scholarly journals The receptive function of hypothalamic and brainstem centres to hormonal and nutrient signals affecting energy balance

2012 ◽  
Vol 71 (4) ◽  
pp. 463-477 ◽  
Author(s):  
Thomas Riediger
Keyword(s):  
Energy Balance ◽  
Peptide Yy ◽  
Late Onset ◽  
Area Postrema ◽  
Body Weight Loss ◽  
Dependent Manner ◽  
Experimental Conditions ◽  
Combination Treatments ◽  
Hypothalamic Arcuate Nucleus ◽  
Glucagon Like Peptide 1

The hypothalamic arcuate nucleus (ARC) and the area postrema (AP) represent targets for hormonal and metabolic signals involved in energy homoeostasis, e.g. glucose, amylin, insulin, leptin, peptide YY (PYY), glucagon-like peptide 1 (GLP-1) and ghrelin. Orexigenic neuropeptide Y expressing ARC neurons are activated by food deprivation and inhibited by feeding in a nutrient-dependent manner. PYY and leptin also reverse or prevent fasting-induced activation of the ARC. Interestingly, hypothalamic responses to fasting are blunted in different models of obesity (e.g. diet-induced obesity (DIO) or late-onset obesity). The AP also responds to feeding-related signals. The pancreatic hormone amylin acts via the AP to control energy intake. Amylin-sensitive AP neurons are also glucose-responsive. Furthermore, diet-derived protein attenuates amylin responsiveness suggesting a modulation of AP sensitivity by macronutrient supply. This review gives an overview of the receptive function of the ARC and the AP to hormonal and nutritional stimuli involved in the control of energy balance and the possible implications in the context of obesity. Collectively, there is consistency between the neurophysiological actions of these stimuli and their effects on energy homoeostasis under experimental conditions. However, surprisingly little progress has been made in the development of effective pharmacological approaches against obesity. A promising way to improve effectiveness involves combination treatments (e.g. amylin/leptin agonists). Hormonal alterations (e.g. GLP-1 and PYY) are also considered to mediate body weight loss observed in obese patients receiving bariatric surgery. The effects of hormonal and nutritional signals and their interactions might hold the potential to develop poly-mechanistic therapeutic strategies against obesity.

scholarly journals GPR119 Regulates Murine Glucose Homeostasis Through Incretin Receptor-Dependent and Independent Mechanisms

Endocrinology ◽  
2010 ◽  
Vol 152 (2) ◽  
pp. 374-383 ◽  
Author(s):  
Grace Flock ◽  
Dianne Holland ◽  
Yutaka Seino ◽  
Daniel J. Drucker
Keyword(s):  
Insulin Secretion ◽  
Gastric Emptying ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Peptide Yy ◽  
Cell Receptor ◽  
Dependent Manner ◽  
Glucagon Like Peptide 1

Abstract G protein-coupled receptor 119 (GPR119) was originally identified as a β-cell receptor. However, GPR119 activation also promotes incretin secretion and enhances peptide YY action. We examined whether GPR119-dependent control of glucose homeostasis requires preservation of peptidergic pathways in vivo. Insulin secretion was assessed directly in islets, and glucoregulation was examined in wild-type (WT), single incretin receptor (IR) and dual IR knockout (DIRKO) mice. Experimental endpoints included plasma glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide YY. Gastric emptying was assessed in WT, Glp1r−/−, DIRKO, Glp2r−/−, and GPR119−/− mice treated with the GPR119 agonist AR231453. AR231453 stimulated insulin secretion from WT and DIRKO islets in a glucose-dependent manner, improved glucose homeostasis, and augmented plasma levels of GLP-1, GIP, and insulin in WT and Gipr−/−mice. In contrast, although AR231453 increased levels of GLP-1, GIP, and insulin, it failed to lower glucose in Glp1r−/− and DIRKO mice. Furthermore, AR231453 did not improve ip glucose tolerance and had no effect on insulin action in WT and DIRKO mice. Acute GPR119 activation with AR231453 inhibited gastric emptying in Glp1r−/−, DIRKO, Glp2r−/−, and in WT mice independent of the Y2 receptor (Y2R); however, AR231453 did not control gastric emptying in GPR119−/− mice. Our findings demonstrate that GPR119 activation directly stimulates insulin secretion from islets in vitro, yet requires intact IR signaling and enteral glucose exposure for optimal control of glucose tolerance in vivo. In contrast, AR231453 inhibits gastric emptying independent of incretin, Y2R, or Glp2 receptors through GPR119-dependent pathways. Hence, GPR119 engages multiple complementary pathways for control of glucose homeostasis.

