DOCSLIB.ORG

Appetite Control: the Role of the Gastrointestinal Tract

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Appetite Control: the Role of the Gastrointestinal Tract CanCan thethe gutgut fightfight obesity?obesity? TheThe rolerole ofof thethe gastrointestinalgastrointestinal tracttract inin controllingcontrolling whatwhat wewe eateat PhysiologyPhysiology conferenceconference By:By: AmyAmy TiuTiu,, MDMD TheThe problemproblem ofof obesityobesity ResponsibleResponsible forfor aboutabout 300,000300,000 preventablepreventable deathsdeaths perper yearyear inin thethe UnitedUnited StatesStates (second(second onlyonly toto cigarettecigarette asas thethe leadingleading causecause ofof preventablepreventable death)death) Obesity Trends* Among U.S. Adults BRFSS, 1991, 1996, 2003 (*BMI ≥30, or about 30 lbs overweight for 5’4” person) 1991 1996 2003 No Data <10% 10%–14% 15%–19% 20%–24% ? 25% Source: Behavioral Risk Factor Surveillance System, CDC. ObjectivesObjectives UnderstandUnderstand thethe role,role, interactions,interactions, andand clinicalclinical implicationsimplications ofof thethe followingfollowing gutgut peptidespeptides – Ghrelin – PP-fold peptides (PYY,PP, and NPY) – Proglucagon products (OXM and GLP 1) – CCK BrieflyBriefly commentcomment onon thethe effecteffect ofof gastricgastric bypassbypass andand thethe peptidespeptides AppetiteAppetite control:control: BasicBasic StructureStructure CentralCentral andand PeripheralPeripheral NeedsNeeds signalssignals forfor longlong--termterm nutritionalnutritional statusstatus andand acuteacute changeschanges inin nutritionnutrition InvolvesInvolves brainstembrainstem andand rewardreward pathwayspathways BrainBrain receivesreceives signalssignals fromfrom thethe gutgut andand adiposeadipose tissuetissue Figure 1. Interactions among Hormonal and Neural Pathways That Regulate Food Intake and Body-Fat Mass. In this schematic diagram of the brain, the dashed lines indicate hormonal inhibitory effects, and the solid lines stimulatory effects. The paraventricular and arcuate nuclei each contain neurons that are capable of stimulating or inhibiting food intake. Y1R and Y2R denote the Y1 and Y2 subtypes of the neuropeptide Y (NPY) receptor, MC4R melanocortin 4 receptor, PYY peptide YY(3-36)), GHsR growth hormone secretagogue receptor, AgRP agouti-related protein, POMC proopiomelanocortin, (alpha)-MSH (alpha)-melanocyte-stimulating protein, LEPR leptin receptor, and INSR insulin receptor. From: Korner: N Engl J Med, Volume 349(10).September 4, 2003.926-928 CentralCentral Control:Control: TheThe arcuatearcuate nucleusnucleus (ARC)(ARC) WhatWhat isis inin thethe ARC?ARC? NeuropeptideNeuropeptide YY (( ProPro--opiomelanocortinopiomelanocortin NPY)NPY) andand thethe agoutiagouti-- (POMC)(POMC) andand alphaalpha relatedrelated peptidepeptide melanocytemelanocyte-- ((AgRPAgRP)) stimulatingstimulating hormonehormone NPYNPY andand AgRPAgRP areare andand cocainecocaine andand populationspopulations ofof amphetamineamphetamine neuronsneurons thatthat stimulatestimulate regulatedregulated transcripttranscript foodfood intakeintake (CART)(CART) decreasedecrease (orexigenic)(orexigenic) foodfood intakeintake (anorexigenic)(anorexigenic) Wynne et al, Appetite control. J of Endocrinology, 2005. 184, 291-318 PraderPrader--WilliWilli SyndromeSyndrome ChromosomalChromosomal deletiondeletion ofof 15q1115q11--1313 HighHigh ghrelinghrelin levelslevels NoNo cure;cure; treatmenttreatment mainlymainly byby exerciseexercise andand dietdiet controlcontrol GhrelinGhrelin DiscoveredDiscovered inin 19991999 ReleasedReleased inin aa pulsatilepulsatile mannermanner fromfrom thethe oxynticoxyntic cellscells ofof thethe stomach,stomach, alsoalso fromfrom thethe duodenum,duodenum, ileum,ileum, cecum,cecum, andand coloncolon EndogenousEndogenous ligandligand forfor growthgrowth hormonehormone secretagoguesecretagogue receptorreceptor (GHS(GHS--R)R) StimulatesStimulates foodfood intakeintake GhrelinGhrelin UpUp--regulatedregulated byby fastingfasting DecreasedDecreased byby eatingeating ProkineticProkinetic InverseInverse relationshiprelationship withwith BMIBMI Overlaid average plasma ghrelin (•) and leptin ([white circle]) concentrations during a 24-h period in 10 human subjects consuming breakfast (B), lunch (L), and dinner (D) at the times indicated. From: Cummings: Diabetes, Volume 50(8).August 2001.1714-1719 GhrelinGhrelin inin obeseobese subjectssubjects GhrelinGhrelin levelslevels areare lowlow inin obesityobesity DoDo obeseobese subjectssubjects havehave aa normalnormal postpost-- prandialprandial ghrelinghrelin level?level? NO,NO, unlikeunlike leanlean subjects,subjects, obeseobese subjectssubjects dodo notnot havehave thethe samesame rapidrapid postpost--prandialprandial dropdrop inin ghrelinghrelin levelslevels FoodFood failsfails toto decreasedecrease levelslevels inin obeseobese patientspatients GhrelinGhrelin inin obeseobese subjectssubjects afterafter aa mealmeal ObeseObese subjectssubjects dodo notnot exhibitexhibit thethe declinedecline inin ghrelinghrelin afterafter aa mealmeal English et al. Food Fails To SuppressSuppress Ghrelin Levels in Obese Humans. JCEM. 200287(6):2984-2987 Lean subjects Obese subjects GhrelinGhrelin inin anorexiaanorexia andand bulimiabulimia PatientsPatients withwith anorexiaanorexia havehave aa veryvery highhigh level,level, whichwhich returnreturn toto referencereference rangerange afterafter treatmenttreatment andand weightweight gaingain PatientsPatients withwith bulimiabulimia showshow higherhigher circulatingcirculating levelslevels ofof ghrelinghrelin whenwhen comparedcompared withwith controls.controls. FrequentFrequent vomitingvomiting maymay bebe thethe causecause ofof increasedincreased ghrelinghrelin levels.levels. WhatWhat HappensHappens toto GhrelinGhrelin withwith changechange inin bodybody weightweight Ghrelin increased over time in the weight loss group (p<0.05) Ghrelin responds in a compensatory manner to changes in energy homeostasis in healthy young women Leidy et al. Circulating GhreGhrelinlin Is Sensitive to Changes in Body Weight during a Diet and Exercise Program in Normal Weight Young Women. 2004 J Clin Endocrinol Metab 89(6):2659-2664 WhatWhat happenshappens withwith exogenousexogenous infusioninfusion ofof ghrelinghrelin inin humans?humans? IncreasedIncreased appetiteappetite IncreasedIncreased foodfood intakeintake WrenWren etet al.al. showedshowed subjectssubjects consumedconsumed aa meanmean 28%28% additionaladditional caloriescalories fromfrom anan unlimitedunlimited buffetbuffet afterafter administrationadministration LeptinLeptin andand GhrelinGhrelin LeptinLeptin isis anan adipoctyeadipoctye AnalogousAnalogous butbut reciprocalreciprocal toto ghrelinghrelin BothBoth releasedreleased inin pulsatilepulsatile mannermanner CounterCounter regulatoryregulatory rolesroles inin energyenergy homeostasishomeostasis A simplified model of the feeding-regulatory signaling of ghrelin and leptin. Leptin stimulates the POMC anorexigenic pathway and inhibits the NPY–AGRP orexigenic pathway, resulting in reduced food intake. The effect of ghrelin in the hypothalamus is opposite to that of leptin. The orexigenic effect of ghrelin is mediated by activating on the output of the NPY–AGRP neurons. Fasting increases ghrelin and decreases leptin production, leading to the activation of the orexigenic pathway. This response might be important for the adaptation to fasting.Molecular Interventions 2002;2: 495-503 GhrelinGhrelin andand Leptin:Leptin: IsIs therethere anan associationassociation withwith obesity?obesity? ExampleExample Spiegel et al. Sleep Curtailment in Healthy Young Men is Associated with Decreased Leptin levels, Elevated Ghrelin Levels, and Increased Hunger and Appetite. Annals of Internal Medicine 