RESUMEN
ETV5 has been described to be involved in the epithelial to mesenchymal transition (EMT) mainly in cancer. It is known that EMT provokes cytoskeleton remodeling, improving cellular migratory, and invasive capabilities. Moreover, overexpression of ETV5 has been correlated to cancer development and this gene has been implicated in cell proliferation. However, little is known about the downregulation of ETV5 expression in a pancreatic cell line and the inverse mesenchymal to epithelial transition (MET). Therefore, we studied the implications of ETV5 silencing over the phenotype of the insulinoma INS-1 (832/13) cell line and described the MET by partial ETV5 silencing in the INS-1 (832/13) cell line. The downregulation of ETV5 expression was obtained by using ETV5 siRNA in the insulinoma rat cell line, INS-1 (832/13). Then, ETV5 knockdown provoked a MET phenotype observed by crystal violet staining and verified by immunohistochemistry against E-cadherin. Wound healing assay showed no migration, and F-actin stain revealed rearrangement of actin microfilaments. In addition, TGFß1 and TGFß3 were downregulated in the absence of ETV5. ETV5 silencing induces epithelial phenotype by downregulating TGFß1 and TGFß3 in INS-1 (832/13) cell line.
Asunto(s)
Insulinoma , Neoplasias Pancreáticas , Humanos , Transición Epitelial-Mesenquimal/genética , Línea Celular Tumoral , Proliferación Celular/genética , Movimiento Celular/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Milk and dairy products are known to have a significant role in human development and tissue maintenance due to their high nutritional value. With the higher incidence of obesity and metabolic diseases, nutrition and public health authorities have recommended the intake of fat-free or low-fat dairy due to the saturated fatty acid content of whole-fat products and their effect on serum cholesterol levels. However, recent studies have questioned the association between milk fat consumption and cardiometabolic risk. This literature review aims to compile the scientific evidence of the metabolic effects of milk fatty acids in clinical and basic research studies, as well as their relationship with metabolic disorders and gut microbiota composition. Research shows that various milk fatty acids exert effects on metabolic alterations (obesity, type 2 diabetes and cardiovascular diseases) by modifying glucose homeostasis, inflammation and lipid profile-related factors. Additionally, recent studies have associated the consumption of milk fatty acids with the production of metabolites and the promotion of healthy gut microbiota. From mainly observational studies, evidence suggests that milk and dairy fatty acids are not directly linked to cardiometabolic risk, but further controlled research is necessary to clarify such findings and to assess whether dietary recommendations to choose low-fat dairy foods are necessary for the population for the prevention of obesity and cardiometabolic disease.
Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Enfermedades Metabólicas , Humanos , Animales , Leche , Ácidos Grasos , Diabetes Mellitus Tipo 2/complicaciones , Grasas de la Dieta/efectos adversos , Obesidad/epidemiología , Dieta con Restricción de Grasas , Enfermedades Metabólicas/epidemiología , Enfermedades Cardiovasculares/epidemiologíaRESUMEN
The transcription factor E-twenty-six variant 5 (ETV5) regulates acute insulin secretion. Adequate insulin secretion is dependent on pancreatic ß-cell size and cell proliferation, but the effects of ETV5 on proliferation, cell number, and viability, as well as its relationship with insulin secretion, have not been established yet. Here, we partially silenced ETV5 in the INS-1 (832/13) cell line by siRNA transfection and then measured secreted insulin concentration at different time points, observing similar levels to control cells. After 72 h of ETV5 silencing, we observed decreased cell number and proliferation, without any change in viability or apoptosis. Thus, partial silencing of ETV5 modulates cell proliferation in INS-1 (832/13) independently of secreted insulin levels via upregulation of E2F1 and of inhibitors of the cyclin/CDKs complexes (p21Cdkn1a , p27Cdkn1b , and p57Cdkn1c ) and downregulation of cell cycle activators (PAK3 and FOS).
Asunto(s)
Genes cdc , Insulina , Animales , Ratas , División Celular , Línea Celular , Proliferación Celular/genética , Insulina/genética , Insulina/metabolismoRESUMEN
BACKGROUND: Obesity is defined as abnormal or excessive fat accumulation, provoking many different diseases, such as obesity and type 2 diabetes. Type 2 diabetes is a chronic-degenerative disease characterized by increased blood glucose levels. Obesity and type 2 diabetes are currently considered public health problems, and their prevalence has increased over the last few years. Because of the high cost involved in the treatment of both diseases, different alternatives have been sought. However, the general population uses medicinal plants, in the form of tea or infusions, to treat different diseases. Therefore, traditional medicine using medicinal plants has been investigated as a possible treatment for type 2 diabetes and body weight control. AIM OF THE STUDY: The purpose of this review is to find medicinal plants used in Mexico that could exert their beneficial effect by regulating insulin secretion and body weight control. MATERIAL AND METHOD: For the development of this review, Mexican plants used in traditional medicine to treat type 2 diabetes and body weight control were searched in PubMed, Google Scholar, and Scopus. The inclusion criteria include plants that presented a significant reduction in blood glucose levels and/or an increase in insulin secretion. RESULTS: We found 306 Mexican plants with hypoglycemic effects. However, plants that did not show evidence of an increase in insulin secretion were eliminated. Finally, only five plants were included in this review: Momordica charantia L. (melón amargo), Cucurbita ficifolia bouché (chilacayote), Coriandrum sativum L. (cilantro), Persea americana Mill. (aguacate) Bidens pilosa (amor seco), including 39 articles in total. Here, we summarized the plant extracts (aqueous and organic) that have previously been reported to present hypoglycemic effects, body weight control, increased secretion and sensitivity of insulin, improvement of pancreatic ß cells, and glucose tolerance. Additionally, these effects may be due to different bioactive compounds present in the plants' extracts. CONCLUSION: Both in vivo and in vitro studies are required to understand the mechanism of action of these plant extracts regarding insulin secretion to be used as a possible treatment for type 2 diabetes and body weight control in the future.