scholarly journals PACAP intraperitoneal treatment suppresses appetite and food intake via PAC1 receptor in mice by inhibiting ghrelin and increasing GLP-1 and leptin

2015 ◽  
Vol 309 (10) ◽  
pp. G816-G825 ◽  
Author(s):  
John P. Vu ◽  
Deepinder Goyal ◽  
Leon Luong ◽  
Suwan Oh ◽  
Ravneet Sandhu ◽  
...  
Keyword(s):  
Food Intake ◽  
Feeding Behavior ◽  
Peptide Yy ◽  
Dark Phase ◽  
Dependent Manner ◽  
Pac1 Receptor ◽  
Intraperitoneal Treatment ◽  
Regulate Food Intake ◽  
Feeding Parameters ◽  
Glucagon Like Peptide 1

Pituitary adenylate cyclase-activating peptide (PACAP) is expressed within the gastroenteric system, where it has profound physiological effects. PACAP was shown to regulate food intake and thermogenesis centrally; however, PACAP peripheral regulation of appetite and feeding behavior is unknown. Therefore, we studied PACAP's effect on appetite and food intake control by analyzing feeding behavior and metabolic hormones in PAC1-deficient (PAC1−/−) and age-matched wild-type (WT) mice intraperitoneally injected with PACAP1–38 or PACAP1–27 before the dark phase of feeding. Food intake and feeding behavior were analyzed using the BioDAQ system. Active ghrelin, glucagon-like peptide-1 (GLP-1), leptin, peptide YY, pancreatic polypeptide, and insulin were measured following PACAP1–38 administration in fasted WT mice. PACAP1–38/PACAP1–27 injected into WT mice significantly decreased in a dose-dependent manner cumulative food intake and reduced bout and meal feeding parameters. Conversely, PACAP1–38 injected into PAC1−/− mice failed to significantly change food intake. Importantly, PACAP1–38 reduced plasma levels of active ghrelin compared with vehicle in WT mice. In PAC1−/− mice, fasting levels of active ghrelin, GLP-1, insulin, and leptin and postprandial levels of active ghrelin and insulin were significantly altered compared with levels in WT mice. Therefore, PAC1 is a novel regulator of appetite/satiety. PACAP1–38/PACAP1–27 significantly reduced appetite and food intake through PAC1. In PAC1−/− mice, the regulation of anorexigenic/orexigenic hormones was abolished, whereas active ghrelin remained elevated even postprandially. PACAP significantly reduced active ghrelin in fasting conditions. These results establish a role for PACAP via PAC1 in the peripheral regulation of appetite/satiety and suggest future studies to explore a therapeutic use of PACAP or PAC1 agonists for obesity treatment.

scholarly journals GIP Receptor Agonism Attenuates GLP-1 Receptor Agonist Induced Nausea and Emesis in Preclinical Models

2021 ◽  
Author(s):  
Tito Borner ◽  
Caroline E. Geisler ◽  
Samantha M. Fortin ◽  
Richard Cosgrove ◽  
Jorge Alsina-Fernandez ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Body Weight Loss ◽  
Diabetes Patient ◽  
Obesity And Diabetes ◽  
Nausea And Emesis ◽  
Glucagon Like Peptide 1 ◽  
Cellular Phenotypes

