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Short-Term Effects of Growth Hormone on Lipolysis, Glucose and Amino Acid Metabolism Assessed in Serum and Microdialysate of Healthy Young Men.
Krebs, A, Baum, A, Doerfer, J, Gempel, K, Wurm, M, Brichta, C, Sass, JO, Winkler, K, Schwab, KO
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2020;(12):819-826
Abstract
OBJECTIVE We investigated direct effects of a therapeutic growth hormone dose on lipolysis, glucose and amino acid metabolism. METHODS This crossover microdialysis trial involved six healthy male volunteers receiving single subcutaneous injections of both growth hormone (0.035 mg/kg) and placebo (0.9% sodium chloride). The investigation comprised three test days with standard diet. The first day served for adaptation, the second and third one for determining study data during 9 night hours with or without growth hormone. Abdominal subcutaneous microdialysate and blood were continuously collected and forwarded to a separate room next door where hourly taken samples were centrifuged and frozen until analysed. RESULTS Growth hormone achieved the peak serum level after 3 h followed by a plateau-like course for the next 6 h. Glycerol in microdialysate started to rise 2 h following growth hormone injection achieving significance compared to placebo after 9 h (P<0.05). Serum glycerol increased 4 h after growth hormone administration achieving significance after 6 h (P<0.05). Glucose and amino acid concentrations showed neither in microdialysate nor in serum significant differences between growth hormone and placebo. Serum values of insulin and C-peptide revealed no significant difference between growth hormone and placebo. SUMMARY AND CONCLUSION As the result of a high single subcutaneous dose of GH, persistent lipolysis can be shown in continuously collected microdialysate and blood, but no indication for gluconeogenesis or protein anabolism.
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Insulin-mediated suppression of lipolysis in adipose tissue and skeletal muscle of obese type 2 diabetic men and men with normal glucose tolerance.
Jocken, JW, Goossens, GH, Boon, H, Mason, RR, Essers, Y, Havekes, B, Watt, MJ, van Loon, LJ, Blaak, EE
Diabetologia. 2013;(10):2255-65
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Abstract
AIMS/HYPOTHESIS Impaired regulation of lipolysis and accumulation of lipid intermediates may contribute to obesity-related insulin resistance and type 2 diabetes mellitus. We investigated insulin-mediated suppression of lipolysis in abdominal subcutaneous adipose tissue (AT) and skeletal muscle (SM) of obese men with normal glucose tolerance (NGT) and obese type 2 diabetic men. METHODS Eleven NGT men and nine long-term diagnosed type 2 diabetic men (7 ± 1 years), matched for age (58 ± 2 vs 62 ± 2 years), BMI (31.4 ± 0.6 vs 30.5 ± 0.6 kg/m(2)) and [Formula: see text] (28.9 ± 1.5 vs 29.5 ± 2.4 ml kg(-1) min(-1)) participated in this study. Interstitial glycerol concentrations in AT and SM were assessed using microdialysis during a 1 h basal period and a 6 h stepwise hyperinsulinaemic-euglycaemic clamp (8, 20 and 40 mU m(-2) min(-1)). AT and SM biopsies were collected to investigate underlying mechanisms. RESULTS Hyperinsulinaemia suppressed interstitial SM glycerol concentrations less in men with type 2 diabetes (-7 ± 6%, -13 ± 9% and -27 ± 9%) compared with men with NGT (-21 ± 7%, -38 ± 8% and -53 ± 8%) (p = 0.014). This was accompanied by increased circulating fatty acid and glycerol concentrations, a lower glucose infusion rate (21.8 ± 3.1 vs 30.5 ± 2.0 μmol kg body weight(-1) min(-1); p < 0.05), higher hormone-sensitive lipase (HSL) serine 660 phosphorylation, increased saturated diacylglycerol (DAG) lipid species in the muscle membrane and increased protein kinase C (PKC) activation in type 2 diabetic men vs men with NGT. No significant differences in insulin-mediated reduction in AT interstitial glycerol were observed between groups. CONCLUSIONS/INTERPRETATION Our results suggest that a blunted insulin-mediated suppression of SM lipolysis may promote the accumulation of membrane saturated DAG, aggravating insulin resistance, at least partly mediated by PKC. This may represent an important mechanism involved in the progression of insulin resistance towards type 2 diabetes. TRIAL REGISTRATION ClinicalTrials.gov NCT01680133.
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Injection lipolysis for reduction of saddlebag trochanteric bulges--half-side controlled pilot study.
