RESUMEN
Knowledge of adipogenetic mechanisms is essential to understand and treat conditions affecting organismal metabolism and adipose tissue health. In Drosophila, mature adipose tissue (fat body) exists in larvae and adults. In contrast to the well-known development of the larval fat body from the embryonic mesoderm, adult adipogenesis has remained mysterious. Furthermore, conclusive proof of its physiological significance is lacking. Here, we show that the adult fat body originates from a pool of undifferentiated mesodermal precursors that migrate from the thorax into the abdomen during metamorphosis. Through in vivo imaging, we found that these precursors spread from the ventral midline and cover the inner surface of the abdomen in a process strikingly reminiscent of embryonic mesoderm migration, requiring fibroblast growth factor (FGF) signaling as well. FGF signaling guides migration dorsally and regulates adhesion to the substrate. After spreading is complete, precursor differentiation involves fat accumulation and cell fusion that produces mature binucleate and tetranucleate adipocytes. Finally, we show that flies where adult adipogenesis is impaired by knock down of FGF receptor Heartless or transcription factor Serpent display ectopic fat accumulation in oenocytes and decreased resistance to starvation. Our results reveal that adult adipogenesis occurs de novo during metamorphosis and demonstrate its crucial physiological role.
Asunto(s)
Adipogénesis , Drosophila , Animales , Drosophila/metabolismo , Cuerpo Adiposo/metabolismo , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Tejido Adiposo/metabolismoRESUMEN
Although the specific form of an organ is frequently important for its function, the mechanisms underlying organ shape are largely unknown. In Drosophila, the wings and halteres, homologous appendages of the second and third thoracic segments, respectively, bear different forms: wings are flat, whereas halteres are globular, and yet both characteristic shapes are essential for a normal flight. The Hox gene Ultrabithorax (Ubx) governs the difference between wing and haltere development, but how Ubx function in the appendages prevents or allows flat or globular shapes is unknown. Here, we show that Ubx downregulates Matrix metalloproteinase 1 (Mmp1) expression in the haltere pouch at early pupal stage, which in turn prevents the rapid clearance of Collagen IV compared with the wing disc. This difference is instrumental in determining cell shape changes, expansion of the disc and apposition of dorsal and ventral layers, all of these phenotypic traits being characteristic of wing pouch development. Our results suggest that Ubx regulates organ shape by controlling Mmp1 expression, and the extent and timing of extracellular matrix degradation.
Asunto(s)
Proteínas de Drosophila/biosíntesis , Matriz Extracelular/metabolismo , Proteínas de Homeodominio/biosíntesis , Discos Imaginales/embriología , Metaloproteinasa 1 de la Matriz/metabolismo , Factores de Transcripción/biosíntesis , Alas de Animales/embriología , Animales , Proteínas de Drosophila/genética , Drosophila melanogaster , Matriz Extracelular/genética , Proteínas de Homeodominio/genética , Metaloproteinasa 1 de la Matriz/genética , Factores de Transcripción/genéticaRESUMEN
Cancer was seen for a long time as a strictly cell-autonomous process in which oncogenes and tumor-suppressor mutations drive clonal cell expansions. Research in the past decade, however, paints a more integrative picture of communication and interplay between neighboring cells in tissues. It is increasingly clear as well that tumors, far from being homogenous lumps of cells, consist of different cell types that function together as complex tissue-level communities. The repertoire of interactive cell behaviors and the quantity of cellular players involved call for a social cell biology that investigates these interactions. Research into this social cell biology is critical for understanding development of normal and tumoral tissues. Such complex social cell biology interactions can be parsed in Drosophila. Techniques in Drosophila for analysis of gene function and clonal behavior allow us to generate tumors and dissect their complex interactive biology with cellular resolution. Here, we review recent Drosophila research aimed at understanding tissue-level biology and social cell interactions in tumors, highlighting the principles these studies reveal.
