Rational Design of Dual Peptides Targeting Ghrelin and Y2 Receptors to Regulate Food Intake and Body Weight

2015 ◽  
Vol 58 (10) ◽  
pp. 4180-4193 ◽  
Author(s):  
Tom-Marten Kilian ◽  
Nora Klöting ◽  
Ralf Bergmann ◽  
Sylvia Els-Heindl ◽  
Stefanie Babilon ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Rational Design ◽  
Regulate Food Intake

scholarly journals Regulation of food intake and body weight by recombinant proghrelin

2009 ◽  
Vol 297 (6) ◽  
pp. E1269-E1275 ◽  
Author(s):  
Weizhen Zhang ◽  
Arundhati Majumder ◽  
Xiaobin Wu ◽  
Michael W. Mulholland
Keyword(s):  
Body Weight ◽  
Amino Acid ◽  
Energy Metabolism ◽  
Food Intake ◽  
Normal Saline ◽  
Biological Function ◽  
Intraperitoneal Administration ◽  
Fat Consumption ◽  
Regulate Food Intake ◽  
Cumulative Food Intake

Ghrelin is a 28-amino-acid hormone derived from the endoproteolytic processing of its prehormone proghrelin. Although ghrelin has been reported to regulate food intake and body weight, it is still unknown whether proghrelin exercises any biological function. Here we show that recombinant proghrelin alters food intake and energy metabolism in mice. After intraperitoneal administration of recombinant proghrelin (100 nmol/kg body wt), cumulative food intake was significantly increased at days 1, 2, and 3 (6 ± 0.3, 13 ± 0.5, and 20 ± 0.8 g vs. 5 ± 0.2, 10 ± 0.2, and 16 ± 0.3 g of the control mice receiving normal saline, respectively, n = 6, P < 0.05). Twelve-hour cumulative food intake in the light photo period in mice treated with proghrelin increased significantly relative to the control (2.1 ± 0.04 vs. 1.3 ± 0.2 g, n = 6, P < 0.05). No change in 12-h cumulative food intake in the dark photo period was observed between mice treated with proghrelin and vehicle (4.2 ± 0.6 vs. 4.3 ± 0.6 g, n = 6, P > 0.05). This is associated with a decrease in body weight (0.42 ± 0.04 g) for mice treated with proghrelin, whereas control animals gained body weight (0.31 ± 0.04 g). Mice treated with proghrelin demonstrate a significant decrease in respiratory quotient, indicating an increase in fat consumption. Recombinant proghrelin is functionally active with effects on food intake and energy metabolism.

scholarly journals Alterations in Phosphorylated CREB Expression in Different Brain Regions following Short- and Long-Term Morphine Exposure: Relationship to Food Intake

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Xiuhai Ren ◽  
Kabirullah Lutfy ◽  
Michael Mangubat ◽  
Monica G. Ferrini ◽  
Martin L. Lee ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Day Treatment ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Brain Regions ◽  
Dorsomedial Nucleus ◽  
Chronic Morphine ◽  
Regulate Food Intake ◽  
Phosphorylated Creb

Background. Activation of the cyclic adenosine monophosphate (cAMP)/phosphorylated CREB (P-CREB) system in different brain regions has been implicated in mediating opioid tolerance and dependence, while alteration of this system in the lateral hypothalamus (LH) has been suggested to have a role in food intake and body weight.Methods. Given that opioids regulate food intake, we measured P-CREB in different brain regions in mice exposed to morphine treatments designed to induce different degrees of tolerance and dependence.Results. We found that a single morphine injection or daily morphine injections for 8 days did not influence P-CREB levels, while the escalating dose of morphine regimen raised P-CREB levels only in the ventral tegmental area (VTA). Chronic morphine pellet implantation for 7 days raised P-CREB levels in the LH, VTA, and dorsomedial nucleus of the hypothalamus (DM) but not in the nucleus accumbens and amygdala. Increased P-CREB levels in LH, VTA, and DM following 7-day treatment with morphine pellets and increased P-CREB levels in the VTA following escalating doses of morphine were associated with decreased food intake and body weight.Conclusion. The morphine regulation of P-CREB may explain some of the physiological sequelae of opioid exposure including altered food intake and body weight.