2004;141(11):846-850 Figure 1. Effect of sleep duration on daytime leptin levels, ghrelin levels, hunger, and appetite. A. Mean (±SE) daytime (9:00 a.m. to 9:00 p.m.) profiles of leptin after 2 days with 4 hours in bed or 2 days with 10 hours in bed. Mean leptin levels were 18% lower when sleep was restricted. B. Mean (±SE) daytime (9:00 a.m. to 9:00 p.m.) profiles of ghrelin from 9 of the 12 participants after 2 days with 4 hours in bed or 2 days with 10 hours in bed. Mean ghrelin levels were 28% higher in the afternoon and early evening (12:00 noon to 9:00 p.m.) when sleep was restricted. C and D. Ratings of hunger (C) (0- to 10-cm visual analogue scale) and overall appetite (D) (0- to 70-cm visual analogue scale) after 2 days with 4 hours in bed or 2 days with 10 hours in bed. When sleep was restricted, ratings of hunger and overall appetite increased by 24% and 23%, respectively. ConclusionsConclusions fromfrom StudyStudy LessLess sleep:sleep: decreaseddecreased LeptinLeptin andand increasedincreased GhrelinGhrelin LessLess sleep:sleep: IncreasedIncreased hungerhunger (24%)(24%) andand increaseincrease appetiteappetite (23%)(23%) especiallyespecially forfor caloriecalorie densedense foodsfoods NoNo changechange inin weightweight lossloss oror energyenergy supplysupply FurtherFurther studiesstudies areare neededneeded toto clarifyclarify ifif sleepsleep deprivation,deprivation, leptin,leptin, andand ghrelinghrelin areare associatedassociated withwith obesityobesity GhrelinGhrelin hashas otherother associationsassociations LeptinLeptin maymay notnot bebe thethe onlyonly peptidepeptide associatedassociated withwith GhrelinGhrelin OrexinOrexin fromfrom thethe laterallateral hypothalamushypothalamus maymay alsoalso bebe involvedinvolved inin aa balancebalance withwith ghrelinghrelin.. OfOf note,note, disruptiondisruption ofof thisthis systemsystem isis aa majormajor causecause ofof narcolepsynarcolepsy AlsoAlso associatedassociated
Load more

Recommended publications
  • Methylphenidate Hydrochloride
    Application for Inclusion to the 22nd Expert Committee on the Selection and Use of Essential Medicines: METHYLPHENIDATE HYDROCHLORIDE December 7, 2018 Submitted by: Patricia Moscibrodzki, M.P.H., and Craig L. Katz, M.D. The Icahn School of Medicine at Mount Sinai Graduate Program in Public Health New York NY, United States Contact: [email protected] TABLE OF CONTENTS Page 3 Summary Statement Page 4 Focal Point Person in WHO Page 5 Name of Organizations Consulted Page 6 International Nonproprietary Name Page 7 Formulations Proposed for Inclusion Page 8 International Availability Page 10 Listing Requested Page 11 Public Health Relevance Page 13 Treatment Details Page 19 Comparative Effectiveness Page 29 Comparative Safety Page 41 Comparative Cost and Cost-Effectiveness Page 45 Regulatory Status Page 48 Pharmacoepial Standards Page 49 Text for the WHO Model Formulary Page 52 References Page 61 Appendix – Letters of Support 2 1. Summary Statement of the Proposal for Inclusion of Methylphenidate Methylphenidate (MPH), a central nervous system (CNS) stimulant, of the phenethylamine class, is proposed for inclusion in the WHO Model List of Essential Medications (EML) & the Model List of Essential Medications for Children (EMLc) for treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) under ICD-11, 6C9Z mental, behavioral or neurodevelopmental disorder, disruptive behavior or dissocial disorders. To date, the list of essential medications does not include stimulants, which play a critical role in the treatment of psychotic disorders. Methylphenidate is proposed for inclusion on the complimentary list for both children and adults. This application provides a systematic review of the use, efficacy, safety, availability, and cost-effectiveness of methylphenidate compared with other stimulant (first-line) and non-stimulant (second-line) medications.
