scholarly journals Changes in energy metabolism and respiration in different tracheal narrowing in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yael Segev ◽  
Haiat Nujedat ◽  
Eden Arazi ◽  
Mohammad H. Assadi ◽  
Ariel Tarasiuk
Keyword(s):  
Airway Obstruction ◽  
Behavior Management ◽  
Elevated Serum ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Metabolic Physiology ◽  
Obstructive Sleep ◽  
Phosphorylated Akt ◽  
Osa Treatment ◽  
Respiratory Homeostasis

AbstractWhy obstructive sleep apnea (OSA) treatment does not completely restore healthy metabolic physiology is unclear. In rats, the need for respiratory homeostasis maintenance following airway obstruction (AO) is associated with a loss of thermoregulation and abnormal metabolic physiology that persists following successful obstruction removal. Here, we explored the effect of two different types of tracheal narrowing, i.e., AO and mild airway obstruction (mAO), and its removal on respiratory homeostasis and metabolic physiology. We show that after ten weeks, mAO vs. AO consumes sufficient energy that is required to maintain respiratory homeostasis and thermoregulation. Obstruction removal was associated with largely irreversible increased feeding associated with elevated serum ghrelin, hypothalamic growth hormone secretagogue receptor 1a, and a phosphorylated Akt/Akt ratio, despite normalization of breathing and energy requirements. Our study supports the need for lifestyle eating behavior management, in addition to endocrine support, in order to attain healthy metabolic physiology in OSA patients.

scholarly journals Irreversible metabolic abnormalities following chronic upper airway loading

SLEEP ◽  
2019 ◽  
Vol 42 (12) ◽  
Author(s):  
Mohammad H Assadi ◽  
Yael Segev ◽  
Ariel Tarasiuk
Keyword(s):  
Body Temperature ◽  
Energy Expenditure ◽  
Airway Obstruction ◽  
Neuropeptide Y ◽  
Upper Airway ◽  
Upper Airway Obstruction ◽  
Endocrine Regulation ◽  
Brown Adipose ◽  
Obstructive Sleep ◽  
Respiratory Homeostasis

Abstract Study Objectives Treatment of obstructive sleep apnea increases obesity risk by an unclear mechanism. Here, we explored the effects of upper airway obstruction and its removal on respiratory homeostasis, energy expenditure, and feeding hormones during the sleep/wake cycle from weaning to adulthood. Methods The tracheas of 22-day-old rats were narrowed, and obstruction removal was performed on post-surgery day 14. Energy expenditure, ventilation, and hormone-regulated feeding were analyzed during 49 days before and after obstruction. Results Energy expenditure increased and body temperature decreased in upper airway obstruction and was only partially recovered in obstruction removal despite normalization of airway resistance. Increased energy expenditure was associated with upregulation of ventilation. Decreased body temperature was associated with decreased brown adipose tissue uncoupling protein 1 level, suppressed energy expenditure response to norepinephrine, and decreased leptin level. Upper airway obstructed animals added less body weight, in spite of an increase in food intake, due to elevated hypothalamic orexin and neuropeptide Y and plasma ghrelin. Animals who underwent obstruction removal fed more due to an increase in hypothalamic neuropeptide Y and plasma ghrelin. Conclusions The need to maintain respiratory homeostasis is associated with persistent abnormal energy metabolism and hormonal regulation of feeding. Surgical treatment per se may not be sufficient to correct energy homeostasis, and endocrine regulation of feeding may have a larger effect on weight change.

scholarly journals Cannabinoid-Induced Conditioned Place Preference, Intravenous Self-Administration, and Behavioral Stimulation Influenced by Ghrelin Receptor Antagonism in Rats

2021 ◽  
Vol 22 (5) ◽  
pp. 2397
Author(s):  
Chrysostomos Charalambous ◽  
Tereza Havlickova ◽  
Marek Lapka ◽  
Nina Puskina ◽  
Romana Šlamberová ◽  
...  
Keyword(s):  
Conditioned Place Preference ◽  
Fixed Ratio ◽  
Place Preference ◽  
Self Administration ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ghrelin Receptor ◽  
Addiction Therapy ◽  
Significant Efficacy ◽  
Lever Pressing

