); and blood samples were taken every 15 min for 60 min. The administration of acipimox induced a FFA reduction during the entire test. Normal control subjects had a mean peak (microg/L) of 23.8+/-4.8 after GHRH-induced GH secretion; previous acipimox administration increased GHRH-induced GH secretion, with a mean peak of 54.7+/-14.5. In obese patients, GHRH-induced GH secretion was markedly reduced, with a mean peak (microg/L) of 3.9+/-1; previous administration of acipimox markedly increased GHRH-mediated GH secretion, with a mean peak of 16.0+/-3.2 (P < 0.05). In obese adults with hypopituitarism, GHRH-induced GH secretion was markedly reduced, with a mean peak (microg/L) of 2+/-0.7; previous acipimox administration did not significantly modify GHRH-mediated GH secretion, with a mean peak of 3.3+/-1.1 (P < 0.05). The GH response of obese patients and obese adults with hypopituitarism was similar after GHRH alone. In contrast, the GH response after GHRH plus acipimox, was markedly decreased in obese adults with hypopituitarism (mean peak, 3.3+/-1.1), compared with obese patients (mean peak, 16.0+/-3.2) (P < 0.05) and control subjects (mean peak, 54.7+/-14.5) (P < 0.01). In conclusion, GH secretion, after GHRH-plus-acipimox administration, is reduced in obese adults with hypopituitarism patients, when compared with obese normal patients. Testing with GHRH plus acipimox is safe and is free from side effects and could be used for the diagnosis of GHD in adults.     

Combined nitroglycerin-heparin infusion in mesenteric venous thrombosis

Surgical treatment of venous mesenterial thrombosis (VMT) may result in a short bowel-syndrome. We report the successful outcome of combined intravenous heparin and nitroglycerine in a case of VMT followed by a limited resection of small bowel.     

Normal abomasal electromyography and emptying in sheep and the effects of intraabomasal volatile fatty acid infusion

Electromyographic activity and emptying of the abomasum were studied in 3 sheep. Pacesetter potentials (PP), with a frequency of 6.06 +/- 0.05 (X +/- SEM) cycles/minute and propagated distally with an increased conduction velocity approaching the pylorus, were recorded from the distal 11 cm of the antrum. Spike burst and fused action potentials (AP) were superimposed on a variable percentage of PP. The aborad propagation of both types of AP was associated with abomasal emptying at the net rate of 12.61 +/- 1.38 (X +/- SEM) ml/minute. Intraabomasal infusion of 50 ml of a 300 mM solution of either acetic, propionic, or butyric acid was associated with a marked decrease in abomasal AP activity and in the emptying rate. Butyric acid was most effective, followed by propionic and acetic acids. The importance of the results in relation to the pathogenesis of left displaced abomasum (LDA) in dairy cows was noted.     

Effect of fatty acids on lipid and apoprotein secretion and association in hepatocyte cultures

Increasing availability of free fatty acids (FFA) to liver results in enhanced rates of secretion of triglycerides in lipoproteins. However, as FFA uptake increases, triglyceride secretory rates reach a plateau and esterified fatty acids accumulate intracellularly, suggesting that something is limiting lipid transport out of the liver. One possibility could be the limited availability of apoproteins. To test this hypothesis, primary rat hepatocytes in culture were incubated with increasing amounts of FFA (0-2.1 mumol/dish) and the amounts of lipids and apoproteins inside the cells and in culture media were measured; the latter by specific radioimmunoassays. Media also were fractionated on Sepharose 2B and 6B columns and the elution profiles of apoproteins were obtained. With exposure to increasing amounts of free fatty acids, hepatocytes took up more fatty acids and intracellular levels of triglycerides rose (from 71 to 146 micrograms/mg cell protein). Concomitantly, media triglycerides nearly doubled (31 to 51 micrograms/mg). Incorporation of [3H]glyceride into cellular and media triglyceride also rose. However, levels of apoproteins A-I, B, C-III3, and E in cells and media were unchanged. The increasing amounts of triglycerides in media were present in larger particles, as demonstrated on gel permeation chromatography. The elution profiles of apoproteins B, C-III3, and E were altered in that a greater proportion of the apoproteins eluted with larger particles. Similar results were obtained when hepatocytes were preloaded with increasing amounts of FFA over 12 h and analyses of cells and media were carried out 8 and 22 h after removal of fatty acids from the media. During loading of cells, accumulation of cellular triglycerides was directly related to media FFA concentrations. During unloading, triglyceride secretory rates were related to cellular triglyceride levels. At higher triglyceride secretory rates larger particles were secreted and a greater proportion of apoproteins was associated with the larger particles, but total amounts of apoproteins in the system did not change. These data lead us to suggest that enhanced rates of apoprotein synthesis need not occur in the response to acute changes in hepatic lipid transport, rather, increased secretion of lipid is brought about by augmented intracellular lipid apoprotein association.     