Asunto(s)
Comunicación Celular/genética , Transformación Celular Neoplásica/genética , Drosophila melanogaster/genética , Animales , Animales Modificados Genéticamente , Membrana Basal/fisiología , Adhesión Celular , Muerte Celular , División Celular , Microambiente Celular , Células Clonales/citología , Proteínas de Drosophila/genética , Proteínas de Drosophila/fisiología , Genes de Insecto , Genes Supresores de Tumor , Homeostasis , Humanos , Discos Imaginales/citología , Inmunidad Innata , Mitosis/efectos de la radiación , Mosaicismo , Neoplasias/genética , Neoplasias/patología , Neoplasias Experimentales/genética , Neoplasias Experimentales/inmunología , Células Madre Neoplásicas/citología , Recombinación Genética/efectos de la radiación , Escape del TumorRESUMEN
Human tumours have a large degree of cellular and genetic heterogeneity. Complex cell interactions in the tumour and its microenvironment are thought to have an important role in tumorigenesis and cancer progression. Furthermore, cooperation between oncogenic genetic lesions is required for tumour development; however, it is not known how cell interactions contribute to oncogenic cooperation. The genetic techniques available in the fruitfly Drosophila melanogaster allow analysis of the behaviour of cells with distinct mutations, making this the ideal model organism with which to study cell interactions and oncogenic cooperation. In Drosophila eye-antennal discs, cooperation between the oncogenic protein Ras(V12) (ref. 5) and loss-of-function mutations in the conserved tumour suppressor scribbled (scrib) gives rise to metastatic tumours that display many characteristics observed in human cancers. Here we show that clones of cells bearing different mutations can cooperate to promote tumour growth and invasion in Drosophila. We found that the Ras(V12) and scrib(-) mutations can also cause tumours when they affect different adjacent epithelial cells. We show that this interaction between Ras(V12) and scrib(-) clones involves JNK signalling propagation and JNK-induced upregulation of JAK/STAT-activating cytokines, a compensatory growth mechanism for tissue homeostasis. The development of Ras(V12) tumours can also be triggered by tissue damage, a stress condition that activates JNK signalling. Given the conservation of the pathways examined here, similar cooperative mechanisms could have a role in the development of human cancers.
Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/fisiología , Proteínas de la Membrana/metabolismo , Neoplasias/metabolismo , Transducción de Señal , Proteínas Supresoras de Tumor/metabolismo , Proteínas ras/metabolismo , Animales , Modelos Animales de Enfermedad , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Quinasas Janus/metabolismo , MAP Quinasa Quinasa 4/metabolismo , Neoplasias/patología , Factores de Transcripción STAT/metabolismoRESUMEN
Cellular imbalances of cholesterol and fatty acid metabolism result in pathological processes, including atherosclerosis and metabolic syndrome. Recent work from our group and others has shown that the intronic microRNAs hsa-miR-33a and hsa-miR-33b are located within the sterol regulatory element-binding protein-2 and -1 genes, respectively, and regulate cholesterol homeostasis in concert with their host genes. Here, we show that miR-33a and -b also regulate genes involved in fatty acid metabolism and insulin signaling. miR-33a and -b target key enzymes involved in the regulation of fatty acid oxidation, including carnitine O-octaniltransferase, carnitine palmitoyltransferase 1A, hydroxyacyl-CoA-dehydrogenase, Sirtuin 6 (SIRT6), and AMP kinase subunit-α. Moreover, miR-33a and -b also target the insulin receptor substrate 2, an essential component of the insulin-signaling pathway in the liver. Overexpression of miR-33a and -b reduces both fatty acid oxidation and insulin signaling in hepatic cell lines, whereas inhibition of endogenous miR-33a and -b increases these two metabolic pathways. Together, these data establish that miR-33a and -b regulate pathways controlling three of the risk factors of metabolic syndrome, namely levels of HDL, triglycerides, and insulin signaling, and suggest that inhibitors of miR-33a and -b may be useful in the treatment of this growing health concern.
Asunto(s)
Ácidos Grasos/metabolismo , Insulina/metabolismo , MicroARNs/biosíntesis , Animales , Enfermedades Cardiovasculares/metabolismo , Colesterol/metabolismo , Citoplasma/metabolismo , Drosophila melanogaster/metabolismo , Homeostasis , Humanos , Inmunohistoquímica/métodos , Lípidos/química , Fosforilación , Procesamiento Postranscripcional del ARN , Transducción de SeñalRESUMEN
The eukaryotic p24 family, consisting of α-, ß-, γ- and δ-p24 subfamilies, has long been known to be involved in regulating secretion. Despite increasing interest in these proteins, fundamental questions remain about their role. Here, we systematically investigated Drosophila p24 proteins. We discovered that members of all four p24 subfamilies are required for general secretion and that their localizations between ER exit site (ERES) and Golgi are interdependent in an αâßδâγ sequence. We also found that localization of p24 proteins and ERES determinant Tango1 requires interaction through their respective GOLD and SH3 lumenal domains, with Tango1 loss sending p24 proteins to the plasma membrane and vice versa. Finally, we show that p24 loss expands the COPII zone at ERES and increases the number of ER-Golgi vesicles, supporting a restrictive role of p24 proteins on vesicle budding for efficient transport. Our results reveal Tango1-p24 interplay as central to the generation of a stable ER-Golgi interface.