    [Show full text]
  • The Impact of a Plant-Based Diet on Gestational Diabetes:A Review
    antioxidants Review The Impact of a Plant-Based Diet on Gestational Diabetes: A Review Antonio Schiattarella 1 , Mauro Lombardo 2 , Maddalena Morlando 1 and Gianluca Rizzo 3,* 1 Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; [email protected] (A.S.); [email protected] (M.M.) 2 Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy; [email protected] 3 Independent Researcher, Via Venezuela 66, 98121 Messina, Italy * Correspondence: [email protected]; Tel.: +39-320-897-6687 Abstract: Gestational diabetes mellitus (GDM) represents a challenging pregnancy complication in which women present a state of glucose intolerance. GDM has been associated with various obstetric complications, such as polyhydramnios, preterm delivery, and increased cesarean delivery rate. Moreover, the fetus could suffer from congenital malformation, macrosomia, neonatal respiratory distress syndrome, and intrauterine death. It has been speculated that inflammatory markers such as tumor necrosis factor-alpha (TNF-α), interleukin (IL) 6, and C-reactive protein (CRP) impact on endothelium dysfunction and insulin resistance and contribute to the pathogenesis of GDM. Nutritional patterns enriched with plant-derived foods, such as a low glycemic or Mediterranean diet, might favorably impact on the incidence of GDM. A high intake of vegetables, fibers, and fruits seems to decrease inflammation by enhancing antioxidant compounds. This aspect contributes to improving insulin efficacy and metabolic control and could provide maternal and neonatal health benefits. Our review aims to deepen the understanding of the impact of a plant-based diet on Citation: Schiattarella, A.; Lombardo, oxidative stress in GDM.
    [Show full text]
  • Associations Between Serum Leptin Level and Bone Turnover in Kidney Transplant Recipients
    Associations between Serum Leptin Level and Bone Turnover in Kidney Transplant Recipients ʈ ʈ ʈ Csaba P. Kovesdy,*† Miklos Z. Molnar,‡§ Maria E. Czira, Anna Rudas, Akos Ujszaszi, Laszlo Rosivall,‡ Miklos Szathmari,¶ Adrian Covic,** Andras Keszei,†† Gabriella Beko,‡‡ ʈ Peter Lakatos,¶ Janos Kosa,¶ and Istvan Mucsi §§ *Division of Nephrology, Salem Veterans Affairs Medical Center, Salem, Virginia; †Division of Nephrology, University of Virginia, Charlottesville, Virginia; ‡Institute of Pathophysiology, Semmelweis University, Budapest, Hungary; §Harold Simmons Center for Chronic Disease Research & Epidemiology, Los Angeles Biomedical Research Institute at ʈ Harbor-University of California–Los Angeles Medical Center, Torrance, California; Institute of Behavioral Sciences, Semmelweis University, Budapest, Hungary; ¶First Department of Internal Medicine, Semmelweis University, Budapest, Hungary; **University of Medicine Gr T Popa, Iasi, Romania; ††Department of Epidemiology, Maastricht University, Maastricht, Netherlands; ‡‡Central Laboratory, Semmelweis University, Budapest, Hungary; and §§Division of Nephrology, Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada Background and objectives: Obesity is associated with increased parathyroid hormone (PTH) in the general population and in patients with chronic kidney disease (CKD). A direct effect of adipose tissue on bone turnover through leptin production has been suggested, but such an association has not been explored in kidney transplant recipients. Design, setting, participants, & measurements: This study examined associations of serum leptin with PTH and with biomarkers of bone turnover (serum beta crosslaps [CTX, a marker of bone resorption] and osteocalcin [OC, a marker of bone formation]) in 978 kidney transplant recipients. Associations were examined in multivariable regression models. Path analyses were used to determine if the association of leptin with bone turnover is independent of PTH.
