scholarly journals Mouse Spexin: (III) Differential Regulation by Glucose and Insulin in Glandular Stomach and Functional Implication in Feeding Control

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuan Chen ◽  
Mulan He ◽  
Martina M. L. Lei ◽  
Wendy K. W. Ko ◽  
Chengyuan Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Glucose Uptake ◽  
Cell Model ◽  
Atp Synthesis ◽  
Glandular Stomach ◽  
Transcript Expression ◽  
Channel Activity ◽  
Mucosal Cells ◽  
Feeding Control

Spexin (SPX), a neuropeptide with diverse functions, is a novel satiety factor in fish models and its role in feeding control has been recently confirmed in mammals. In mouse, food intake was shown to trigger SPX expression in glandular stomach with parallel rise in serum SPX and these SPX signals could inhibit feeding via central actions within the hypothalamus. However, the mechanisms for SPX regulation by food intake are still unclear. To examine the role of insulin signal caused by glucose uptake in SPX regulation, the mice were IP injected with glucose and insulin, respectively. In this case, serum SPX was elevated by glucose but not altered by insulin. Meanwhile, SPX transcript expression in the glandular stomach was up-regulated by glucose but the opposite was true for insulin treatment. Using in situ hybridization, the differential effects on SPX gene expression were located in the gastric mucosa of glandular stomach. Co-injection experiments also revealed that glucose stimulation on serum SPX and SPX mRNA expressed in glandular stomach could be blocked by insulin. In gastric mucosal cells prepared from glandular stomach, the opposite effects on SPX transcript expression by glucose and insulin could still be noted with similar blockade of the stimulatory effects of glucose by insulin. In this cell model, SPX gene expression induced by glucose was mediated by glucose uptake via GLUT, ATP synthesis by glycolysis/respiratory chain, and subsequent modulation of KATP channel activity, but the voltage-sensitive Ca2+ channels were not involved. The corresponding inhibition by insulin, however, was mediated by PI3K/Akt, MEK1/2/ERK1/2, and P38MAPK cascades coupled to insulin receptor but not IGF-1 receptor. Apparently, glucose uptake in mice can induce SPX expression in the glandular stomach through ATP synthesis via glucose metabolism and subsequent modification of KATP channel activity, which may contribute to SPX release into circulation to act as the satiety signal after food intake. The insulin rise caused by glucose uptake, presumably originated from the pancreas, may serve as a negative feedback to inhibit the SPX response by activating MAPK and PI3K/Akt pathways in the stomach.

scholarly journals Spexin as a Satiety Factor in Mouse via Regulatory Actions Within the Hypothalamus

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A57-A58
Author(s):  
Matthew K H Wong ◽  
Yuan Chen ◽  
Mulan He ◽  
Chengyuan Lin ◽  
Zhaoxiang Bian ◽  
...  
Keyword(s):  
Food Intake ◽  
Food Consumption ◽  
Leptin Receptor ◽  
Feedback Inhibition ◽  
Mammalian Species ◽  
Cell Types ◽  
Glandular Stomach ◽  
Transcript Expression ◽  
Ghrelin Receptor

Abstract Spexin (SPX) is a pleiotropic peptide with highly conserved protein sequence from fish to mammals and its biological actions are mediated by GalR2/GalR3 receptors expressed in target tissues. Recently, SPX was found to be a novel satiety factor in fish models but whether the peptide has a similar function in mammals is still unknown. Using the mouse as a model for mammalian species, the functional role of SPX in feeding control and the mechanisms involved were investigated. After food intake, serum SPX could be up-regulated in mice with parallel elevations of transcript expression and tissue content of SPX in the glandular stomach but not in other tissues examined. As revealed by immunostaining, food intake also intensified SPX signals in different cell types within the gastric mucosa of glandular stomach. Furthermore, IP injection of SPX was effective in reducing food consumption with parallel drops in transcript expression of NPY, AgRP, NPY type 5 receptor (NPY5R) and ghrelin receptor (GHSR) in the hypothalamus, and these inhibitory effects could be blocked by GalR3 but not GalR2 antagonism. In agreement with the central actions of SPX, similar inhibition on food intake and hypothalamic expression of NPY, AgRP, NPY5R and GHSR could be observed with ICV injection of SPX. In the same study, parallel rises of transcript expression of leptin receptor (LepR) and melanocortin 4 receptor (MC4R) were also observed in the hypothalamus. These findings, taken together, suggest that the role of SPX as a satiety factor is well-conserved in the mouse. Probably, food consumption can induce SPX production in glandular stomach and contribute to the postprandial rise of SPX in circulation. Through GalR3 activation, this SPX signal can act within the hypothalamus to trigger feedback inhibition on food intake by differential modulation of the feeding regulators (NPY & AgRP) and their receptors (NPY5R, GHSR, LepR & MC4R) involved in the feeding circuitry of the brain.