Asunto(s)
Translocador Nuclear del Receptor de Aril Hidrocarburo , Proteínas de Drosophila , Retículo Endoplásmico , Aparato de Golgi , Proteínas de Transporte de Membrana , Translocador Nuclear del Receptor de Aril Hidrocarburo/metabolismo , Membrana Celular , Drosophila melanogaster , Proteínas de Drosophila/metabolismo , Retículo Endoplásmico/metabolismo , Aparato de Golgi/metabolismo , Dominios Homologos src , Proteínas de Transporte de Membrana/metabolismoRESUMEN
OBJECTIVE: Shift work is associated with circadian rhythm disorder, impaired sleep and behavioural changes, including eating habits, predisposing to obesity and metabolic dysfunctions. It involves a neuro-hormonal dysregulation of appetite towards positive energy balance, including increased ghrelin and decreased leptin, but little is known about other hormones, such as xenin, derived from the upper gut (like ghrelin), and lower gut hormones. Our objective was to compare night workers with day workers in relation to appetite-regulating hormones and other metabolic parameters. DESIGN: Cross-sectional, observational study. PARTICIPANTS: Twenty-four overweight women, divided into night shift workers (n = 12) and day shift workers (n = 12). MEASUREMENTS: BMI, waist circumference, fat mass percentage; diet composition; Pittsburgh Sleep Quality Index; lipids; adipokines; meal tolerance test curves of glucose, insulin, ghrelin, PYY3-36, oxyntomodulin, xenin, GLP-1; insulin sensitivity (Stumvoll index). RESULTS: Night workers, as compared with day workers, had greater body fat mass percentage and tendency to greater waist circumference despite similar BMI; greater energy intake; impaired sleep; lower insulin sensitivity; increased triglycerides and tendency to increased C-reactive protein; similar levels of leptin and other adipokines. Night workers had a blunted post-meal suppression of ghrelin (AUCi(0-60 min) 19·4 ± 139·9 vs -141·9 ± 9·0 ng/ml·60 min, P < 0·01); blunted rise of xenin (AUC(0-180 min) 8690·9 ± 2988·2 vs 28 504·4 ± 20 308·3 pg/ml·180 min, P < 0·01) and similar curves of PYY3-36, oxyntomodulin and GPL-1. CONCLUSION: Compared with day workers within the same BMI range, night workers presented a disrupted control of ghrelin and xenin, associated with behavioural changes in diet and sleep and increased adiposity and related metabolic alterations.
Asunto(s)
Regulación del Apetito/fisiología , Hormonas Gastrointestinales/fisiología , Ghrelina/fisiología , Neurotensina/fisiología , Tolerancia al Trabajo Programado/fisiología , Adiposidad/fisiología , Adulto , Estudios Transversales , Sistema Digestivo/fisiopatología , Ingestión de Energía/fisiología , Femenino , Hormonas Gastrointestinales/sangre , Ghrelina/sangre , Péptido 1 Similar al Glucagón/sangre , Humanos , Resistencia a la Insulina/fisiología , Neurotensina/sangre , Sobrepeso/sangre , Sobrepeso/patología , Sobrepeso/fisiopatología , Oxintomodulina/sangre , Fragmentos de Péptidos/sangre , Péptido YY/sangre , Trastornos del Sueño del Ritmo Circadiano/sangre , Trastornos del Sueño del Ritmo Circadiano/patología , Trastornos del Sueño del Ritmo Circadiano/fisiopatologíaRESUMEN
OBJECTIVE: To investigate the relationship of the neck circumference (NC) with the metabolic syndrome (MetS) and insulin resistance (IR) in a large Brazilian population-based sample, within a wide range of adiposity and glucose tolerance, and to establish cut-off values of the NC for MetS and IR. CONTEXT: The NC correlates with cardiovascular risk factors, IR and components of MetS. Upper-body subcutaneous (sc) fat, as estimated by the NC, is associated with cardiovascular risk factors as much as abdominal fat, which is usually estimated by the waist circumference (WC). There are few epidemiological population-based studies on the clinical significance of the NC to MetS and IR. DESIGN: This is a cross-sectional study. PATIENTS: About 1053 Brazilian adults (18-60 years). MEASUREMENTS: Patients with BMI 18.5-40.0 kg/m(2), with normal glucose tolerance or type 2 diabetes (T2DM), were submitted to anthropometric measurements including waist circumference (WC), NC and BMI. Abdominal visceral fat (VF) was assessed by ultrasound. Insulin sensitivity (IS) was assessed by euglycaemic-hyperinsulinaemic clamp (10% of total sample) and HOMA-IR. Spearman correlations were used to evaluate the association between NC and IR and MetS risk factors. Receiver operating