Cannabis/cannabinoids are widely used for recreational and therapy purposes, but their risks are largely disregarded. However, cannabinoid-associated use disorders and dependence are alarmingly increasing and an effective treatment is lacking. Recently, the growth hormone secretagogue receptor (GHSR1A) antagonism was proposed as a promising mechanism for drug addiction therapy. However, the role of GHS-R1A and its endogenous ligand ghrelin in cannabinoid abuse remains unclear. Therefore, the aim of our study was to investigate whether the GHS-R1A antagonist JMV2959 could reduce the tetrahydrocannabinol (THC)-induced conditioned place preference (CPP) and behavioral stimulation, the WIN55,212-2 intravenous self-administration (IVSA), and the tendency to relapse. Following an ongoing WIN55,212-2 self-administration, JMV2959 3 mg/kg was administered intraperitoneally 20 min before three consequent daily 120-min IVSA sessions under a fixed ratio FR1, which significantly reduced the number of the active lever-pressing, the number of infusions, and the cannabinoid intake. Pretreatment with JMV2959 suggested reduction of the WIN55,212-2-seeking/relapse-like behavior tested in rats on the twelfth day of the forced abstinence period. On the contrary, pretreatment with ghrelin significantly increased the cannabinoid IVSA as well as enhanced the relapse-like behavior. Co-administration of ghrelin with JMV2959 abolished/reduced the significant efficacy of the GHS-R1A antagonist in the cannabinoid IVSA. Pretreatment with JMV2959 significantly and dose-dependently reduced the manifestation of THC-induced CPP. The THC-CPP development was reduced after the simultaneous administration of JMV2959 with THC during conditioning. JMV2959 also significantly reduced the THC-induced behavioral stimulation in the LABORAS cage. Our findings suggest that GHS-R1A importantly participates in the rewarding/reinforcing effects of cannabinoids.

807 Diagnostic Pathways of Patients Authorized for Obstructive Sleep Apnea Testing and Treatment: A Retrospective Claims Analysis

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A315-A315
Author(s):  
Binh Nguyen ◽  
Aliza Gordon ◽  
Stefanida Blake ◽  
Lakshmi Kalluri ◽  
Winnie Chi ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Laboratory Testing ◽  
Diagnostic Testing ◽  
Prior Authorization ◽  
Home Test ◽  
Home Testing ◽  
Obstructive Sleep ◽  
Osa Treatment ◽  
Diagnostic Pathways ◽  
Lab Test

Abstract Introduction Obstructive Sleep Apnea (OSA) has been shown to reduce health-related quality of life and is associated with cardiovascular disease and other negative health outcomes. However, many patients with suspected OSA are never tested, thereby remaining undiagnosed and untreated. In this study, we explore the diagnostic pathways and eventual treatment of individuals with suspected OSA. Methods We conducted a retrospective, observational study, linking claims and prior authorization data of a large, geographically diverse health insurer’s commercial and Medicare Advantage members. Our sample included adults with suspected OSA and no prior OSA history, whose diagnostic testing had been approved through prior authorization (N=75,011). Using a 3-month time window following authorization, we searched for a claim to match the authorized service (home or laboratory sleep testing). We also looked for subsequent prior authorization for OSA treatment (Positive Airway Pressure (PAP) or oral appliance) and corresponding claims for those treatments within the 3-month authorization window. Results Among the study sample (N=75,011), 40,002 (53.3%) had home testing only, 17,319 (23.1%) had laboratory testing only, and 6,053 (8.1%) had a home test followed by a laboratory test. Only 476 (0.6%) had a home test after the date of a lab test. 11,161 individuals (14.9%) did not complete any sleep test. Of the 63,850 individuals with any sleep testing, 39,062 (61.2%) received prior authorization for initiating OSA treatment, and 36,158 (92.6%) of them had a corresponding claim for treatment. Conclusion One in eight adults with suspected OSA for whom diagnostic testing was authorized did not undergo testing; among those who tested, home testing was most common. While it is clinically appropriate to follow a negative home test with a lab test since a home test cannot rule out OSA (only confirm it), the study notes that a significant number of those with a home test require follow-up laboratory testing. Together, this represents an opportunity for reducing barriers to testing and improvement in home testing technology. Support (if any) This study was funded by Anthem, Inc.

scholarly journals Growth hormone secretagogue receptor in dopamine neurons controls appetitive and consummatory behaviors towards high-fat diet in ad-libitum fed mice

2020 ◽  
Vol 119 ◽  
pp. 104718
Author(s):  
María Paula Cornejo ◽  
Franco Barrile ◽  
Daniela Cassano ◽  
Julieta Paola Aguggia ◽  
Guadalupe García Romero ◽  
...  
Keyword(s):  
Growth Hormone ◽  
High Fat Diet ◽  
Dopamine Neurons ◽  
High Fat ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ad Libitum

Novel Isoxazole Carboxamides as Growth Hormone Secretagogue Receptor (GHS-R) Antagonists.