Involvement of central microsomal prostaglandin E synthase-1 in IL-1β-induced anorexia

2006 ◽  
Vol 25 (3) ◽  
pp. 485-492 ◽  
Author(s):  
E. Pecchi ◽  
M. Dallaporta ◽  
S. Thirion ◽  
C. Salvat ◽  
F. Berenbaum ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Molecular Mechanisms ◽  
Sickness Behavior ◽  
Prostaglandin E ◽  
Concomitant Reduction ◽  
Intracerebroventricular Injections ◽  
Feeding Control ◽  
Significant Health

In response to infection or inflammation, individuals develop a set of symptoms referred to as sickness behavior, which includes a decrease in food intake. The characterization of the molecular mechanisms underlying this hypophagia remains critical, because chronic anorexia may represent a significant health risk. Prostaglandins (PGs) constitute an important inflammatory mediator family whose levels increase in the brain during inflammatory states, and their involvement in inflammatory-induced anorexia has been proposed. The microsomal PGE synthase (mPGES)-1 enzyme is involved in the last step of PGE2 biosynthesis, and its expression is stimulated by proinflammatory agents. The present study attempted to determine whether an upregulation of mPGES-1 gene expression may account for the immune-induced anorexic behavior. We focused our study on mPGES-1 expression in the hypothalamus and dorsal vagal complex, two structures strongly activated during peripheral inflammation and involved in the regulation of food intake. We showed that mPGES-1 gene expression was robustly upregulated in these structures after intraperitoneal and intracerebroventricular injections of anorexigenic doses of IL-1β. This increase was correlated with the onset of anorexia. The concomitant reduction in food intake and central mPGES-1 gene upregulation led us to test the feeding behavior of mice lacking mPGES-1 during inflammation. Interestingly, IL-1β failed to decrease food intake in mPGES-1−/− mice, although these animals developed anorexia in response to a PGE2 injection. Taken together, our results demonstrate that mPGES-1, which is strongly upregulated during inflammation in central structures involved in feeding control, is essential for immune anorexic behavior and thus may constitute a potential therapeutic target.

Anti-Diabetic and Angio-Protective Effect of Guluronic Acid (G2013) as a New Nonsteroidal Anti-Inflammatory Drug in the Experimental Model of Diabetes

2020 ◽  
Vol 20 (3) ◽  
pp. 446-452
Author(s):  
Seyed S. Mortazavi-Jahromi ◽  
Shahab Alizadeh ◽  
Mohammad H. Javanbakht ◽  
Abbas Mirshafiey
Keyword(s):  
Gene Expression ◽  
Blood Glucose ◽  
Food Intake ◽  
Experimental Model ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Diabetic Control ◽  
The Body ◽  
Sprague Dawley ◽  
Guluronic Acid

Background: This study aimed to investigate the effects of guluronic acid (G2013) on blood sugar, insulin, and gene expression profile of oxLDL receptors (SR-A, CD36, LOX-1, and CD68) in the experimental model of diabetes. Methods: 18 Sprague Dawley rats were randomly assigned to three groups of healthy control, diabetic control, and G2013 group. Diabetes was induced through intraperitoneal (IP) injection of 60 mg/kg streptozotocin. The subjects were IP treated with 25 mg/kg of G2013 per day for 28 days. The body weight, food intake, fasting blood glucose and insulin were measured. In addition, the expression of mentioned genes was investigated through quantitative real-time PCR. Results: The data showed that the final weight increased significantly in the G2013-treated subjects compared to the diabetic control (p < 0.05). The results indicated that final food intake significantly reduced in the G2013-treated subjects compared to the diabetic control (p < 0.05). The study findings also suggested that the final fasting blood glucose significantly reduced in the G2013-treated group, whereas the final fasting serum insulin level significantly increased in this group compared to the diabetic control (p < 0.05). Moreover, the gene expression levels of SR-A, CD36, LOX-1, and CD68 in the G2013 group significantly reduced compared to the diabetic control (p < 0.05). Conclusion: This study showed that G2013, could reduce blood glucose and increase insulin levels and reduce the gene expression level of oxLDL receptors. In addition, it may probably play an important role in reducing the severity of diabetes-induced inflammatory symptoms.

scholarly journals LMO3 reprograms visceral adipocyte metabolism during obesity

2021 ◽  
Author(s):  
Gabriel Wagner ◽  
Anna Fenzl ◽  
Josefine Lindroos-Christensen ◽  
Elisa Einwallner ◽  
Julia Husa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Visceral Adipose Tissue ◽  
Tissue Expansion ◽  
Oxidative Capacity ◽  
Glut4 Translocation ◽  
Mitochondrial Oxidative Capacity ◽  
Visceral Adipose