Asunto(s)
Coriandrum , Cucurbita , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucemia , México , Peso Corporal , Obesidad/tratamiento farmacológico , Homeostasis , HipoglucemiantesRESUMEN
BACKGROUND: Metabolic disorders such as obesity and type 2 diabetes (T2D) coincide with an increased expression of pro-inflammatory factors. The NLRP3 inflammasome is a complex that activates the pro-inflammatory cytokine IL-1ß. (NOD-like receptor protein 3). Some nutrients, such as fatty acids, influence inflammatory processes. For example, in clinical studies, higher trans-palmitoyl acid (TP) concentrations coincide with lower adiposity and lower risk of developing T2D. This study aims to evaluate the effect of TP on NLRP3 expression in a rodent model of diet-induced obesity (DIO). METHODS: C57BL/6J mice were fed ad libitum with a control or a high-fat diet (HFD), added with or without TP (3 g/kg diet), for 11 weeks. IL-1ß was quantified in serum, and NLRP3-related gene expression was explored in epididymal adipose tissue. RESULTS: Despite increased weight gain in both high-fat groups, the high-fat TP group gained less weight than the high-fat group. In addition, NLRP3 and caspase-1 expression was higher in the HFD groups, but no differences were observed between the HFD and the HFD TP groups. Serum IL-1ß levels were not different among groups. CONCLUSIONS: Diet supplementation with TP prevents weight gain and has a neutral influence over NLRP3 expression and IL-1ß concentration in a DIO mice model.
INTRODUCCIÓN: Las alteraciones metabólicas como la obesidad y diabetes tipo 2 (DT2) coinciden con la expresión aumentada de factores proinflamatorios. Un complejo que induce la activación de la citocina proinflamatoria IL-1ß es el inflamasoma NLRP3 (NOD-like receptor protein 3). Algunos nutrimentos, como los ácidos grasos, influencian los procesos inflamatorios. Por ejemplo, en estudios clínicos, mayores concentraciones del ácido trans-palmitoléico (TP) coinciden con una menor adiposidad y un menor riesgo de desarrollar DT2. El objetivo de este estudio fue evaluar el efecto del TP sobre la expresión del inflamasoma NLRP3 en un modelo de obesidad inducida por dieta (OID) en roedores. MÉTODOS: Se alimentaron ratones C57BL/6J ad libitum con una dieta control o alta en lípidos (AL), adicionada o no con TP (3 g/kg dieta), durante 11 semanas. Se cuantificó la concentración de IL-1ß en elsuero de los animales, y en el tejido adiposo epididimal se midió la expresión de los componentes del inflamasoma. RESULTADOS: A pesar del aumento de peso en ambos grupos de dieta con alto contenido en lípidos, el grupo alto en lípidos TP ganó menos peso que el grupo AL. Por otro lado, la expresión de genes del inflamasoma resultó mayor en los grupos AL, pero no se encontraron diferencias entre los grupos AL y AL TP. Además, no se observaron diferencias en la concentración de IL-1ß en suero entre grupos. CONCLUSIONES: La dieta suplementada con TP previno el aumento del peso corporal, pero no modificó la expresión de los componentes del inflamasoma ni la concentración de IL-1ß en suero.
Asunto(s)
Diabetes Mellitus Tipo 2 , Inflamasomas , Ratones , Animales , Humanos , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Roedores/metabolismo , Ratones Endogámicos C57BL , Obesidad/etiología , Dieta Alta en Grasa/efectos adversos , Aumento de PesoRESUMEN
Abstract Background: Metabolic disorders such as obesity and type 2 diabetes (T2D) coincide with an increased expression of pro-inflammatory factors. The NLRP3 inflammasome is a complex that activates the pro-inflammatory cytokine IL-1β. (NOD-like receptor protein 3). Some nutrients, such as fatty acids, influence inflammatory processes. For example, in clinical studies, higher trans-palmitoyl acid (TP) concentrations coincide with lower adiposity and lower risk of developing T2D. This study aims to evaluate the effect of TP on NLRP3 expression in a rodent model of diet-induced obesity (DIO). Methods: C57BL/6J mice were fed ad libitum with a control or a high-fat diet (HFD), added with or without TP (3 g/kg diet), for 11 weeks. IL-1β was quantified in serum, and NLRP3-related gene expression was explored in epididymal adipose tissue. Results: Despite increased weight gain in both high-fat groups, the high-fat TP group gained less weight than the high-fat group. In addition, NLRP3 and caspase-1 expression was higher in the HFD groups, but no differences were observed between the HFD and the HFD TP groups. Serum IL-1β levels were not different among groups. Conclusions: Diet supplementation with TP prevents weight gain and has a neutral influence over NLRP3 expression and IL-1β concentration in a DIO mice model.