Glucagon-like peptide-1 receptor (GLP-1R) agonists decrease body weight and improve glycemic control in obesity and diabetes. Patient compliance and maximal efficacy of GLP-1 therapeutics are limited by side effects including nausea and emesis. In three different species (i.e., mice, rats, and musk shrews), we show that glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling blocks emesis and attenuates illness behaviors elicited by GLP-1R activation, while maintaining reduced food intake, body weight loss, and improved glucose tolerance. The area postrema and nucleus tractus solitarius (AP/NTS) of the hindbrain are required for food intake and body weight suppression by GLP-1R ligands and processing of emetic stimuli. Utilizing single-nuclei RNA-sequencing, we identified the cellular phenotypes of AP/NTS GIPR- and GLP-1R-expressing cells on distinct populations of inhibitory and excitatory neurons, with the greatest expression of GIPR in GABAergic neurons. This work suggests that combinatorial pharmaceutical targeting of GLP-1R and GIPR will increase efficacy in treating obesity and diabetes by reducing nausea and vomiting.

scholarly journals GIP Receptor Agonism Attenuates GLP-1 Receptor Agonist Induced Nausea and Emesis in Preclinical Models

2021 ◽  
Author(s):  
Tito Borner ◽  
Caroline E. Geisler ◽  
Samantha M. Fortin ◽  
Richard Cosgrove ◽  
Jorge Alsina-Fernandez ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Body Weight Loss ◽  
Diabetes Patient ◽  
Obesity And Diabetes ◽  
Nausea And Emesis ◽  
Glucagon Like Peptide 1 ◽  
Cellular Phenotypes

Glucagon-like peptide-1 receptor (GLP-1R) agonists decrease body weight and improve glycemic control in obesity and diabetes. Patient compliance and maximal efficacy of GLP-1 therapeutics are limited by side effects including nausea and emesis. In three different species (i.e., mice, rats, and musk shrews), we show that glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling blocks emesis and attenuates illness behaviors elicited by GLP-1R activation, while maintaining reduced food intake, body weight loss, and improved glucose tolerance. The area postrema and nucleus tractus solitarius (AP/NTS) of the hindbrain are required for food intake and body weight suppression by GLP-1R ligands and processing of emetic stimuli. Utilizing single-nuclei RNA-sequencing, we identified the cellular phenotypes of AP/NTS GIPR- and GLP-1R-expressing cells on distinct populations of inhibitory and excitatory neurons, with the greatest expression of GIPR in GABAergic neurons. This work suggests that combinatorial pharmaceutical targeting of GLP-1R and GIPR will increase efficacy in treating obesity and diabetes by reducing nausea and vomiting.

scholarly journals A single day of mixed-macronutrient overfeeding does not elicit compensatory appetite or energy intake responses but exaggerates postprandial lipaemia during the next day in healthy young men

2019 ◽  
Vol 121 (8) ◽  
pp. 945-954 ◽  
Author(s):  
Kevin Deighton ◽  
Andy J. King ◽  
Jamie Matu ◽  
Oliver M. Shannon ◽  
Oliver Whiteman ◽  
...  
Keyword(s):  
Energy Balance ◽  
Energy Intake ◽  
Repeated Measures ◽  
Peptide Yy ◽  
Tolerance Test ◽  
Positive Energy ◽  
Cvd Risk ◽  
Postprandial Lipaemia ◽  
Repeated Measures Design ◽  
Glucagon Like Peptide 1