    [Show full text]
  • PAPER Ghrelin Increases Food Intake in Obese As Well As Lean Subjects
    International Journal of Obesity (2005) 29, 1130–1136 & 2005 Nature Publishing Group All rights reserved 0307-0565/05 $30.00 www.nature.com/ijo PAPER Ghrelin increases food intake in obese as well as lean subjects MR Druce1, AM Wren1, AJ Park1, JE Milton1, M Patterson1, G Frost1, MA Ghatei1, C Small1 and SR Bloom1* 1Department of Metabolic Medicine, Imperial College, London, Hammersmith Hospital Campus, London, UK OBJECTIVE: To investigate whether effects on food intake are seen in obese subjects receiving exogenous administration of ghrelin. DESIGN: Randomised, double-blind, placebo-controlled study of intravenous ghrelin at doses 1 pmol/kg/min and 5 pmol/kg/ min. SUBJECTS: In all, 12 healthy lean subjects (mean body mass index (BMI) 20.570.17 kg/m2) and 12 healthy overweight and obese subjects (mean BMI 31.971.02 kg/m2). MEASUREMENTS: Food intake, appetite and palatability of food, ghrelin and other obesity-related hormones, growth hormone. RESULTS: Low-dose infusion of ghrelin increased ad libitum energy intake at a buffet meal in the obese group only (mean increase 36.679.4%, Po0.01.) High-dose ghrelin infusion increased energy intake in both groups (mean increase 20.1710.6% in the lean and 70.1715.5% in the obese, Po0.01 in both cases.) Ghrelin infusion increased palatability of food in the obese group. CONCLUSION: Ghrelin increases food intake in obese as well as lean subjects. Obese people are sensitive to the appetite- stimulating effects of ghrelin and inhibition of circulating ghrelin may be a useful therapeutic target in the treatment of obesity. International Journal of Obesity (2005) 29, 1130–1136.
    [Show full text]
  • Searching for Novel Peptide Hormones in the Human Genome Olivier Mirabeau
    Searching for novel peptide hormones in the human genome Olivier Mirabeau To cite this version: Olivier Mirabeau. Searching for novel peptide hormones in the human genome. Life Sciences [q-bio]. Université Montpellier II - Sciences et Techniques du Languedoc, 2008. English. tel-00340710 HAL Id: tel-00340710 https://tel.archives-ouvertes.fr/tel-00340710 Submitted on 21 Nov 2008 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITE MONTPELLIER II SCIENCES ET TECHNIQUES DU LANGUEDOC THESE pour obtenir le grade de DOCTEUR DE L'UNIVERSITE MONTPELLIER II Discipline : Biologie Informatique Ecole Doctorale : Sciences chimiques et biologiques pour la santé Formation doctorale : Biologie-Santé Recherche de nouvelles hormones peptidiques codées par le génome humain par Olivier Mirabeau présentée et soutenue publiquement le 30 janvier 2008 JURY M. Hubert Vaudry Rapporteur M. Jean-Philippe Vert Rapporteur Mme Nadia Rosenthal Examinatrice M. Jean Martinez Président M. Olivier Gascuel Directeur M. Cornelius Gross Examinateur Résumé Résumé Cette thèse porte sur la découverte de gènes humains non caractérisés codant pour des précurseurs à hormones peptidiques. Les hormones peptidiques (PH) ont un rôle important dans la plupart des processus physiologiques du corps humain.