Effect of infused volatile fatty acids and caseinate on milk composition and coagulation in dairy cows

Milk protein secretion is changed by increasing the proportion of energy, mainly as propionic acid, or the availability of AA. Whether associative effects exist between energy nature and protein amounts is unknown. Therefore, ruminal isoenergetic infusions of low or high propionate mixtures were combined factorially with duodenal infusion of sodium caseinate or control. Four ruminally and duodenally fistulated Holstein cows were used. The diet was limited and consisted of 70% forage and 30% concentrate. Caseinate infusion increased milk yield and protein and casein contents and decreased milk fat content; curd yields and coagulation properties of milk were improved. The infusion of propionic acid caused a large increase in rumen propionate. Milk yield tended to decrease, and milk fat decreased, but protein, casein, and curd yields were unchanged; milk-coagulating properties were improved. No interaction existed between energy and protein amounts. Alteration of VFA had little effect on milk composition, but increasing the protein supply to the duodenum increased milk protein.     

Hypothalamic mediated action of free fatty acid on growth hormone secretion in sheep

Experimental data suggest that elevated FFA levels play a leading role in the impaired GH secretion in obesity and may therefore contribute to the maintenance of overweight. GH has a direct lipolytic effect on adipose tissue; in turn, FFA elevation markedly reduces GH secretion. This suggests the existence of a classical endocrine feedback loop between FFA and GH secretion. However, the FFA mechanism of action is not yet understood. The involvement of somatostatin (SRIH) is controversial, and in vitro experiments suggest a direct effect of FFA on the pituitary. In sheep it is possible to collect hypophysial portal blood and quantify SRIH secretion in hypophysial portal blood under physiological conscious and unstressed conditions. In this study we determined the effects of FFA (Intralipid and heparin) infusion on peripheral GH and portal SRIH levels in intact rams chronically implanted with perihypophysial cannula and in rams actively immunized against SRIH to further determine SRIH-mediated FFA effects on GH axis. Immediately after initiation of Intralipid infusion, we observed a marked increase in the FFA concentration (2160 +/- 200 vs. 295 +/- 28 nmol/ml; P < 0.01) as well as a significant decrease in basal GH secretion (1.8 +/- 0.1 vs. 2.5 +/- 0.3 ng/ml; P < 0.05) and a drastic reduction of the GH response to i.v. GH-releasing hormone injection (4.8 +/- 0.7 ng/ml in FFA group vs. 35.8 +/- 9.7 ng/ml in saline group; P < 0.01). No change in plasma insulin-like growth factor I levels was observed. During the first 2 h of infusion, the GH decrease observed was concomitant with a significant increase in portal SRIH levels (22.1 +/- .2 vs. 13 +/- 1.6 pg/ml; P < 0.01). In rams actively immunized against SRIH, the effect of FFA on basal GH secretion was biphasic. During the first 90 min of infusion, the decrease in GH induced by FFA was significantly blunted in rams actively immunized against SRIH (57 +/- 9% for immunized rams vs. 23.5 +/- 2.5% for control rams). This corresponds to the period of increased SRIH portal levels. After this first 90-min period, no difference was seen between control and immunized rams. Our results show that FFA exert their inhibitory action on the GH axis at both pituitary and hypothalamic levels, the latter mainly during the first 90 min, through increased SRIH secretion.     