characteristic (ROC) curves were used for gender-specific cut-off values for the prediction of IR and MetS. Binary logistic regression analysis was used to assess the chance of developing IR or MetS according to the enlargement of NC and WC. RESULTS: The sample consisted of 28.6% men, with a mean age of 39.4 (12 years). T2DM diagnosis was present in 306 individuals, of whom 34% were men. NC correlated with WC and BMI in both men and women (P < 0.001). In both genders, NC showed a positive correlation with triglycerides, fasting glucose, fasting insulin and HOMA-IR, and NC had a negative association with high-density lipoprotein (HDL). NC and IS showed a moderate negative correlation. A significant correlation was demonstrated between VF and NC. In the ROC curves, NC presented the largest AUC for IR in women (P < 0.001), while NC presented a large AUC for MetS in both genders. CONCLUSIONS: Neck circumference measurements are an alternative and innovative approach for determining body fat distribution. The NC is positively associated with MetS risk factors, IR and VF, with established cut-off values for the prediction of MetS and IR.
Asunto(s)
Resistencia a la Insulina , Síndrome Metabólico/diagnóstico , Cuello/anatomía & histología , Adiposidad , Adulto , Índice de Masa Corporal , Brasil , Enfermedades Cardiovasculares/etiología , Estudios Transversales , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Humanos , Grasa Intraabdominal/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Factores de Riesgo , Ultrasonografía , Circunferencia de la CinturaRESUMEN
The fusion of epithelial sheets is an essential and conserved morphogenetic event that requires the maintenance of tissue continuity. This is secured by membrane-bound or diffusible signals that instruct the epithelial cells, in a coordinated fashion, to change shapes and adhesive properties and when, how and where to move. Here we show that during Dorsal Closure (DC) in Drosophila, the Jun kinase (JNK) signaling pathway modulates integrins expression and ensures tissue endurance. An excess of JNK activity, as an outcome of a failure in the negative feedback implemented by the dual-specificity phosphatase Puckered (Puc), promotes the loss of integrins [the ß-subunit Myospheroid (Mys)] and amnioserosa detachment. Likewise, integrins signal back to the pathway to regulate the duration and strength of JNK activity. Mys is necessary for the regulation of JNK activity levels and in its absence, puc expression is downregulated and JNK activity increases.
RESUMEN
OBJECTIVE: To compare duodenal-jejunal bypass (DJB) with standard medical care in nonobese patients with type 2 diabetes and evaluate surgically induced endocrine and metabolic changes. METHODS: Eighteen patients submitted to a DJB procedure met the following criteria: overweight, diabetes diagnosis less than 15 years, current insulin treatment, residual ß-cell function, and absence of autoimmunity. Patients who refused surgical treatment received standard medical care (control group). At baseline, 3, 6, and 12 months after surgery, insulin sensitivity and production of glucagon-like peptide-1 and glucose-insulinotropic polypeptide were assessed during a meal tolerance test. Fasting adipocytokines and dipeptidyl-peptidase-4 concentrations were measured. RESULTS: The mean age of the patients was 50 (5) years, time of diagnosis: 9 (2) years, time of insulin usage: 6 (5) months, fasting glucose: 9.9 (2.5) mmol/dL, and HbA1c (glycosylated hemoglobin) level: 8.9% (1.2%). Duodenal-jejunal bypass group showed greater reductions in fasting glucose (22% vs 6% in control group, P < 0.05) and daily insulin requirement (93% vs 15%, P < 0.01). Twelve patients from DJB group stopped using insulin and showed improvements in insulin sensitivity and ß-cell function (P < 0.01), and reductions in glucose-insulinotropic polypeptide levels (P < 0.001), glucagon during the first 30 minutes after meal (P < 0.05), and leptin levels (P < 0.05). Dipeptidyl-peptidase-4 levels increased after surgery (P < 0.01), but glucagon-like peptide-1 levels did not change. CONCLUSIONS: Duodenal-jejunal bypass improved insulin sensitivity and ß-cell function and reduced glucose-insulinotropic polypeptide, leptin, and glucagon production. Hence, DJB resulted in better glycemic control and reduction in insulin requirement but DJB did not result in remission of diabetes.
Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo , Glucemia/metabolismo , Dipeptidil Peptidasa 4/sangre , Duodeno/cirugía , Polipéptido Inhibidor Gástrico/metabolismo , Péptido 1 Similar al Glucagón/sangre , Homeostasis/fisiología , Humanos , Incretinas/metabolismo , Resistencia a la Insulina/fisiología , Yeyuno/cirugía , Persona de Mediana EdadRESUMEN
Development involves tightly paced, reproducible sequences of events, yet it must adjust to conditions external to it, such as resource availability and organismal damage. A major mediator of damage-induced immune responses in vertebrates and insects is JAK/STAT signaling. At the same time, JAK/STAT activation by the Drosophila Upd cytokines is pleiotropically involved in normal development of multiple organs. Whether inflammatory and developmental JAK/STAT roles intersect is unknown. Here, we show that JAK/STAT is active during development of the prothoracic gland (PG), which controls metamorphosis onset through ecdysone production. Reducing JAK/STAT signaling decreased PG size and advanced metamorphosis. Conversely, JAK/STAT hyperactivation by overexpression of pathway components or SUMOylation loss caused PG hypertrophy and metamorphosis delay. Tissue damage and tumors, known to secrete Upd cytokines, also activated JAK/STAT in the PG and delayed metamorphosis, at least in part by inducing expression of the JAK/STAT target Apontic. JAK/STAT damage signaling, therefore, regulates metamorphosis onset by co-opting its developmental role in the PG. Our findings in Drosophila provide insights on how systemic effects of damage and cancer can interfere with hormonally controlled development and developmental transitions.
Asunto(s)
Proteínas de Drosophila , Drosophila , Animales , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Ecdisona/metabolismo , Regulación del Desarrollo de la Expresión Génica , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Surgical treatment of chronic pancreatitis is indicated for intractable pain. Frey's procedure is an accepted treatment for this disease. The aim of the present study was to describe a single-centre experience in the treatment of chronic pancreatitis using Frey's procedure. METHODS: A retrospective analysis of 73 patients who underwent a Frey's procedure between 1991 to 2007 and had at least 1 year of follow-up. Demographics, indication for surgery, peri-operative complications and late outcomes were analysed. RESULTS: The median age was 39.9 years. Seventy out of the 73 (95.8%) patients were male. The median pre-operative body mass index (BMI) was 19.1 kg/m(2). All patients had abdominal pain, 34 (46.6%) of them daily and 13 (17.8%) weekly, with moderate or severe intensity in 98.6% (n= 72). The aetiology was secondary to alcohol in 70 patients (95.9%), with a median consumption of 278 g per day. The surgical morbidity rate was 28.7%; there were no deaths. Median post-operative follow-up was 77.0 months; 64 patients (91.4%) had complete pain relief and post-operative BMI was 22.4 kg/m(2) (P<0.001). All patients with pre-operative endocrine and exocrine insufficiencies showed no reversal of the situation. New onset insufficiencies appeared late. CONCLUSIONS: Frey's procedure was a safe and effective therapeutic option for the surgical treatment of patients with intractable pain caused by chronic pancreatitis.
