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.

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<001) that were unrelated to neonatal nutrition or GLP-1R genotype and that were paralleled by a significant increase in weight Z-score (P<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.

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. 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.

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). 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.

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].