    [Show full text]
  • Effects of Dietary Macronutrients on Appetite-Related Hormones in Blood on Body Composition of Lean and Obese Rats
    Animal Industry Report Animal Industry Report AS 652 ASL R2081 2006 Effects of Dietary Macronutrients on Appetite-Related Hormones in Blood on Body Composition of Lean and Obese Rats Michelle Bohan Iowa State University Lloyd L. Anderson Iowa State University Allen H. Trenkle Iowa State University Donald C. Beitz Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/ans_air Part of the Agriculture Commons, and the Animal Sciences Commons Recommended Citation Bohan, Michelle; Anderson, Lloyd L.; Trenkle, Allen H.; and Beitz, Donald C. (2006) "Effects of Dietary Macronutrients on Appetite-Related Hormones in Blood on Body Composition of Lean and Obese Rats ," Animal Industry Report: AS 652, ASL R2081. DOI: https://doi.org/10.31274/ans_air-180814-908 Available at: https://lib.dr.iastate.edu/ans_air/vol652/iss1/22 This Companion Animal is brought to you for free and open access by the Animal Science Research Reports at Iowa State University Digital Repository. It has been accepted for inclusion in Animal Industry Report by an authorized editor of Iowa State University Digital Repository. For more information, please contact [email protected]. Iowa State University Animal Industry Report 2006 Effects of Dietary Macronutrients on Appetite-Related Hormones in Blood on Body Composition of Lean and Obese Rats A.S. Leaflet R2081 ghrelin. Ghrelin is an antagonist of leptin by acting upon the neuropeptide Y/Y1 receptor pathway. Leptin causes Michelle Bohan, graduate student of biochemistry; satiety, whereas ghrelin stimulates nutrient intake. Leptin Lloyd Anderson, distinguished professor of animal science; and ghrelin thereby regulate the action of each other.
    [Show full text]
  • Nutrition Tips for Loss of Appetite
    Nutrition Tips for Loss of Appetite Problems such as pain, nausea, vomiting, diarrhea, or a sore or dry mouth may make eating difficult and cause you to lose interest in eating. Depression, stress, and anxiety may also cause loss of appetite. If your appetite is no longer motivating you to eat, you may need to plan your meals. Eat by the clock rather than by your hunger mechanism. For example, eat because it is 9 am, noon, 3pm, 6pm or whatever is realistic for your daily pattern. Snack between meals. Choose high-calorie puddings, shakes, high-calorie / high protein drink supplements, sandwiches with avocados, nuts, cream soups, cooked cereals & vegetables with added butter / margarine or fruit preserves. Use extra oil in salads or any dish that is cooked. Plan for special circumstances. If you have to miss or delay a meal for a test or therapy, bring a snack of nuts, dried fruit, or cheese and crackers. Ask your dietitian if these foods fit into your medical diet. Plan your daily menu in advance. Make a list of your favorite foods and beverages and prepare a shopping list. Have the food available. You may want to portion out snacks and keep them in the refrigerator in ziplock bags so that they are readily available. Enjoy help in preparing your meals. A friend or relative is often happy to help out by preparing food for you. Some grocery stores have computer-shopping services, or web-van type services that can be of help. You are very important – ask for help when you need it, and ideally before you anticipate that you will need it.
    [Show full text]
  • Chapter 10. the Interplay of Genes, Lifestyle, and Obesity
    CHAPTER 10. The interplay of genes, lifestyle, and obesity Paul W. Franks CHAPTER 10 CHAPTER This chapter reviews the evi- long term [1]. Success in pharmaco- marketed for treatment of diabetes: dence supporting a joint effect of therapeutics for weight loss has also (i) metformin, which reduces hepatic genes and lifestyle factors in obesi- been meagre, and in some instances gluconeogenesis (the production of ty, focusing mainly on evidence from disastrous. A handful of anti-obesity glucose in the liver); (ii) sodium-glu- epidemiological studies and clinical medications have been approved cose linked transporter 2 (SGLT2) trials research. by the European Medicines Agency inhibitors, such as empagliflozin, Obesity is the scourge of most (EMA) and the United States Food which reduce re-uptake of glucose contemporary societies; about 40% and Drug Administration (FDA). One in the kidneys and are diuretic; and of adults worldwide are overweight of the most successful of these is (iii) glucagon-like peptide-1 (GLP-1) and 13% are obese (http://www.who. the lipase inhibitor orlistat. Howev- agonists, such as exenatide, which int/mediacentre/factsheets/fs311/ er, because orlistat diminishes in- diminish appetite by delaying gastric en/). Much of the burden that obesity testinal fat absorption, a frequent emptying. However, because all of conveys arises from the life-threat- side-effect of the drug is fatty stool, these drugs can cause side-effects ening diseases it causes, although which many patients cannot toler- and they are not all reimbursable by there are also direct consequences, ate. Other weight-loss drugs, such health insurance providers for treat- because quality of life is often dimin- as rimonabant, are approved for use ment of obesity, they are rarely used ished in people with morbid obesity in the European Union but are not primarily for weight reduction.