Asunto(s)
Pancreatectomía/métodos , Pancreatoyeyunostomía , Pancreatitis Crónica/cirugía , Dolor Abdominal/etiología , Dolor Abdominal/cirugía , Adulto , Anciano , Brasil , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Dolor Intratable/etiología , Dolor Intratable/cirugía , Pancreatectomía/efectos adversos , Pancreatoyeyunostomía/efectos adversos , Pancreatitis Crónica/etiología , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Secretory cargos are collected at endoplasmic reticulum (ER) exit sites (ERES) before transport to the Golgi apparatus. Decades of research have provided many details of the molecular events underlying ER-Golgi exchanges. Essential questions, however, remain about the organization of the ER-Golgi interface in cells and the type of membrane structures mediating traffic from ERES. To investigate these, we use transgenic tagging in Drosophila flies, 3D-structured illumination microscopy (SIM), and focused ion beam scanning electron microscopy (FIB-SEM) to characterize ERES-Golgi units in collagen-producing fat body, imaginal discs, and imaginal discs overexpressing ERES determinant Tango1. Facing ERES, we find a pre-cis-Golgi region, equivalent to the vertebrate ER-Golgi intermediate compartment (ERGIC), involved in both anterograde and retrograde transport. This pre-cis-Golgi is continuous with the rest of the Golgi, not a separate compartment or collection of large carriers, for which we find no evidence. We observe, however, many vesicles, as well as pearled tubules connecting ERES and Golgi.
Asunto(s)
Vesículas Cubiertas por Proteínas de Revestimiento/metabolismo , Drosophila/metabolismo , Retículo Endoplásmico/metabolismo , Aparato de Golgi/metabolismo , Factor 1 de Ribosilacion-ADP/metabolismo , Animales , Animales Modificados Genéticamente/genética , Animales Modificados Genéticamente/metabolismo , Translocador Nuclear del Receptor de Aril Hidrocarburo/metabolismo , Transporte Biológico , Proteínas de Drosophila/metabolismo , Retículo Endoplásmico/química , Aparato de Golgi/química , Proteínas de la Matriz de Golgi/metabolismo , Microscopía Electrónica de Rastreo , Proteínas de Unión al GTP Monoméricas/metabolismoRESUMEN
Mechanoreceptor cells develop a specialized cytoskeleton that plays structural and sensory roles at the site of mechanotransduction. However, little is known about how the cytoskeleton is organized and formed. Using electron tomography and live-cell imaging, we resolve the 3D structure and dynamics of the microtubule-based cytoskeleton in fly campaniform mechanosensory cilia. Investigating the formation of the cytoskeleton, we find that katanin p60-like 1 (kat-60L1), a neuronal type of microtubule-severing enzyme, serves two functions. First, it amplifies the mass of microtubules to form the dense microtubule arrays inside the sensory cilia. Second, it generates short microtubules that are required to build the nanoscopic cytoskeleton at the mechanotransduction site. Additional analyses further reveal the functional roles of Patronin and other potential factors in the local regulatory network. In all, our results characterize the specialized cytoskeleton in fly external mechanosensory cilia at near-molecular resolution and provide mechanistic insights into how it is formed.
Asunto(s)
Proteínas de Drosophila/metabolismo , Katanina/metabolismo , Mecanotransducción Celular , Animales , Polaridad Celular , Drosophila melanogaster/metabolismo , Drosophila melanogaster/ultraestructura , Extremidades/fisiología , Microtúbulos/metabolismo , Microtúbulos/ultraestructura , Modelos Biológicos , Orgánulos/metabolismo , Orgánulos/ultraestructura , Receptores de Superficie Celular/metabolismoRESUMEN
BACKGROUND: While evidence of improved renal function following gastric bypass exists, pre-operative predictors of this improvement are not completely known. OBJECTIVES: To assess the glomerular filtration rate (GFR) 1 year after Roux-en-Y gastric bypass (RYGB) and to identify pre-operative predictors associated with the improvement of renal function. METHODS: A historical cohort study, which included 109 obese patients before and 12 months after RYGB, was classified into subgroups according to GFR (normofiltration, hypofiltration (GFR < 5th percentile), and hyperfiltration (GFR > 95th percentile)). The 5th and 95th percentiles were 90 and 120 mL/min/1.73 m2, respectively. The primary outcome was the variation of GFR (%GFR) estimated by the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) formula, calculated using serum creatinine, ethnicity, and gender. RESULTS: The mean age was 38.3 ± 10.3 years and 77% were female; 52.3% presented hypertension and 27.5% type 2 diabetes. One year after surgery, the mean BMI decreased from 36.7 ± 3.6 to 28.8 ± 3.3 kg/m2 (p < 0.001). Pre-surgically, 37.6% presented hypofiltration, 47.7% normofiltration, and 14.7% hyperfiltration. The overall GFR increased from 95.5 ± 19 to 104 ± 16.4 mL/min (10.9%) (p < 0.001). The overall post-surgical %GFR was negatively correlated with the pre-surgical GFR (R = - 0.687; p < 0.001). In the hypofiltration and normofiltration subgroups, the post-surgical %GFR was negatively correlated with age (R = - 0.328, p = 0.036; and R = - 0.355, p = 0.004, respectively) and pre-surgical GFR (R = - 0.436, p = 0.04; and R = - 0.528, p < 0.001, respectively). CONCLUSION: RYGB led to a significant improvement in renal function, mainly among patients with a worse pre-operative renal function. In the hypofiltration and normofiltration subgroups, a younger age was associated with better outcomes.