Abstract Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. We recently identified LIM domain only 3 (LMO3) in human mature visceral adipocytes; however, its function in these cells is currently unknown. The aim of this study was to determine the potential involvement of LMO3-dependent pathways in the modulation of key functions of mature adipocytes during obesity. Based on a recently engineered hybrid rAAV serotype Rec2 shown to efficiently transduce both brown adipose tissue (BAT) and white adipose tissue (WAT), we delivered YFP or Lmo3 to epididymal WAT (eWAT) of C57Bl6/J mice on a high-fat diet (HFD). The effects of eWAT transduction on metabolic parameters were evaluated 10 weeks later. To further define the role of LMO3 in insulin-stimulated glucose uptake, insulin signaling, adipocyte bioenergetics, as well as endocrine function, experiments were conducted in 3T3-L1 adipocytes and newly differentiated human primary mature adipocytes, engineered for transient gain or loss of LMO3 expression, respectively. AAV transduction of eWAT results in strong and stable Lmo3 expression specifically in the adipocyte fraction over a course of 10 weeks with HFD feeding. LMO3 expression in eWAT significantly improved insulin sensitivity and healthy visceral adipose tissue expansion in diet-induced obesity, paralleled by increased serum adiponectin. In vitro, LMO3 expression in 3T3-L1 adipocytes increased PPARγ transcriptional activity, insulin-stimulated GLUT4 translocation and glucose uptake, as well as mitochondrial oxidative capacity in addition to fatty acid oxidation. Mechanistically, LMO3 induced the PPARγ coregulator Ncoa1, which was required for LMO3 to enhance glucose uptake and mitochondrial oxidative gene expression. In human mature adipocytes, LMO3 overexpression promoted, while silencing of LMO3 suppressed mitochondrial oxidative capacity. LMO3 expression in visceral adipose tissue regulates multiple genes that preserve adipose tissue functionality during obesity, such as glucose metabolism, insulin sensitivity, mitochondrial function, and adiponectin secretion. Together with increased PPARγ activity and Ncoa1 expression, these gene expression changes promote insulin-induced GLUT4 translocation, glucose uptake in addition to increased mitochondrial oxidative capacity, limiting HFD-induced adipose dysfunction. These data add LMO3 as a novel regulator improving visceral adipose tissue function during obesity. Key messages LMO3 increases beneficial visceral adipose tissue expansion and insulin sensitivity in vivo. LMO3 increases glucose uptake and oxidative mitochondrial activity in adipocytes. LMO3 increases nuclear coactivator 1 (Ncoa1). LMO3-enhanced glucose uptake and mitochondrial gene expression requires Ncoa1.

scholarly journals Glucokinase Regulates Reproductive Function, Glucocorticoid Secretion, Food Intake, and Hypothalamic Gene Expression

Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1928-1932 ◽  
Author(s):  
Xue-jun Yang ◽  
Jason Mastaitis ◽  
Tooru Mizuno ◽  
Charles V. Mobbs
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Reproductive Function

Contraction-related stimuli regulate GLUT4 traffic in C2C12-GLUT4myc skeletal muscle cells

2010 ◽  
Vol 298 (5) ◽  
pp. E1058-E1071 ◽  
Author(s):  
Wenyan Niu ◽  
Philip J. Bilan ◽  
Shuhei Ishikura ◽  
Jonathan D. Schertzer ◽  
Ariel Contreras-Ferrat ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Surface ◽  
Glucose Uptake ◽  
Nicotinic Acetylcholine Receptors ◽  
Cell Model ◽  
Cytosolic Calcium ◽  
Atpase Inhibitor ◽  
Cellular Models ◽  
Compound C

Muscle contraction stimulates glucose uptake acutely to increase energy supply, but suitable cellular models that faithfully reproduce this complex phenomenon are lacking. To this end, we have developed a cellular model of contracting C2C12 myotubes overexpressing GLUT4 with an exofacial myc-epitope tag (GLUT4 myc) and explored stimulation of GLUT4 traffic by physiologically relevant agents. Carbachol (an acetylcholine receptor agonist) induced a gain in cell surface GLUT4 myc that was mediated by nicotinic acetylcholine receptors. Carbachol also activated AMPK, and this response was sensitive to the contractile myosin ATPase inhibitor N-benzyl- p-toluenesulfonamide. The gain in surface GLUT4 myc elicited by carbachol or by the AMPK activator 5-amino-4-carboxamide-1 β-ribose was sensitive to chemical inhibition of AMPK activity by compound C and partially reduced by siRNA-mediated knockdown of AMPK catalytic subunits or LKB1. In addition, the carbachol-induced gain in cell surface GLUT4 myc was partially sensitive to chelation of intracellular calcium with BAPTA-AM. However, the carbachol-induced gain in cell surface GLUT4 myc was not sensitive to the CaMKK inhibitor STO-609 despite expression of both isoforms of this enzyme and a rise in cytosolic calcium by carbachol. Therefore, separate AMPK- and calcium-dependent signals contribute to mobilizing GLUT4 in response to carbachol, providing an in vitro cell model that recapitulates the two major signals whereby acute contraction regulates glucose uptake in skeletal muscle. This system will be ideal to further analyze the underlying molecular events of contraction-regulated GLUT4 traffic.

Gene expression profiling of cranial sensory ganglia that transmit food intake stimuli

BioFactors ◽  
2004 ◽  
Vol 21 (1-4) ◽  
pp. 15-18 ◽  
Author(s):  
Ichiro Matsumoto ◽  
Shugo Nakamura ◽  
Yasufumi Emori ◽  
Soichi Arai ◽  
Keiko Abe
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Sensory Ganglia ◽  
Cranial Sensory Ganglia
Sign in / Sign up

Export Citation Format

Share Document