    [Show full text]
  • Low Ambient Temperature Lowers Cholecystokinin and Leptin Plasma Concentrations in Adult Men Monika Pizon, Przemyslaw J
    The Open Nutrition Journal, 2009, 3, 5-7 5 Open Access Low Ambient Temperature Lowers Cholecystokinin and Leptin Plasma Concentrations in Adult Men Monika Pizon, Przemyslaw J. Tomasik*, Krystyna Sztefko and Zdzislaw Szafran Department of Clinical Biochemistry, University Children`s Hospital, Krakow, Poland Abstract: Background: It is known that the low ambient temperature causes a considerable increase of appetite. The mechanisms underlying the changes of the amounts of the ingested food in relation to the environmental temperature has not been elucidated. The aim of this study was to investigate the effect of the short exposure to low ambient temperature on the plasma concentration of leptin and cholecystokinin. Methods: Sixteen healthy men, mean age 24.6 ± 3.5 years, BMI 22.3 ± 2.3 kg/m2, participated in the study. The concen- trations of plasma CCK and leptin were determined twice – before and after the 30 min. exposure to + 4 °C by using RIA kits. Results: The mean value of CCK concentration before the exposure to low ambient temperature was 1.1 pmol/l, and after the exposure 0.6 pmol/l (p<0.0005 in the paired t-test). The mean values of leptin before exposure (4.7 ± 1.54 μg/l) were also significantly lower than after the exposure (6.4 ± 1.7 μg/l; p<0.0005 in the paired t-test). However no significant cor- relation was found between CCK and leptin concentrations, both before and after exposure to low temperature. Conclusions: It has been known that a fall in the concentration of CCK elicits hunger and causes an increase in feeding activity.
    [Show full text]
  • Leptin Replacement Reestablishes Brain Insulin Action in The
    Diabetes Care 1 Sabine Frank-Podlech,1–3 Leptin Replacement Reestablishes Julia von Schnurbein,4 Ralf Veit,1–3 Martin Heni,2,3 Jurgen¨ Machann,2,5 Brain Insulin Action in the Jaana M. Heinze,2,3 Stephanie Kullmann,2,3 Jaida Manzoor,6 Hypothalamus in Congenital Saqib Mahmood,7 Hans-Ulrich Haring,¨ 2,3 fi Hubert Preissl,2,3,8,9 Martin Wabitsch,4 Leptin De ciency and Andreas Fritsche2,3 https://doi.org/10.2337/dc17-1867 OBJECTIVE Human obesity is associated with impaired central insulin signaling, and in very rare cases, severe obesity can be caused by congenital leptin deficiency. In such patients, leptin replacement results in substantial weight loss and improvement in peripheral 1 metabolism. Institute for Medical Psychology and Behaviou- ral Neurobiology, University of Tubingen,¨ Tubingen,¨ Germany RESEARCH DESIGN AND METHODS 2 Institute for Diabetes Research and Metabolic In a leptin-deficient patient, we investigated the impact of leptin substitution on Diseases of the Helmholtz Center Munich at the central insulin action, as quantified by changes in neuronal activity after intranasal University of Tubingen,¨ German Center for Dia- insulin application. This was assessed before and during the 1st year of metreleptin betes Research, Tubingen,¨ Germany 3Department of Internal Medicine IV, University substitution. Hospital, Tubingen,¨ Germany 4Division of Pediatric Endocrinology and Diabe- RESULTS tes, Department of Pediatrics and Adolescent After only 1 year, treatment with metreleptin reestablishes brain insulin sensitivity, Medicine, University of Ulm, Ulm, Germany 5 particularly in the hypothalamus and, to a lesser degree, in the prefrontal cortex. Section on Experimental Radiology, Depart- ment of Diagnostic and Interventional Radiol- Results are depicted in comparison with a control group.
