Просмотр исходного текста страницы Physiological-adaptations-following-RouxenY-gastric-bypass-and-the-identification-of-targets-for-bariatric-mimetic-pharmacotherapy-c

and Medical Sciences, University College Dublin, Ireland. Electronic address: and Medical Sciences, University College Dublin, Ireland; Gastrosurgical Laboratory, University of Gothenburg, Sweden; Investigative Science, Imperial The present opinion article provides an overview of the key improvements in metabolic and cardiovascular health following Roux-en-Y Gastric Bypass (RYGB). Some clinically important long-term complications of RYGB are also briefly described to contextualise the potential value of finding selective non-surgical means of replicating only the beneficial aspects of RYGB. Three biological responses linked to changes in gastrointestinal tract structure and function post-RYGB, that are implicated in the clinical efficacy of RYGB and that have actual or potential applications as non-surgical mimetic based approaches are local increases in undiluted bile in the gut lumen and augmented circulating GLP-1 and IGF-I levels are elevated in late infancy in low birth weight infants, independently of GLP-1 receptor polymorphisms and neonatal nutrition.Metabólicas Asociadas (CIBERDEM), ISCIII, Madrid, Spain.Low birth weight followed by rapid postnatal weight gain is associated with increased risks for obesity and diabetes in adulthood.<br /><br /> Modulation of glucagon-like-peptide 1 (GLP-1) secretion by (epi)genetic mechanisms or nutrition may, in part, influence this risk. Formula-fed infants born small-for-gestational-age (SGA) have higher circulating GLP-1 at age 4 months than breastfed SGA or appropriate-for-gestational-age (AGA) infants. Here we assessed GLP-1 concentrations in healthy AGA (n=149) and SGA (n=107) subjects at age 12 months and their association with endocrine-metabolic and body composition parameters and GLP-1 receptor (GLP-1R) rs6923761 and rs3765467 polymorphisms. At birth, cord GLP-1 concentrations were comparable in AGA and SGA infants. At age 12 months, insulin-like growth factor I (IGF-I) and GLP-1 levels were higher than at birth; SGA infants displayed higher IGF-I and GLP-1 concentrations than AGA infants (both P&lt;001) that were unrelated to neonatal nutrition or GLP-1R genotype and that were paralleled by a significant increase in weight Z-score (P&lt;001 vs AGA). In conclusion, SGA infants have augmented IGF-I and prefeeding GLP-1 concentrations in late infancy. Increased GLP-1 levels may impair hypothalamic and/or peripheral GLP-1R signaling, exert long-term negative effects on the hypothalamic nuclei regulating energy homeostasis and increase the risks for obesity and diabetes.<br /><br />Glucagon-like peptide-1 analog therapy in rare genetic diseases: monogenic obesity, monogenic diabetes, and spinal muscular atrophy.Aviv Sourasky Medical Center, 6 Weizmann St, 64239-06, Tel Aviv, Israel.Sourasky Medical Center, Tel Aviv, Israel.Sourasky Medical Center, Tel Aviv, Israel.Tel Aviv Sourasky Medical Center, 6 Weizmann St, 64239-06, Tel Aviv, Israel. AIM: Implementing genetic analyses have unraveled rare alterations causing early-onset obesity and complications, in whom treatment is challenging. [https://navy-cuckoo-hw67fk.mystrikingly.com/blog/glp-1-can-be-secreted-coming-from-m-tissue-from-the-intestinal-mucosa-as-a semaglutide mechanism of action] aimed to report on the effects of adjuvant off-label therapy with liraglutide, glucagon-like peptide-1 analogue (GLP-1a), in rare genetic diagnoses.<br /><br />METHODS: Case scenarios and review of the literature.RESULTS: Case 1: Nine-year-old boy with early-onset severe obesity and nonalcoholic fatty liver disease (NAFLD) due to a homozygous mutation in the MC4R gene deteriorated under lifestyle change and metformin therapy [at 10 years: body mass index (BMI) 51kg/m2, 226% of the 95th percentile, fat percentage (FP) 65% and muscle-to-fat ratio (MFR) z-score of -21]. One year of liraglutide treatment halted progressive weight gain [BMI 50kg/m2, 212% of the 95th percentile, 63% FP and MFR z-score of -24], with biochemical improvement. Case 2: Twelve-year-old boy with obesity presented with diabetes and progressive NAFLD. Exome analysis revealed two heterozygous mutations compatible with monogenic diabetes (HNF1A) and familial hypercholesterolemia (LDLR). [https://ctxt.io/2/AADwnVdjFw glp-1 receptor agonist] resulted in clinical and laboratory improvement (BMI 87th percentile, 32% FP, MFR z-score of -13, HbA1c 5%) without the expected recovery in liver transaminases. Liraglutide treatment augmented the improvement in weight status (BMI 68th percentile, 22% FP, MFR z-score of -13) with normalization of liver transaminases.<br /><br /> Case 3: Nineteen-year-old male with spinal muscular atrophy type 3 presented with sarcopenic obesity and comorbidities. Treatment strategy included dietary counseling and multiple drug therapies (metformin, anti-hypertensive and statins). Liraglutide therapy led to a gradual recovery of metabolic complications allowing tapering-down other CONCLUSIONS: Considering the pleiotropic effects of GLP1-a beyond BMI reduction, this treatment modality may serve as a game changer in challenging cases.3101. Zhonghua Yi Xue Za Zhi. 2011 May 31;91(20):1413-6.[Effects of glucagon-like peptide-1 on the free fatty acid-induced expression of pancreatic derived factor in cultured β-TC3 cell line].