ChemInform ◽  
2005 ◽  
Vol 36 (4) ◽  
Author(s):  
Bo Liu ◽  
Gang Liu ◽  
Zhili Xin ◽  
Michael D. Serby ◽  
Hongyu Zhao ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue

scholarly journals Intraportal Infusion of Ghrelin Could Inhibit Glucose-Stimulated GLP-1 Secretion by Enteric Neural Net in Wistar Rat

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Xiyao Zhang ◽  
Wensong Li ◽  
Ping Li ◽  
Manli Chang ◽  
Xu Huang ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Food Intake ◽  
Portal Vein ◽  
Wistar Rat ◽  
Inhibitory Effect ◽  
Neural Net ◽  
Incretin Effect ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Intraportal Infusion

As a regulator of food intake and energy metabolism, the role of ghrelin in glucose metabolism is still not fully understood. In this study, we determined the in vivo effect of ghrelin on incretin effect. We demonstrated that ghrelin inhibited the glucose-stimulated release of glucagon-like peptide-1 (GLP-1) when infused into the portal vein of Wistar rat. Hepatic vagotomy diminished the inhibitory effect of ghrelin on glucose-stimulated GLP-1 secretion. In addition, phentolamine, a nonselective α receptor antagonist, could recover the decrease of GLP-1 release induced by ghrelin infusion. Pralmorelin (an artificial growth hormone release peptide) infusion into the portal vein could also inhibit the glucose-stimulated release of GLP-1. And growth hormone secretagogue receptor antagonist, [D-lys3]-GHRP-6, infusion showed comparable increases of glucose stimulated GLP-1 release compared to ghrelin infusion into the portal vein. The data showed that intraportal infusion of ghrelin exerted an inhibitory effect on GLP-1 secretion through growth hormone secretagogue receptor 1α (GHS1α receptor), which indicated that the downregulation of ghrelin secretion after food intake was necessary for incretin effect. Furthermore, our results suggested that the enteric neural net involved hepatic vagal nerve and sympathetic nerve mediated inhibition effect of ghrelin on incretin effect.

scholarly journals Cortistatin Is Not a Somatostatin Analogue but Stimulates Prolactin Release and Inhibits GH and ACTH in a Gender-Dependent Fashion: Potential Role of Ghrelin

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4800-4812 ◽  
Author(s):  
José Córdoba-Chacón ◽  
Manuel D. Gahete ◽  
Ana I. Pozo-Salas ◽  
Antonio J. Martínez-Fuentes ◽  
Luis de Lecea ◽  
...  
Keyword(s):  
Metabolic Phenotype ◽  
Somatostatin Analogue ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ancestral Gene ◽  
Ghrelin Receptor ◽  
Physiological Relevance

Cortistatin (CST) and somatostatin (SST) evolve from a common ancestral gene and share remarkable structural, pharmacological, and functional homologies. Although CST has been considered as a natural SST-analogue acting through their shared receptors (SST receptors 1–5), emerging evidence indicates that these peptides might in fact exert unique roles via selective receptors [e.g. CST, not SST, binds ghrelin receptor growth hormone secretagogue receptor type 1a (GHS-R1a)]. To determine whether the role of endogenous CST is different from SST, we characterized the endocrine-metabolic phenotype of male/female CST null mice (cort−/−) at hypothalamic-pituitary-systemic (pancreas-stomach-adrenal-liver) levels. Also, CST effects on hormone expression/secretion were evaluated in primary pituitary cell cultures from male/female mice and female primates (baboons). Specifically, CST exerted an unexpected stimulatory role on prolactin (PRL) secretion, because both male/female cort−/− mice had reduced PRL levels, and CST treatment (in vivo and in vitro) increased PRL secretion, which could be blocked by a GHS-R1a antagonist in vitro and likely relates to the decreased success of female cort−/− in first-litter pup care at weaning. In contrast, CST inhibited GH and adrenocorticotropin-hormone axes in a gender-dependent fashion. In addition, a rise in acylated ghrelin levels was observed in female cort−/− mice, which were associated with an increase in stomach ghrelin/ghrelin O-acyl transferase expression. Finally, CST deficit uncovered a gender-dependent role of this peptide in the regulation of glucose-insulin homeostasis, because male, but not female, cort−/− mice developed insulin resistance. The fact that these actions are not mimicked by SST and are strongly gender dependent offers new grounds to investigate the hitherto underestimated physiological relevance of CST in the regulation of physiological/metabolic processes.

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