scholarly journals Impact of Growth Hormone Receptor Blockade on Substrate Metabolism during Fasting in Healthy Subjects

2009 ◽  
Vol 94 (11) ◽  
pp. 4524-4532 ◽  
Author(s):  
Louise Moller ◽  
Helene Norrelund ◽  
Niels Jessen ◽  
Allan Flyvbjerg ◽  
Steen B. Pedersen ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Free Fatty Acids ◽  
Protein Metabolism ◽  
Healthy Subjects ◽  
Receptor Blockade ◽  
Substrate Metabolism ◽  
Gh Receptor ◽  
Basal Period ◽  
Igf I

Context: Experimental studies in GH-deficient patients and in healthy subjects receiving somatostatin-infusion suggest that GH is an important regulator of substrate metabolism during fasting. These models may not adequately reflect the selective effects of GH, and GH receptor (GHR) blockade offers a new model to define the metabolic role of GH. Objective: The aim of this study was to investigate the impact of GHR blockade on substrate metabolism and insulin sensitivity during fasting. Design: We conducted a randomized, placebo-controlled, crossover study in 10 healthy young men. Intervention: After 36 h of fasting with saline or pegvisomant (GHR blockade), the subjects were studied during a 4-h basal period and 2.5-h hyperinsulinemic euglycemic clamp. Main Outcome: We measured whole-body and forearm glucose, lipid, and protein metabolism, peripheral insulin sensitivity, and acyl and desacyl ghrelin. Results: GHR blockade significantly suppressed circulating free fatty acids (1226 ± 83 vs. 1074 ± 65 μmol/liter; P = 0.03) and ketone bodies (3080 ± 271 vs. 2015 ± 235 μmol/liter; P ≤ 0.01), as well as forearm uptake of free fatty acids (0.341 ± 0.150 vs. 0.004 ± 0.119 μmol/100 ml · min; P < 0.01) and lipid oxidation (1.3 ± 0.1 vs. 1.2 ± 0.1 mg/kg · min; P = 0.03) in the basal period. By contrast, IGF-I levels in either serum or peripheral tissues were not impacted by GHR blockade, and protein metabolism was also unaffected. Basal glucose levels were elevated by GHR blockade, but insulin sensitivity was similar; this was associated with an increased acyl/desacyl ghrelin ratio. Conclusion: GHR blockade, without changes in circulating or tissue IGF-I levels, selectively suppresses lipid mobilization and oxidation after short-term fasting. This supports the notion that stimulation of lipolysis is a primary and important effect of GH. GH receptor blockade during fasting in healthy subjects suppresses lipid metabolism without a change in insulin sensitivity or protein metabolism.

scholarly journals Serum secreted frizzled-related protein 5 in relation to insulin sensitivity and its regulation by insulin and free fatty acids

Endocrine ◽  
2021 ◽  
Author(s):  
Marta Rydzewska ◽  
Agnieszka Nikołajuk ◽  
Natalia Matulewicz ◽  
Magdalena Stefanowicz ◽  
Monika Karczewska-Kupczewska
Keyword(s):  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Free Fatty Acids ◽  
Wnt Signaling Pathway ◽  
Normal Weight ◽  
Healthy Population ◽  
Related Protein ◽  
Heparin Infusion ◽  
Male Subjects ◽  
Contradictory Data