scholarly journals Identification of hypothalamic neuron-derived neurotrophic factor as a novel factor modulating appetite

2013 ◽  
Vol 304 (12) ◽  
pp. R1085-R1095 ◽  
Author(s):  
Mardi S. Byerly ◽  
Roy D. Swanson ◽  
Nina N. Semsarzadeh ◽  
Patrick S. McCulloh ◽  
Kiwook Kwon ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Mrna Expression ◽  
Neurotrophic Factor ◽  
Large Scale ◽  
Fed State ◽  
Regulatory Circuit ◽  
Hypothalamic Nuclei ◽  
Important Regulator ◽  
Regulate Food Intake

Disruption of finely coordinated neuropeptide signals in the hypothalamus can result in altered food intake and body weight. We identified neuron-derived neurotrophic factor (NENF) as a novel secreted protein through a large-scale screen aimed at identifying novel secreted hypothalamic proteins that regulate food intake. We observed robust Nenf expression in hypothalamic nuclei known to regulate food intake, and its expression was altered under the diet-induced obese (DIO) condition relative to the fed state. Hypothalamic Nenf mRNA was regulated by brain-derived neurotrophic factor (BDNF) signaling, itself an important regulator of appetite. Delivery of purified recombinant BDNF into the lateral cerebral ventricle decreased hypothalamic Nenf expression, while pharmacological inhibition of trkB signaling increased Nenf mRNA expression. Furthermore, recombinant NENF administered via an intracerebroventricular cannula decreased food intake and body weight and increased hypothalamic Pomc and Mc4r mRNA expression. Importantly, the appetite-suppressing effect of NENF was abrogated in obese mice fed a high-fat diet, demonstrating a diet-dependent modulation of NENF function. We propose the existence of a regulatory circuit involving BDNF, NENF, and melanocortin signaling. Our study validates the power of using an integrated experimental and bioinformatic approach to identify novel CNS-derived proteins with appetite-modulating function and reveals NENF as an important central modulator of food intake.

Effects of Cyproterone Acetate on Body Weight and Food Intake

1973 ◽  
Author(s):  
William W. Beatty ◽  
Thomas R. Vilberg ◽  
Paul B. Revland
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Cyproterone Acetate

FoxO1 ablation in hypothalamic pomc neurons reduces food intake and body weight

2007 ◽  
Vol 2 (S 1) ◽  
Author(s):  
L Plum ◽  
M Matsumoto ◽  
D Accili
Keyword(s):  
Body Weight ◽  
Food Intake

Central Histamine, the H3-Receptor and Obesity Therapy

2019 ◽  
Vol 18 (7) ◽  
pp. 516-522
Author(s):  
Néstor F. Díaz ◽  
Héctor Flores-Herrera ◽  
Guadalupe García-López ◽  
Anayansi Molina-Hernández
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Animal Studies ◽  
Energy Homeostasis ◽  
Receptor Activation ◽  
Receptor Ligands ◽  
Histaminergic System ◽  
H3 Receptor ◽  
Weight One ◽  
The Central Nervous System

The brain histaminergic system plays a pivotal role in energy homeostasis, through H1- receptor activation, it increases the hypothalamic release of histamine that decreases food intake and reduces body weight. One way to increase the release of hypothalamic histamine is through the use of antagonist/inverse agonist for the H3-receptor. Histamine H3-receptors are auto-receptors and heteroreceptors located on the presynaptic membranes and cell soma of neurons, where they negatively regulate the synthesis and release of histamine and other neurotransmitters in the central nervous system. Although several compounds acting as H3-receptor antagonist/inverse agonists have been developed, conflicting results have been reported and only one has been tested as anti-obesity in humans. Animal studies revealed the opposite effect in food intake, energy expeditor, and body weight, depending on the drug, spice, and route of administration, among others. The present review will explore the state of art on the effects of H3-receptor ligands on appetite and body-weight, going through the following: a brief overview of the circuit involved in the control of food intake and energy homeostasis, the participation of the histaminergic system in food intake and body weight, and the H3-receptor as a potential therapeutic target for obesity.

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