RESUMO
Xia-Gibbs syndrome (XGS) is a syndromic form of intellectual disability caused by heterozygous AHDC1 variants, but the pathophysiological mechanisms underlying this syndrome are still unclear. In this manuscript, we describe the development of two different functional models: three induced pluripotent stem cell (iPSC) lines with different loss-of-function (LoF) AHDC1 variants, derived by reprogramming peripheral blood mononuclear cells from XGS patients, and a zebrafish strain with a LoF variant in the ortholog gene (ahdc1) obtained through CRISPR/Cas9-mediated editing. The three iPSC lines showed expression of pluripotency factors (SOX2, SSEA-4, OCT3/4, and NANOG). To verify the capacity of iPSC to differentiate into the three germ layers, we obtained embryoid bodies (EBs), induced their differentiation, and confirmed the mRNA expression of ectodermal, mesodermal, and endodermal markers using the TaqMan hPSC Scorecard. The iPSC lines were also approved for the following quality tests: chromosomal microarray analysis (CMA), mycoplasma testing, and short tandem repeat (STR) DNA profiling. The zebrafish model has an insertion of four base pairs in the ahdc1 gene, is fertile, and breeding between heterozygous and wild-type (WT) animals generated offspring in a genotypic proportion in agreement with Mendelian law. The established iPSC and zebrafish lines were deposited on the hpscreg.eu and zfin.org platforms, respectively. These biological models are the first for XGS and will be used in future studies that investigate the pathophysiology of this syndrome, unraveling its underlying molecular mechanisms.
Assuntos
Anormalidades Múltiplas , Células-Tronco Pluripotentes Induzidas , Deficiência Intelectual , Animais , Deficiência Intelectual/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Peixe-Zebra/genética , Leucócitos Mononucleares , Anormalidades Múltiplas/genética , Diferenciação Celular/genética , SíndromeRESUMO
PURPOSE: Bariatric surgery is effective in controlling severe obesity. However, studies investigating the impact of surgically induced weight loss on cardiorespiratory and metabolic responses during maximal effort are controversial. The aim of this study was to assess cardiorespiratory and metabolic responses in women with obesity after bariatric surgery. MATERIALS AND METHODS: We performed a secondary analysis on data from a pilot study with women with obesity submitted to bariatric surgery and who did not participate in a controlled physical training program. Anthropometry, pulmonary function (spirometry), and cardiorespiratory fitness (cardiopulmonary exercise testing [CPX]) were assessed before and after bariatric surgery. RESULTS: Thirty-four women were included (38.7 ± 9.6 years, body mass index = 44.1 ± 6.3 kg/m2). Postoperative assessment was conducted 9.4 ± 2.7 months after surgery. After surgery, we observed a reduction in all anthropometric measurements (mean loss of 28.6 kg, p < 0.001), and improvement in spirometry values (p < 0.001). Relative VO2peak (mL/kg/min) increased slightly (Δ = 1.7; p = 0.06); however, absolute VO2peak (L/min) reduced significantly (Δ = - 0.398; p < 0.001). We also observed an increase of 1.3 min (p < 0.001) in CPX duration, a reduction of 11.3 bpm (p < 0.001) in resting heart rate, and a decrease of systolic (p = 0.02) and diastolic (p < 0.001) blood pressures at peak effort. CONCLUSION: Surgically induced weight loss without exercise training improved cardiac reserve, ventilatory response, blood pressure, and resting heart rate. Cardiorespiratory fitness reflected by relative VO2peak increased slightly, despite increased tolerance to CPX.
Assuntos
Cirurgia Bariátrica , Aptidão Cardiorrespiratória , Obesidade Mórbida , Teste de Esforço/métodos , Feminino , Humanos , Obesidade/cirurgia , Obesidade Mórbida/cirurgia , Consumo de Oxigênio , Projetos Piloto , Redução de PesoRESUMO
BACKGROUND: In severely obese individuals, reducing body weight induced by bariatric surgery is able to promote a reduction in comorbidities and improve respiratory symptoms. However, cardiorespiratory fitness (CRF) reflected by peak oxygen uptake (VO2peak) may not improve in individuals who remain sedentary post-surgery. The objective of this study was to evaluate the effects of a physical training program on CRF and pulmonary function in obese women after bariatric surgery, and to compare them to a control group. METHODS: Twelve obese female candidates for bariatric surgery were evaluated in the preoperative, 3 months postoperative (3MPO), and 6 months postoperative (6MPO) periods through anthropometry, spirometry, and cardiopulmonary exercise testing (CPX). In the 3MPO period, patients were divided into control group (CG, n = 6) and intervention group (IG, n = 6). CG received only general guidelines while IG underwent a structured and supervised physical training program involving aerobic and resistance exercises, lasting 12 weeks. RESULTS: All patients had a significant reduction in anthropometric measurements and an increase in lung function after surgery, with no difference between groups. However, only IG presented a significant increase (p < 0.05) in VO2peak and total CPX duration of 5.9 mL/kg/min (23.8%) and 4.9 min (42.9%), respectively. CONCLUSIONS: Applying a physical training program to a group of obese women after 3 months of bariatric surgery could promote a significant increase in CRF only in the trained group, yet also showing that bariatric surgery alone caused an improvement in the lung function of both groups.