Control of Food Intake by Gastrointestinal Peptides: Mechanisms of Action and Possible Modulation in the Treatment of Obesity

Prinz, Philip; Stengel, Andreas

doi:10.5056/jnm16194

Cited by 63 publications

(43 citation statements)

References 216 publications

(221 reference statements)

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“…Several gastrointestinal peptides such as cholecystokinin, peptide tyrosine-tyrosine, and nesfatin-1 including GLP-1 have been implicated in the regulation of hunger and satiety. 59 Furthermore, continuous subcutaneous infusion of GLP-1 for 6 weeks into T2DM patients resulted in a reduction in body weight and appetite, in addition to the inhibition of gastric emptying. 60 Thus, GLP-1 peptide has a strong influence on appetite and weight maintenance due to its proposed actions on the gastrointestinal track involving reduction in gastric emptying and gut motility.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Lentivirus-Mediated Glucagon-Like Peptide-1 Gene Therapy for Diabetes

et al. 2018

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Postprandial glucose-induced insulin secretion from the islets of Langerhans is facilitated by glucagon-like peptide-1 (GLP-1)-a metabolic hormone with insulinotropic properties. Among the variety of effects it mediates, GLP-1 induces delta cell secretion of somatostatin, inhibits alpha cell release of glucagon, reduces gastric emptying, and slows food intake. These events collectively contribute to weight loss over time. During type 2 diabetes (T2DM), however, the incretin response to glucose is reduced and accompanied by a moderate reduction in GLP-1 secretion. To compensate for the reduced incretin effect, a human immunodeficiency virus-based lentiviral vector was generated to deliver DNA encoding human GLP-1 (LentiGLP-1), and the anti-diabetic efficacy of LentiGLP-1 was tested in a high-fat diet/streptozotocin-induced model of T2DM. Therapeutic administration of LentiGLP-1 reduced blood glucose levels in obese diabetic Sprague Dawley rats, along with improving insulin sensitivity and glucose tolerance. Normoglycemia was correlated with increased blood GLP-1 and pancreatic beta cell regeneration in LentiGLP-1-treated rats. Plasma triglyceride levels were also normalized after LentiGLP-1 injection. Collectively, these data suggest the clinical potential of GLP-1 gene transfer therapy for the treatment of T2DM.

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Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Lentivirus-Mediated Glucagon-Like Peptide-1 Gene Therapy for Diabetes

et al. 2018

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“…This signaling is mediated by peptide hormones that are released both in the gastrointestinal tract and in the CNS (Wilson & Enriori 2015, Zanchi et al 2017. Anorexigenic hormones involved in short-term regulation include the gut hormones GLP-1, peptide tyrosine tyrosine (PYY), cholecystokinin (CCK), amylin, oxyntomodulin that are controlled by the long-term satiety signal leptin (Frago & Chowen 2015, Prinz & Stengel 2017. These gut hormones are released into the digestive system and then act centrally as satiety signals that decrease food intake; their action occurs specifically in the hypothalamus and brainstem, which act as control centers for hunger and satiety.…”

Section: The Effect Of Anorexigenic Peptides In Ad-like Pathologymentioning

confidence: 99%

“…These peptides are released not only in various parts of the central nervous system (CNS), mainly in the hypothalamus and brainstem (such as anorexigenic cocaine-and amphetamine-regulated transcript peptide, melanocortins or prolactin-releasing peptide and orexigenic neuropeptide Y or orexins), but also in the periphery (such as anorexigenic leptin, glucagon-like peptide and cholecystokinin and orexigenic ghrelin) (Fig. 1), and they all act centrally to regulate energy homeostasis (Spiegelman & Flier 2001, Frago & Chowen 2015, Prinz & Stengel 2017. Although many of these peptides have been known for a relatively long time, their mechanism of action and their interactions are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

The impact of anorexigenic peptides in experimental models of Alzheimer’s disease pathology

Maletı́nská

Popelová

Železná

et al. 2019

Journal of Endocrinology

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Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder in the elderly population. Numerous epidemiological and experimental studies have demonstrated that patients who suffer from obesity or type 2 diabetes mellitus have a higher risk of cognitive dysfunction and AD. Several recent studies demonstrated that food intake-lowering (anorexigenic) peptides have the potential to improve metabolic disorders and that they may also potentially be useful in the treatment of neurodegenerative diseases. In this review, the neuroprotective effects of anorexigenic peptides of both peripheral and central origins are discussed. Moreover, the role of leptin as a key modulator of energy homeostasis is discussed in relation to its interaction with anorexigenic peptides and their analogs in AD-like pathology. Although there is no perfect experimental model of human AD pathology, animal studies have already proven that anorexigenic peptides exhibit neuroprotective properties. This phenomenon is extremely important for the potential development of new drugs in view of the aging of the human population and of the significantly increasing incidence of AD.