    [Show full text]
  • Metabolic Regulation of Fertility Through Presynaptic and Postsynaptic Signaling to Gonadotropin-Releasing Hormone Neurons
    8578 • The Journal of Neuroscience, September 17, 2003 • 23(24):8578–8585 Behavioral/Systems/Cognitive Metabolic Regulation of Fertility through Presynaptic and Postsynaptic Signaling to Gonadotropin-Releasing Hormone Neurons Shannon D. Sullivan, R. Anthony DeFazio, and Suzanne M. Moenter 1Internal Medicine and Cell Biology, University of Virginia, Charlottesville, Virginia 22908 Gonadotropin-releasing hormone (GnRH) neurons form the final common pathway for the central regulation of reproduction and are inhibited by negative energy balance. In normal adults, these neurons maintain elevated intracellular chloride so that GABAA receptor activation is excitatory. We hypothesized that fasting alters homeostatic mechanisms to eliminate excitatory responses to GABA but rejected this hypothesis when brief, local GABA application elicited action currents in GnRH neurons from fed and fasted mice. This response was specific to GABAA receptors, because glycine elicited no response. We next found that fasting reduced the frequency of spontaneous GABAergic postsynaptic currents (PSCs) and that this was reversed by in vivo treatment with leptin during the fast. In the presence of tetrodotoxin to minimize presynaptic actions, leptin also potentiated the postsynaptic response of these cells to GABAA receptor activation. Postsynaptic effects of leptin on GABAergic miniature PSCs were eliminated by inhibiting JAK2/3 (Janus kinase), the tyrosine kinase through which leptin receptors signal. In all experiments, elimination of PSCs at ECl or by treatment with the GABAA receptor antagonist bicuculline confirmed that PSCs were specifically mediated by GABAA receptor chloride channels. These data dem- onstrate that fasting and leptin act presynaptically and postsynaptically to alter GABAergic drive to GnRH neurons, providing evidence for GABAergic communication of metabolic cues to GnRH neurons, and suggest the possibility for functional leptin receptors on GnRH neurons.
    [Show full text]
  • Glucagon-Like Peptide 1 Secretion by the L-Cell the View from Within Gareth E
    Glucagon-Like Peptide 1 Secretion by the L-Cell The View From Within Gareth E. Lim1 and Patricia L. Brubaker1,2 Glucagon-like peptide 1 (GLP-1) is a gut-derived peptide GLP-1 receptor antagonists as well as GLP-1 receptor null secreted from intestinal L-cells after a meal. GLP-1 has mice have demonstrated that GLP-1 makes an essential numerous physiological actions, including potentiation of contribution to the “incretin” effect after a meal (3,4). glucose-stimulated insulin secretion, enhancement of However, GLP-1 secretion is reduced in patients with type ␤-cell growth and survival, and inhibition of glucagon 2 diabetes (5–7), and this may contribute in part to the release, gastric emptying, and food intake. These antidia- reduced incretin effect and the hyperglycemia that is betic effects of GLP-1 have led to intense interest in the use observed in these individuals (8). Thus, interest has now of this peptide for the treatment of patients with type 2 focused on the factors that regulate the release of this diabetes. Oral nutrients such as glucose and fat are potent physiological regulators of GLP-1 secretion, but non-nutri- peptide after nutrient ingestion. Many different GLP-1 ent stimulators of GLP-1 release have also been identified, secretagogues have been described in the literature over including the neuromodulators acetylcholine and gastrin- the past few decades, including nutrients, neurotransmit- releasing peptide. Peripheral hormones that participate in ters, neuropeptides, and peripheral hormones (rev. in energy homeostasis, such as leptin, have also been impli- 9,10). However, the specific receptors, ion channels, and cated in the regulation of GLP-1 release.
    [Show full text]