Asunto(s)
Derivación Gástrica , Tasa de Filtración Glomerular/fisiología , Enfermedades Renales/diagnóstico , Enfermedades Renales/cirugía , Obesidad Mórbida/cirugía , Adulto , Estudios de Cohortes , Femenino , Derivación Gástrica/métodos , Humanos , Enfermedades Renales/complicaciones , Enfermedades Renales/fisiopatología , Masculino , Persona de Mediana Edad , Obesidad Mórbida/complicaciones , Obesidad Mórbida/diagnóstico , Obesidad Mórbida/fisiopatología , Periodo Preoperatorio , Pronóstico , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/fisiopatología , Estudios Retrospectivos , Resultado del Tratamiento , Pérdida de Peso/fisiologíaRESUMEN
BACKGROUND: The relationship between non-alcoholic fatty liver disease (NAFLD) and myocardial function seems to be more than just the effect of mutual metabolic risk factors. OBJECTIVE: To determine whether there is a significant association between NAFLD assessed by means of liver biopsy and left ventricular function expressed by the estimated ejection fraction among individuals with obesity. METHODS: This is a cross-sectional study which enrolled individuals who consecutively underwent bariatric surgery. NAFLD was assessed by means of liver biopsies which were systematically collected during the procedures. The estimated ejection fraction was obtained by means of transthoracic echocardiograms. The main outcome evaluated was a possible association between NAFLD features and ejection fraction. The results of liver biopsies and the respective degrees of severity of each NAFLD feature were also correlated with the ejection fraction and main anthropometric, biochemical, and clinical variables. RESULTS: Of 112 individuals, 86.6% were female and the mean age was 38.5 ± 9.3 years. It was observed that the average estimated ejection fraction (EEF) was significantly lower among individuals with liver fibrosis (67.6 ± 5.5% vs. 70.8 ± 4.9%, p = 0.008). After adjustment for confounding variables in a multivariate model, the degree of liver fibrosis was independently associated with the EEF (R = - 0.3, p = 0.02). CONCLUSION: Among individuals with morbid obesity, the findings of this study are suggestive that liver fibrosis confirmed by histopathological examination is associated with a slight impairment of left ventricular function. Further studies are needed to confirm this association.
Asunto(s)
Cirugía Bariátrica , Cardiopatías/etiología , Cardiopatías/cirugía , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Volumen Sistólico/fisiología , Adulto , Cirugía Bariátrica/métodos , Biopsia , Estudios Transversales , Femenino , Cardiopatías/epidemiología , Cardiopatías/fisiopatología , Humanos , Hígado/patología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/epidemiología , Cirrosis Hepática/fisiopatología , Cirrosis Hepática/cirugía , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Enfermedad del Hígado Graso no Alcohólico/cirugía , Obesidad Mórbida/epidemiología , Obesidad Mórbida/fisiopatología , Factores de RiesgoRESUMEN
Drosophila imaginal discs are monolayered epithelial invaginations that grow during larval stages and evert at metamorphosis to assemble the adult exoskeleton. They consist of columnar cells, forming the imaginal epithelium, as well as squamous cells, which constitute the peripodial epithelium and stalk (PS). Here, we uncover a new morphogenetic/cellular mechanism for disc eversion. We show that imaginal discs evert by apposing their peripodial side to the larval epidermis and through the invasion of the larval epidermis by PS cells, which undergo a pseudo-epithelial-mesenchymal transition (PEMT). As a consequence, the PS/larval bilayer is perforated and the imaginal epithelia protrude, a process reminiscent of other developmental events, such as epithelial perforation in chordates. When eversion is completed, PS cells localize to the leading front, heading disc expansion. We found that the JNK pathway is necessary for PS/larval cells apposition, the PEMT, and the motile activity of leading front cells.