AbstractDiscrete episodes of overconsumption may induce a positive energy balance and impair metabolic control. However, the effects of an ecologically relevant, single day of balanced macronutrient overfeeding are unknown. Twelve healthy men (of age 22 (sd 2) years, BMI 26·1 (sd 4·2) kg/m2) completed two 28 h, single-blind experimental trials. In a counterbalanced repeated measures design, participants either consumed their calculated daily energy requirements (energy balance trial (EB): 10 755 (sd 593) kJ) or were overfed by 50 % (overfeed trial (OF): 16 132 (sd 889) kJ) under laboratory supervision. Participants returned to the laboratory the next day, after an overnight fast, to complete a mixed-meal tolerance test (MTT). Appetite was not different between trials during day 1 (P>0·211) or during the MTT in the fasted or postprandial state (P>0·507). Accordingly, plasma acylated ghrelin, total glucagon-like peptide-1 and total peptide YY concentrations did not differ between trials during the MTT (all P>0·335). Ad libitum energy intake, assessed upon completion of the MTT, did not differ between trials (EB 6081 (sd 2260) kJ; OF 6182 (sd 1960) kJ; P=0·781). Plasma glucose and insulin concentrations were not different between trials (P>0·715). Fasted NEFA concentrations were lower in OF compared with EB (P=0·005), and TAG concentrations increased to a greater extent on OF than on EB during the MTT (P=0·009). The absence of compensatory changes in appetite-related variables after 1 d of mixed macronutrient overfeeding highlights the limited physiological response to defend against excess energy intake. This supports the concept that repeated discrete episodes of overconsumption may promote weight gain, while elevations in postprandial lipaemia may increase CVD risk.

Circulating Concentrations of Human Peptide YY: Influence of Acute and Chronic Energy Balance Changes

2005 ◽  
Vol 113 (S 1) ◽  
Author(s):  
B Otto ◽  
H Rochlitz ◽  
M Möhlig ◽  
L Burget ◽  
J Kampe ◽  
...  
Keyword(s):  
Energy Balance ◽  
Peptide Yy

Influence of acute and chronic energy balance changes on circulating concentrations of human peptide YY

2005 ◽  
Vol 43 (10) ◽  
Author(s):  
B Otto ◽  
F Lippl ◽  
P Pfluger ◽  
J Spranger ◽  
U Cuntz ◽  
...  
Keyword(s):  
Energy Balance ◽  
Peptide Yy

scholarly journals Epigenetic Modulation of TLR4 Expression by Sulforaphane Increases Anti-Inflammatory Capacity in Porcine Monocyte-Derived Dendritic Cells

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 490
Author(s):  
Xueqi Qu ◽  
Christiane Neuhoff ◽  
Mehmet Ulas Cinar ◽  
Maren Pröll ◽  
Ernst Tholen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dendritic Cells ◽  
Epigenetic Modifications ◽  
Dna Demethylation ◽  
Dependent Manner ◽  
Experimental Conditions ◽  
Hdac Activity ◽  
Protein Levels ◽  
Anti Inflammatory ◽  
Epigenetic Modulation

Inflammation is regulated by epigenetic modifications, including DNA methylation and histone acetylation. Sulforaphane (SFN), a histone deacetylase (HDAC) inhibitor, is also a potent immunomodulatory agent, but its anti-inflammatory functions through epigenetic modifications remain unclear. Therefore, this study aimed to investigate the epigenetic effects of SFN in maintaining the immunomodulatory homeostasis of innate immunity during acute inflammation. For this purpose, SFN-induced epigenetic changes and expression levels of immune-related genes in response to lipopolysaccharide (LPS) stimulation of monocyte-derived dendritic cells (moDCs) were analyzed. These results demonstrated that SFN inhibited HDAC activity and caused histone H3 and H4 acetylation. SFN treatment also induced DNA demethylation in the promoter region of the MHC-SLA1 gene, resulting in the upregulation of Toll-like receptor 4 (TLR4), MHC-SLA1, and inflammatory cytokines’ expression at 6 h of LPS stimulation. Moreover, the protein levels of cytokines in the cell culture supernatants were significantly inhibited by SFN pre-treatment followed by LPS stimulation in a time-dependent manner, suggesting that inhibition of HDAC activity and DNA methylation by SFN may restrict the excessive inflammatory cytokine availability in the extracellular environment. We postulate that SFN may exert a protective and anti-inflammatory function by epigenetically influencing signaling pathways in experimental conditions employing porcine moDCs.

Sign in / Sign up

Export Citation Format

Share Document