Abstract Purpose Secreted frizzled-related protein 5 (SFRP5) is an adipokine, which acts as an inhibitor of noncanonical WNT signaling pathway. It has been suggested to exert anti-inflammatory and insulin-sensitizing effects, however, contradictory data has also been reported. The aim of this study was to assess serum SFRP5 concentration in a young healthy population in relation to insulin sensitivity and its regulation by hyperinsulinemia and/or serum free fatty acids (FFA) elevation. Methods We examined 150 healthy subjects (83 normal-weight and 67 overweight/obese). Insulin sensitivity (M) was measured with hyperinsulinemic-euglycemic clamp. In 20 male subjects, clamp was prolonged to 6 h and after 1 week another clamp with the concurrent Intralipid/heparin infusion was performed. Independent group of 10 male subjects received infusions of Intralipid/heparin or saline in 1-week interval. Results Baseline SFRP5 was lower in the overweight/obese group (p = 0.01) and was positively associated with M (r = 0.23, p = 0.006) and serum adiponectin (r = 0.55, p < 0.001) and negatively with BMI (r = −0.18, p = 0.03). In multiple regression analysis, adiponectin was independently associated with SFRP5. Insulin infusion resulted in a decrease in serum SFRP5, both at 120′ (p = 0.02) and 360′ (p = 0.031). This effect was not observed during the clamp with Intralipid/heparin as well as during Intralipid/heparin alone or saline infusions. Conclusions The relation between SFRP5 and insulin sensitivity is mainly dependent on adiponectin. FFA abolish a decrease in circulating SFRP5 caused by insulin, but Intralipid/heparin infusion alone does not regulate SFRP5 concentration. Insulin seems to be more important factor in the regulation of circulating SFRP5 levels than FFA.

Elevated plasma free fatty acids decrease basal protein synthesis, but not the anabolic effect of leucine, in skeletal muscle

2006 ◽  
Vol 291 (3) ◽  
pp. E666-E674 ◽  
Author(s):  
Charles H. Lang
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Protein Synthesis ◽  
Free Fatty Acids ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Short Term ◽  
Lipid Infusion ◽  
Igf I ◽  
Plasma Ffas

Elevations in free fatty acids (FFAs) impair glucose uptake in skeletal muscle. However, there is no information pertaining to the effect of elevated circulating lipids on either basal protein synthesis or the anabolic effects of leucine and insulin-like growth factor I (IGF-I). In chronically catheterized conscious rats, the short-term elevation of plasma FFAs by the 5-h infusion of heparin plus Intralipid decreased muscle protein synthesis by ∼25% under basal conditions. Lipid infusion was associated with a redistribution of eukaryotic initiation factor (eIF)4E from the active eIF4E·eIF4G complex to the inactive eIF4E·4E-BP1 complex. This shift was associated with a decreased phosphorylation of eIF4G but not 4E-BP1. Lipid infusion did not significantly alter either the total amount or phosphorylation state of mTOR, TSC2, S6K1, or the ribosomal protein S6 under basal conditions. In control rats, oral leucine increased muscle protein synthesis. This anabolic response was not impaired by lipid infusion, and no defects in signal transduction pathways regulating translation initiation were detected. In separate rats that received a bolus injection of IGF-I, lipid infusion attenuated the normal redistribution of eIF4E from the active to inactive complex and largely prevented the increased phosphorylation of 4E-BP1, eIF4G, S6K1, and S6. This IGF-I resistance was associated with enhanced Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1). These data indicate that the short-term elevation of plasma FFAs impairs basal protein synthesis in muscle by altering eIF4E availability, and this defect may be related to impaired phosphorylation of eIF4G, not 4E-BP1. Moreover, hyperlipidemia impairs IGF-I action but does not produce leucine resistance in skeletal muscle.

scholarly journals Inhibition of Insulin Sensitivity by Free Fatty Acids Requires Activation of Multiple Serine Kinases in 3T3-L1 Adipocytes

2004 ◽  
Vol 18 (8) ◽  
pp. 2024-2034 ◽  
Author(s):  
Zhanguo Gao ◽  
Xiaoying Zhang ◽  
Aamir Zuberi ◽  
Daniel Hwang ◽  
Michael J. Quon ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Free Fatty Acids ◽  
Serine Kinases

Insulin sensitivity and big ET-1 conversion to ET-1 after ETA- or ETB-receptor blockade in humans