Asunto(s)
Drosophila/embriología , Regulación del Desarrollo de la Expresión Génica , Proteínas Quinasas JNK Activadas por Mitógenos , Quinasas de Proteína Quinasa Activadas por Mitógenos/fisiología , Transducción de Señal , Alas de Animales/embriología , Animales , Tipificación del Cuerpo , División Celular , Línea Celular , Drosophila melanogaster/metabolismo , Embrión no Mamífero/fisiología , Epidermis/embriología , Epidermis/metabolismo , Epitelio/metabolismo , Inmunohistoquímica , MAP Quinasa Quinasa 4 , Mesodermo/metabolismo , Microscopía Fluorescente , Modelos Biológicos , Fenotipo , Factores de TiempoRESUMEN
BACKGROUND: A 24-week interventional prospective trial was performed to compare the benefits of open duodenal-jejunal exclusion surgery (GJB) with a matched control group on standard medical care. METHODS: One-hundred eighty patients were screened for the surgical approach. Twelve patients accepted to be operated and presented the full eligibility criteria for surgery that includes overweight BMI (25-29.9 kg/m2), T2DM diagnosis for less than 15 years, insulin-treated patients, no history of major complications, preserved beta-cell function, and absence of autoimmunity. A matched control group (CG) of patients whom refused surgical treatment was placed to receive standard care. Patients had age of 50 (5) years, time of diagnosis 9 years (range, 3 to 15 years), time of insulin usage 6 months (range, 3 to 48 months), fasting glucose (FG), 9.8 (2.5) mg/dL, and glycated hemoglobin (A1C) 8.90 (2.12)%. RESULTS: At 24 weeks after surgery, patients experienced greater reductions on FG (14% vs. 7% on CG), A1C (from 8.78 to 7.84 in GJB-p<0.01 and 8.93 to 8.71 in CG; p<0.05 between groups) and reductions on average daily insulin requirement (93% vs. 29%, p<0.01). Ten patients stopped insulin usage in GJB but they remain taking oral medications. No differences were observed in both groups regarding BMI, body distribution and composition, blood pressure, and lipids. CONCLUSIONS: In conclusion, duodenal-jejunal exclusion was an effective treatment for nonobese T2DM subjects. GJB was superior to standard care in achieving better glycemic control along with reduction in insulin requirements.
Asunto(s)
Diabetes Mellitus Tipo 2/cirugía , Derivación Gástrica/métodos , Sobrepeso/cirugía , Glucemia/metabolismo , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Duodeno/cirugía , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Yeyuno/cirugía , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estómago/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: It has been proposed that there is improvement in glucose and insulin metabolism after weight loss in patients who underwent diet restriction and bariatric surgery. METHODS: Eleven normal glucose tolerant (NGT) morbidly obese patients [body mass index (BMI), 46.1+/-2.27 g/m2] and eight abnormal glucose metabolism (AGM) obese patients (BMI, 51.20 kg/m2) were submitted to diet-restriction and bariatric surgery. Prospective study on weight loss changes, over the glucose, insulin metabolism, glucagon-like peptide-1 (GLP-1), and adiponectin levels were evaluated by oral glucose tolerance test during three periods: T1 (first evaluation), T2 (pre-surgery), and T3 (9 months after surgery). RESULTS: Insulin levels improved after surgery. T1 was 131.1+/-17.60 pmol/l in the NGT group and 197.57+/-57.94 pmol/l in the AGM group, and T3 was 72.48+/-3.67 pmol/l in the NGT group and 61.2+/-9.33 pmol/l in the AGM group. The major reduction was at the first hour of the glucose load as well as fasting levels. At 9 months after surgery (T3), GLP-1 levels at 30 and 60 min had significantly increased in both groups. It was observed that the AGM group had higher levels of GLP-1 at 30 min (34.06+/-6.18 pmol/l) when compared to the NGT group (22.69+/-4.04 pmol/l). Homeostasis model assessment of insulin resistance from the NGT and AGM groups had a significant reduction at periods T3 in relation to T1 and T2. Adiponectin levels had increased concentration in both groups before and after surgical weight loss. However, it did not have any statistical difference between periods T1 vs. T2. CONCLUSIONS: Weight loss by surgery leads to improvement in the metabolism of carbohydrates in relation to sensitivity to the insulin, contributing to the reduction of type 2 diabetes incidence. This improvement also was expressed by the improvement of the levels of adiponectin and GLP-1.