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“…Dva su osnovna i međusobno povezana puta kojima se navedena kontrola ostvaruje, djelovanjem na arkvatnu jezgru hipotalamusa te posrednim vagalnim djelovanjem na jezgru solitarnog Procjenjuje se da će 2030. godine oko 38 % svjetske populacije biti preuhranjeno, a oko 20 % pretilo. trakta moždanog debla 8 . Određeni gastrointestinalni peptidi sintetiziraju se i u samom mozgu, gdje djeluju kao neurotransmiteri i/ili neuromodulatori 8 .…”

Section: Uvodunclassified

The role of gastrointestinal peptides in the pathogenesis and treatment of obesity

Poropat

Jurišić‐Eržen

2019

Med flum

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Sažetak. Pretilost predstavlja jedan od najvećih zdravstveno-ekonomskih i socijalnih problema današnjice te se sve veća učestalost pretilosti povezuje s porastom incidencije i pobola niza drugih bolesti, prije svega šećerne bolesti, kardiovaskularnih i cerebrovaskularnih oboljenja te malignih bolesti. U održavanju ravnoteže unosa i potrošnje energije najvažniju regulatornu ulogu ima središnji živčani sustav, odnosno osovina mozak-crijevo, koja se temelji na funkciji niza gastrointestinalnih peptidnih hormona. Djelovanje navedenih peptida izrazito je raznoliko i ovisi o nizu čimbenika, posebno vrsti i količini hrane, energetskom stanju organizma te pratećim bolestima i metaboličkim poremećajima. Djelovanje ovih hormona usko je povezano s endokrinom funkcijom gušterače, lučenjem inzulina i regulacijom glikemije, što ujedno ukazuje i na jasnu povezanost pretilosti i šećerne bolesti. Velik napredak na području razvoja i primjene novih antidijabetika u klasi peptidnih hormona, odnosno inkretina, te utvrđivanje njihovih dodatnih svojstava u smislu redukcije tjelesne težine, otvorili su tijekom posljednjih godina čitavo novo područje istraživanja farmakoterapije pretilosti. Obećavajuće rezultate prije svega pružaju nove mogućnosti kombinacije više lijekova, čime se ponovno stvara mogućnost razvoja adekvatne farmakoterapije kao alternative kirurškom pristupu liječenju pretilosti.Abstract. Obesity is one of the biggest health-economic and social problems of today and its increasing incidence is aassociated with an increasing incidence and morbiditiy of a number of other diseases, primarily diabetes, cardiovascular and cerebrovascular diseases, and malignant diseases as well. The central nervous system, that is the brain-gut axis has the central role in maintaining the balance of input and energy consumption, which is regulated by a variety of gastrointestinal peptide hormones. The role and action of these peptides is highly variable and depends on a number of factors, especially the type and the amount of food, energy status of the organism, and the accompanying diseases and metabolic disorders. They are closely connected with the pancreatic endocrine function, insuline secretion and regulation of glycaemia, which also shows a clear link between obesity and diabetes. A great progress in the development and appication of new antidiabetics in the class of peptide hormones or incretins, and their additional weight-loss properties have opened a whole new field of the pharmacotherapy researches in the treatment of obesity. The promising results are provided by the new drug combinations, which leads to new possibilities of pharmacotherapy as an alternative to the surgical treatment of obesity.

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Control of Food Intake by Gastrointestinal Peptides: Mechanisms of Action and Possible Modulation in the Treatment of Obesity

Cited by 63 publications

References 216 publications

Therapeutic Potential of Lentivirus-Mediated Glucagon-Like Peptide-1 Gene Therapy for Diabetes

Therapeutic Potential of Lentivirus-Mediated Glucagon-Like Peptide-1 Gene Therapy for Diabetes

The impact of anorexigenic peptides in experimental models of Alzheimer’s disease pathology

The role of gastrointestinal peptides in the pathogenesis and treatment of obesity

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