Kopera, D, Horejsi, R, Werner, S, Moeller, R
Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. 2008;(4):287-90
Abstract
BACKGROUND Phosphatidylcholine, a lecithin extracted from soybeans can reduce serum cholesterol to some extent. Intravenous use may prevent fat embolism in polytrauma patients. When injected intralesionally in a formulation containing also deoxycholate and ethanol it is supposed to act as "fat burner" to reduce undesired fat deposits; there is little evidence-based scientific support for this indication. OBJECTIVE To evaluate the capability of phosphatidylcholine + deoxycholate + ethanol (PPC/DC/E) to reduce body fat with a half-side pilot study for the reduction of saddlebag trochanteric bulges. METHODS PPC/DC/E was injected into the right posterior trochanteric areas three times at weeks 0, 3 and 6. Treatment areas and the same regions of the contralateral side as a control were evaluated by sonography. Tape measurements were taken and the thickness of the subcutaneous adipose tissue (SAT) was measured with an optical device (Lipometer) at baseline and at week 8 and week 20 (2 and 14 weeks after completing therapy). RESULTS In this half-side trial, no significant reduction of subcutaneous fat was achieved after three treatments with PPC/DC/E when compared to the untreated side.Transient inflammatory reactions occurred in all patients. LIMITATIONS Only the commercially available formulation containing the three components was tested. CONCLUSION The off-label use of PPC/DC/E as a "fat burner" did not produce measurable reduction of undesired trochanteric fat deposits.
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Blunted lipolysis and fatty acid oxidation during moderate exercise in HIV-infected subjects taking HAART.
Cade, WT, Reeds, DN, Mittendorfer, B, Patterson, BW, Powderly, WG, Klein, S, Yarasheski, KE
American journal of physiology. Endocrinology and metabolism. 2007;(3):E812-9
Abstract
The protease inhibitor (PI) ritonavir (RTV) has been associated with elevated resting lipolytic rate, hyperlipidemia, and insulin resistance/glucose intolerance. The purpose of this study was to examine relationships between lipolysis and fatty acid (FA) oxidation during rest, moderate exercise and recovery, and measures of insulin sensitivity/glucose tolerance and fat redistribution in HIV-positive subjects taking RTV (n=12), HAART but no PI (n=10), and HIV-seronegative controls (n=10). Stable isotope tracers [1-(13)C]palmitate and [1,1,2,3,3-(2)H5]glycerol were continuously infused with blood and breath collection during 1-h rest, 70-min submaximal exercise (50% VO2 peak), and 1-h recovery. Body composition was evaluated using DEXA, MRI, and MRS, and 2-h oral glucose tolerance tests with insulin monitoring were used to evaluate glucose tolerance and insulin resistance. Lipolytic and FA oxidation rates were similar during rest and recovery in all groups; however, they were lower during moderate exercise in both HIV-infected groups [glycerol Ra: HIV+RTV 5.1+/-1.2 vs. HIV+no PI 5.9+/-2.8 vs. Control 7.4+/-2.2 micromol.kg fat-free mass (FFM)-1.min-1; palmitate oxidation: HIV+RTV 1.6+/-0.8 vs. HIV+no PI 1.6+/-0.8 vs. Control 2.5+/-1.7 micromol.kg FFM.min, P<0.01]. Fasting and orally-challenged glucose and insulin values were similar among groups. Lipolytic and FA oxidation rates were blunted during moderate exercise in HIV-positive subjects taking HAART. Lower FA oxidation during exercise was primarily due to impaired plasma FA oxidation, with a minor contribution from lower nonplasma FA oxidation. Regional differences in adipose tissue lipolysis during rest and moderate exercise may be important in HIV and warrant further study.
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Angiotensin II-induced effects on adipose and skeletal muscle tissue blood flow and lipolysis in normal-weight and obese subjects.
Goossens, GH, Blaak, EE, Saris, WH, van Baak, MA
The Journal of clinical endocrinology and metabolism. 2004;(6):2690-6
Abstract
The present study was designed to investigate the effects of angiotensin II (Ang II) on adipose and skeletal muscle tissue blood flow and lipolysis in normal-weight and obese subjects using the microdialysis technique. Microdialysis probes were placed in the abdominal sc adipose tissue left and right from the umbilicus and in the gastrocnemius muscle of both legs in eight normal-weight and eight obese men. Probes were consecutively perfused with 1.0 nM Ang II, 1.0 microM Ang II, and 1.0 microM Ang II + 48 microM hydralazine or with Ringer solution (control). Ethanol and glycerol concentrations in the dialysate were measured as an indicator of local blood flow and lipolysis, respectively. Ang II caused an increase in ethanol outflow/inflow ratio, compared with baseline values both in adipose tissue (average of both groups, Ang 1.0 nM: 0.03 +/- 0.01, P = 0.02; Ang 1.0 microM: 0.05 +/- 0.01, P < 0.01) and muscle (average of both groups, Ang 1.0 nM: 0.02 +/- 0.01, P = 0.09; Ang 1.0 microM: 0.04 +/- 0.01, P = 0.01), indicating a decrease in local blood flow. These effects were not significantly different in obese and normal-weight subjects. The decrease in local blood flow was accompanied by unchanged interstitial glycerol concentrations in adipose tissue (except during the supraphysiological dose) and skeletal muscle, suggesting that Ang II inhibits lipolysis in both tissues. Thus, the present data suggest that Ang II decreases local blood flow in a dose-dependent manner and inhibits lipolysis both in adipose and skeletal muscle tissue. These effects were not significantly different in obese and normal-weight subjects in both tissues.