2002 ◽  
Vol 93 (6) ◽  
pp. 2112-2121 ◽  
Author(s):  
Gunvor Ahlborg ◽  
Jonas Lindström
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Healthy Subjects ◽  
Receptor Blockade ◽  
Receptor Stimulation ◽  
Renal Vasoconstriction ◽  
Arterial Blood ◽  
Etb Receptor

Cardiovascular diseases are characterized by insulin resistance and elevated endothelin (ET)-1 levels. Furthermore, ET-1 induces insulin resistance. To elucidate this mechanism, six healthy subjects were studied during a hyperinsulinemic euglycemic clamp during infusion of (the ET-1 precursor) big ET-1 alone or after ETA- or ETB-receptor blockade. Insulin levels rose after big ET-1 with or without the ETB antagonist BQ-788 ( P < 0.05) but were unchanged after the ETA antagonist BQ-123 + big ET-1. Infused glucose divided by insulin fell after big ET-1 with or without BQ-788 ( P < 0.05). Insulin and infused glucose divided by insulin values were normalized by ETA blockade. Mean arterial blood pressure rose during big ET-1 with or without BQ-788 ( P < 0.001) but was unchanged after BQ-123. Skeletal muscle, splanchnic, and renal blood flow responses to big ET-1 were abolished by BQ-123. ET-1 levels rose after big ET-1 ( P< 0.01) in a similar way after BQ-123 or BQ-788, despite higher elimination capacity after ETA blockade. In conclusion, ET-1-induced reduction in insulin sensitivity and clearance as well as splanchnic and renal vasoconstriction are ETA mediated. ETA-receptor stimulation seems to inhibit the conversion of big ET-1 to ET-1.

Effects of free fatty acids, growth hormone and growth hormone receptor blockade on serum ghrelin levels in humans

2007 ◽  
Vol 66 (5) ◽  
pp. 641-645 ◽  
Author(s):  
Lars C. Gormsen ◽  
Charlotte Nielsen ◽  
Jakob Gjedsted ◽  
Signe Gjedde ◽  
Esben Thyssen Vestergaard ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Growth Hormone ◽  
Free Fatty Acids ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Receptor Blockade ◽  
Serum Ghrelin

scholarly journals Application of Sebum Lipidomics to Biomarkers Discovery in Neurodegenerative Diseases

Metabolites ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 819
Author(s):  
Stefania Briganti ◽  
Mauro Truglio ◽  
Antonella Angiolillo ◽  
Salvatore Lombardo ◽  
Deborah Leccese ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Vitamin E ◽  
Observational Study ◽  
Neurodegenerative Diseases ◽  
Free Fatty Acids ◽  
Healthy Subjects ◽  
Skin Surface ◽  
Biosynthetic Pathways ◽  
Simultaneous Component Analysis ◽  
Lipid Species

Lipidomics is strategic in the discovery of biomarkers of neurodegenerative diseases (NDDs). The skin surface lipidome bears the potential to provide biomarker candidates in the detection of pathological processes occurring in distal organs. We investigated the sebum composition to search diagnostic and, possibly, prognostic, biomarkers of Alzheimer’s disease (AD) and Parkinson’s disease (PD). The observational study included 64 subjects: 20 characterized as “probable AD with documented decline”, 20 as “clinically established PD”, and 24 healthy subjects (HS) of comparable age. The analysis of sebum by GCMS and TLC retrieved the amounts (µg) of 41 free fatty acids (FFAs), 7 fatty alcohols (FOHs), vitamin E, cholesterol, squalene, and total triglycerides (TGs) and wax esters (WEs). Distributions of sebum lipids in NDDs and healthy conditions were investigated with multivariate ANOVA-simultaneous component analysis (ASCA). The deranged sebum composition associated with the PD group showed incretion of most composing lipids compared to HS, whereas only two lipid species (vitamin E and FOH14:0) were discriminant of AD samples and presented lower levels than HS sebum. Thus, sebum lipid biosynthetic pathways are differently affected in PD and AD. The characteristic sebum bio-signatures detected support the value of sebum lipidomics in the biomarkers search in NDDs.

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