Direct effects of growth hormone (GH)-releasing hexapeptide (GHRP-6) and GH-releasing factor (GRF) on GH secretion from cultured porcine somatotropes

Growth hormone (GH)-releasing hexapeptide (GHRP-6) belongs to the expanding family of synthetic GH secretagogues (GHSs). Previous studies have shown that non-peptidyl GHRP-6 analogues stimulate GH release in vivo in pigs, and interact synergistically with GH-releasing factor (GRF), but its direct effects on porcine somatotropes have not been addressed hitherto. In the present study, we have evaluated the response of cultured porcine pituitary cells to GHRP-6, and its interaction with GRF and somatostatin (SRIF). Secretory response of somatotropes was assessed by using two distinct techniques. GH released by monolayer cell cultures was evaluated by enzyme immunoassay, whereas that secreted by individual somatotropes was measured by immunodensitometry using a cell blotting assay. Our results demonstrate that both GHRP-6 and GRF stimulated GH release from monolayer cultures at doses equal to or above 10(-9) M. Use of cell immunoblot assay demonstrated that, like GRF, the hexapeptide acts directly upon porcine somatotropes to exert its action. Moreover, regardless of the technique applied, combined administration of GHRP-6 (10(-6) or 10(-9) M) and GRF (10(-8) M) resulted in an additive, but not synergistic, stimulatory GH response. Finally, SRIF (10(-7) M) inhibited the stimulatory effect of GHRP-6 alone or in combination with GRF. These results indicate that GHRP-6 directly and effectively stimulates GH secretion from porcine somatotropes in vitro, and acts additively when coadministered with GRF. Therefore, the synergistic stimulatory effect of GHSs and GRF reported in vivo in this species might require additional factors that are lacking in the in vitro situation.     

Effect of opioid blockade on insulin and growth hormone (GH) secretion in patients with polycystic ovary syndrome: the heterogeneity of impaired GH secretion is related to both obesity and hyperinsulinism

Amplitude-coded color Doppler sonography (ACD) has become an useful adjunct to gray-scale US and conventional color Doppler sonography (CD) for the assessment of vascular diseases and pathologic conditions that might affect or alter tissue vascularization or perfusion. Basically, all US units that generate conventional color Doppler information through autocorrelation technique are capable of displaying ACD. This technique is also referred to as power Doppler, amplitude-mode color Doppler US, color Doppler energy (CDE), or US angiography. Amplitude-coded color Doppler sonography has already emerged as a valuable adjunct to conventional CD, particularly for evaluating flow in parts of the body where CD signal is weak because of slow flow, small blood vessels, or both.     

Hepatic secretion of VLDL fatty acids during stimulated lipogenesis in men

Fatty acids (FA) that are utilized for triglyceride (TG) synthesis in the liver and principally from two sources: FA synthesized de novo in the liver and preformed FA. We have measured the contribution from the two sources to very low density lipoprotein (VLDL) TG synthesis individually for palmitate, oleate, stearate, and linoleate (approximately 98% of the total FA of VLDL TG (VLDL TGFA)) by isotopomer analysis. Five healthy men were studied in the basal state, and 1 (day 1) and 4 days (day 4) after the start of a hypercaloric carbohydrate-enriched diet (approximately 2.5 times energy expenditure). The secretion of de novo palmitate was increased 15- and 43-fold after 1 and 4 days of hyperalimentation (2.6+/-1.2 (basal state), 40.8+/-20.0 (day 1), and 113.3+/-42.0 micromol/kg per d (day 4)). Even though 4 days of hyperalimentation increased the secretion of de novo stearate 43-fold and de novo oleate 70-fold (stearate; 0.2+/-0.2 (basal), 8.6+/-3.3 micromol/kg per d (day 4), oleate; 0.4+/-0.4 (basal), 28.2+/-12.7 micromol/kg per d (day 4)), palmitate accounted for 75-85% of all the de novo VLDL TGFA. One day of carbohydrate hyperalimentation tended to decrease the secretion while 4 days increased the secretion of all preformed FA in VLDL TG. The rate of secretion of preformed palmitate and oleate were almost identical (palmitate; 80.2+/-22.2 (basal), 45.1+/-23.8 (day 1), and 256.2+/-74.1 micromol/kg per d (day 4), oleate; 95.2+/-22.8 (basal), 46.2+/-24.2 (day 1), and 356.8+/-74.1 micromol/kg per d (day 4)) and collectively these two FA accounted for 80-90% of the secretion from the preformed source. Palmitate is the predominant product of acute and prolonged carbohydrate mediated lipogenesis in the human liver. The pathway of further elongation and subsequent desaturation of de novo synthesized palmitate to generate stearate and oleate is inducible but, quantitatively, of minor significance in hepatic lipogenesis.     