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Preferential stimulation of abdominal subcutaneous lipolysis after prednisolone exposure in humans.
Gravholt, CH, Dall, R, Christiansen, JS, Møller, N, Schmitz, O
Obesity research. 2002;(8):774-81
Abstract
OBJECTIVE The role of cortisol in the regulation of lipolysis is not clear. This study was undertaken to explore whether a standard dose of prednisolone for 1 week would influence lipolysis in abdominal and femoral tissue. RESEARCH METHODS AND PROCEDURES We used the microdialysis technique, the forearm technique, and indirect calorimetry, in the fasting state, after 1 week of treatment with prednisolone (30 mg daily) or placebo. Eight healthy young men (age: 25 +/- 3 years; height: 181 +/- 1 cm; body mass index [BMI]: 23.3 +/- 0.7 kg/m(2)) were studied. RESULTS Treatment with prednisolone induced insulin resistance (Homeostasis Model Assessment index: placebo vs. prednisolone: 7.15 +/- 1.63 vs. 17.00 +/- 14.26, p = 0.03), hyperinsulinemia (p = 0.01), and hyperglucagonemia (p = 0.001), whereas growth hormone concentrations were unaffected. Abdominal adipose tissue interstitial glycerol was increased during treatment with prednisolone in the face of significant hyperinsulinemia, although it barely reached statistical significance (p = 0.06). At the femoral adipose tissue depot, no difference in lipolysis was found. Arterial and venous free fatty acids (FFA) were comparable in the two situations, whereas the arteriovenous difference across the forearm was significantly decreased during treatment with prednisolone, indicating increased uptake, or decreased release of FFA. Energy expenditure (p = 0.3), respiratory quotient (p = 0.9), glucose oxidation (p = 0.9), lipid oxidation (p = 1.0), and protein oxidation (p = 0.1) were unaltered on the 2 study days. DISCUSSION Short-term treatment with a standard dose of corticosteroids induces increased abdominal adipose tissue lipolysis, as well as hyperinsulinemia, hyperglucagonemia, and insulin resistance.
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Effects of cortisol on lipolysis and regional interstitial glycerol levels in humans.
Djurhuus, CB, Gravholt, CH, Nielsen, S, Mengel, A, Christiansen, JS, Schmitz, OE, Møller, N
American journal of physiology. Endocrinology and metabolism. 2002;(1):E172-7
Abstract
Cortisol's effects on lipid metabolism are controversial and may involve stimulation of both lipolysis and lipogenesis. This study was undertaken to define the role of physiological hypercortisolemia on systemic and regional lipolysis in humans. We investigated seven healthy young male volunteers after an overnight fast on two occasions by means of microdialysis and palmitate turnover in a placebo-controlled manner with a pancreatic pituitary clamp involving inhibition with somatostatin and substitution of growth hormone, glucagon, and insulin at basal levels. Hydrocortisone infusion increased circulating concentrations of cortisol (888 +/- 12 vs. 245 +/- 7 nmol/l). Interstitial glycerol concentrations rose in parallel in abdominal (327 +/- 35 vs. 156 +/- 30 micromol/l; P = 0.05) and femoral (178 +/- 28 vs. 91 +/- 22 micromol/l; P = 0.02) adipose tissue. Systemic [(3)H]palmitate turnover increased (165 +/- 17 vs. 92 +/- 24 micromol/min; P = 0.01). Levels of insulin, glucagon, and growth hormone were comparable. In conclusion, the present study unmistakably shows that cortisol in physiological concentrations is a potent stimulus of lipolysis and that this effect prevails equally in both femoral and abdominal adipose tissue.
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Does glucagon have a lipolytic effect?
Ranganath, L, Schaper, F, Gama, R, Morgan, L
Clinical endocrinology. 2001;(1):125-6