Effect of cis-unsaturated fatty acids on cellular oxidant stress in macrophage tumor (AK-5) cells in vitro

Cis-unsaturated fatty acids (c-UFAs) induced decreased survival of macrophage tumor (AK-5) cells in vitro. The cytotoxic action of c-UfAs was associated with an increase in free radical generation and lipid peroxidation process. In addition, exposure of AK-5 cells to various c-UFAs for a short period (1 h) decreased the cellular concentrations of anti-oxidants: superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione reductase, glutathione and vitamin E. However, prolonged (24 h) exposure of AK-5 cells to c-UFAs enhanced the levels of SOD with little or no change in the concentrations of catalase, glutathione peroxidase and glutathione reductase. These results indicate that c-UFAs can enhance free radical generation and lower the concentrations of various anti-oxidants in the tumor cells which may explain the cytotoxic action of c-UFAs.     

Proportions of volatile fatty acids in relation to the chemical composition of feeds based on grass silage

This experiment was designed to quantify the relationships between feed chemistry and the proportions of rumen volatile fatty acids (VFA) across a wide range of feedstuffs. In an experiment using 11 rumencannulated sheep, 16 test feeds were fed at three different inclusion rates in rations that were based on grass silage. The 17 periods of the experiment were each 14 d long. Eight rumen samples were taken every 24 h on d 13 and 14 of each period from which the mean daily proportions of VFA were derived. The effects of an increase in the proportion of test feed in the total feed on proportions of VFA were significant. The observed proportions of VFA were related to the chemical composition of the total feed by principal component regression. The inclusion of the amount of feed offered and the ratio of test feed to total feed in these regressions did not improve their precision; these terms were not significant. The significant terms in the regressions were crude protein, starch, sugar, and cellulose (calculated by difference). The R2 values achieved for the regressions between acetate, propionate, and butyrate (molar proportions) and feed composition were 77.5, 68.0, and 87.3%, respectively. These regressions provided an apparently robust basis for predicting molar proportions of VFA from feed chemistry in feeds based on grass silage.     

Effects of level and type of energy source (volatile fatty acids or glucose) on milk yield, composition and coagulating properties in dairy cows

Four fistulated Holstein cows were arranged in a 4 x 4 Latin square design to study the effects of level and type of energy source on milk yield and composition. Treatments consisted of a basal diet fed alone (low energy treatment) or with 3.3 Mcal of net energy for lactation from extra nutrients perfused either into the rumen (either propionic acid or a mixture of volatile fatty acids) or into the duodenum (glucose). Increasing the energy input without changing the volatile fatty acid profile improved milk yield and slightly increased milk protein and fat yields. Compared with the isoenergetic mixture of volatile fatty acids, both propionic acid and glucose infusions significantly decreased fat content (-4.5 g/kg) and yields (respectively, -111 and -160 g/d), but affected fatty acid proportion and yield differently (more elongation process and less C18 with glucose infusion). Protein yield was slightly increased by propionic acid infusion but not by glucose because of the counterbalanced effects on milk yield (-1.3 kg/d) and protein content (1.5 g/kg). The coagulating properties of milk were directly linked to variations in protein, casein and mineral contents. In conclusion, propionic acid or glucose scarcely affected milk protein content, but induced a similar decrease in milk fat content probably through different metabolic pathways.     

Stimulation by urocortin of growth hormone (GH) secretion in GH-producing human pituitary adenoma cells

Urocortin (Ucn) possesses high homology with CRH and is considered to be a ligand to type-2 CRH receptor. We investigated the effect of Ucn on hormone release from cultured GH-producing human pituitary adenoma cells in vitro. GH-producing human pituitary adenoma cells were superfused on a Sephadex G-25 column. Both Ucn (10 nM) and CRH (10 nM) elicited an increase in GH release from the pituitary adenoma cells in one patient with acromegaly. In contrast, GH release from the pituitary adenoma cells was stimulated by Ucn but not by CRH in the other patient with acromegaly. These preliminary findings suggest that type-2 CRH receptors are expressed in some population of GH-producing human pituitary adenoma cells and that Ucn might be involved in GH secretion from tumorous tissues in patients with acromegaly.     

Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat

We asked whether the well known starvation-induced impairment of glucose-stimulated insulin secretion (GSIS) seen in isolated rat pancreas preparations also applies in vivo. Accordingly, fed and 18-24-h-fasted rats were subjected to an intravenous glucose challenge followed by a hyperglycemic clamp protocol, during which the plasma-insulin concentration was measured. Surprisingly, the acute (5 min) insulin response was equally robust in the two groups. However, after infusion of the antilipolytic agent, nicotinic acid, to ensure low levels of plasma FFA before the glucose load, GSIS was essentially ablated in fasted rats, but unaffected in fed animals. Maintenance of a high plasma FFA concentration by coadministration of Intralipid plus heparin to nicotinic acid-treated rats (fed or fasted), or further elevation of the endogenous FFA level in nonnicotinic acid-treated fasted animals by infusion of etomoxir (to block hepatic fatty acid oxidation), resulted in supranormal GSIS. The in vivo findings were reproduced in studies with the perfused pancreas from fed and fasted rats in which GSIS was examined in the absence and presence of palmitate. The results establish that in the rat, the high circulating concentration of FFA that accompanies food deprivation is a sine qua non for efficient GSIS when a fast is terminated. They also serve to underscore the powerful interaction between glucose and fatty acids in normal beta cell function and raise the possibility that imbalances between the two fuels in vivo could have pathological consequences.     

The measurement of production rates of volatile fatty acids in the caecum of the conscious rabbit

1. The decrease in specific radioactivity of individual volatile fatty acids (VFA) after a single injection of tracer was monitored. The results obtained indicated the occurrence of a first-order process. 2. Regression analysis indicated the high flux of VFA through the caecal pool, equivalent to 30% of the maintenance energy requirement of the animal. 3. Interconversion of VFA was monitored, and results indicated substantial synthesis of butyric acid from acetic acid. 4. Results were obtained from animals on two dietary regimens, and these were compared with results reported for the other species.     

Growth hormone (GH) secretion from human lymphocytes is up-regulated by GH, but not affected by insulin-like growth factor-I

Regulation of GH secretion from phytohemagglutinin (PHA)-stimulated lymphocytes was investigated in six normal subjects. Peripheral blood mononuclear cells were incubated with PHA (10 micrograms/mL) in the presence of various amounts of recombinant human GH (0-100 ng/L) and/or recombinant human insulin-like growth factor-I (0-1000 micrograms/L), and the secreted GH was measured by a highly sensitive enzyme immunoassay. PHA-stimulated lymphocytes secreted immunoreactive GH in all subjects (13.6 +/- 2.4 ng/L). Exogenous GH up-regulated the GH secretion in a dose-dependent manner, while IGF-I did not affect either basal GH secretion or the up-regulation by exogenous GH. These findings suggest a difference in the regulation of GH secretion between endocrine and immune systems.     

磷对GH169合金组织性能的影响

对不同磷含量5炉GH169(IN718)合金进行力学性能测试及显微组织分析,结果表明,磷具有\     

Effect of essential and nonessential fatty acids in complex mixture on fatty acid composition of liver lipids

Linoleate, linolenate, arachidonate, docosahexenoate and six other fatty acids were major components of 24 ester preparations fed as 5% of the diet for 60 days to groups of male white rats. The experiment was designed so as to provide that all major fatty acid components were independent of each other in the sense that the intake of each was poorly correlated with the intake of any of the others. Fatty acid compositions of liver lipids were determined and were related to the composition of the diet lipids. Linolenate and docosahexaenoate contents of diet and tissue revealed the same relationships reported previously from experiments in which individual pure acid esters were added to a fat-free diet. Linoleate, when fed in lipid mixtures, was more effective in raising the linoleate concentration in liver lipids than when fed alone, but this increase did not change the shape of the dose-response curve or the estimated nutritional requirement. Large amounts of fish oil in the diet tended to depress the arachidonate concentration in tissue lipids.     

Effect of self-determined intravenous infusion of hypertonic NaCl on Na appetite of sheep.

The time delay between a rapid, systemically produced change in sodium balance and a change of voluntary sodium intake was examined in sodium-deficient sheep with a parotid fistula. They were trained to barpress to replace a daily sodium deficit of 300–500 mmol. During basal conditions on different days, each delivery to a drinking cup consisted of either a small or a large amount of NaHCO? solution. In the experimental situation, the small amount of NaHCO? was delivered to the cup, but total sodium delivered was made to equal that of the large amount by automatic concurrent infusion of hypertonic NaCl iv with each delivery to the cup. As a control, the concurrent iv infusion was .15 M NaCl, which had little influence on sodium balance. A significant difference in the cumulative number of deliveries between the hypertonic and isotonic NaCl infusion conditions occurred by 10–20 min. It is concluded that systemic injections of hypertonic NaCl are effective within 10–20 min in reducing the sodium appetite of Na-depleted animals. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)