Resumen Introducción: Las alteraciones metabólicas como la obesidad y diabetes tipo 2 (DT2) coinciden con la expresión aumentada de factores proinflamatorios. Un complejo que induce la activación de la citocina proinflamatoria IL-1β es el inflamasoma NLRP3 (NOD-like receptor protein 3). Algunos nutrimentos, como los ácidos grasos, influencian los procesos inflamatorios. Por ejemplo, en estudios clínicos, mayores concentraciones del ácido trans-palmitoléico (TP) coinciden con una menor adiposidad y un menor riesgo de desarrollar DT2. El objetivo de este estudio fue evaluar el efecto del TP sobre la expresión del inflamasoma NLRP3 en un modelo de obesidad inducida por dieta (OID) en roedores. Métodos: Se alimentaron ratones C57BL/6J ad libitum con una dieta control o alta en lípidos (AL), adicionada o no con TP (3 g/kg dieta), durante 11 semanas. Se cuantificó la concentración de IL-1β en elsuero de los animales, y en el tejido adiposo epididimal se midió la expresión de los componentes del inflamasoma. Resultados: A pesar del aumento de peso en ambos grupos de dieta con alto contenido en lípidos, el grupo alto en lípidos TP ganó menos peso que el grupo AL. Por otro lado, la expresión de genes del inflamasoma resultó mayor en los grupos AL, pero no se encontraron diferencias entre los grupos AL y AL TP. Además, no se observaron diferencias en la concentración de IL-1β en suero entre grupos. Conclusiones: La dieta suplementada con TP previno el aumento del peso corporal, pero no modificó la expresión de los componentes del inflamasoma ni la concentración de IL-1β en suero.
RESUMEN
The loss of function melanocortin 4-receptor (MC4R) Ile269Asn mutation has been proposed as one of the most important genetic contributors to obesity in the Mexican population. However, whether patients bearing this mutation respond differently to weight loss treatments is unknown. We tested the association of this mutation with obesity in 1683 Mexican adults, and compared the response of mutation carriers and non-carriers to three different weight loss interventions: dietary restriction intervention, phentermine 30 mg/day treatment, and Roux-en-Y gastric bypass (RYGB) surgery. The Ile269Asn mutation was associated with obesity [OR = 3.8, 95% CI (1.5-9.7), p = 0.005]. Regarding interventions, in the dietary restriction group only two patients were MC4R Ile269Asn mutation carriers. After 1 month of treatment, both mutation carriers lost weight: -4.0 kg (-2.9%) in patient 1, and -1.8 kg (-1.5%) in patient 2; similar to the mean weight loss observed in six non-carrier subjects (-2.9 kg; -2.8%). Phentermine treatment produced similar weight loss in six carriers (-12.7 kg; 15.5%) and 18 non-carriers (-11.3 kg; 13.6%) after 6 months of pharmacological treatment. RYGB also caused similar weight loss in seven carriers (29.9%) and 24 non-carriers (27.8%), 6 months after surgery. Our findings suggest that while the presence of a single MC4R loss of function Ile269Asn allele significantly increases obesity risk, the presence of at least one functional MC4R allele seems sufficient to allow short-term weight loss in response to dietary restriction, phentermine and RYGB. Thus, these three different interventions may be useful for the short-term treatment of obesity in MC4R Ile269Asn mutation carriers.
Asunto(s)
Cirugía Bariátrica , Fentermina , Receptor de Melanocortina Tipo 4 , Adulto , Humanos , Mutación , Obesidad/genética , Obesidad/cirugía , Pérdida de Peso/genética , Receptor de Melanocortina Tipo 4/genéticaRESUMEN
The main roles of adipose tissue include triglycerides storage and adipokine secretion, which regulate energy balance and inflammation status. In obesity, adipocyte dysfunction leads to proinflammatory cytokine production and insulin resistance. Bariatric surgery is the most effective treatment for obesity, the gold-standard technique being Roux-en-Y gastric bypass (RYGB). Since metabolic improvements after RYGB are clear, a better understanding of adipose tissue molecular modifications could be derived from this study. Thus, the aim of this systematic review was to find differentially expressed genes in subcutaneous adipose tissue of lean, obese and post-RYGB (distinct timepoints). To address this objective, publications from 2015-2022 reporting gene expression (candidate genes or transcriptomic approach) of subcutaneous adipose tissue from lean and obese individuals before and after RGYB were searched in PubMed, Elsevier, and Springer Link. Excluded publications were reviews, studies analyzing serum, other types of tissues, or bariatric procedures. A risk-of-bias summary was created for each paper using Robvis, to finally include 17 studies. Differentially expressed genes in post-RYGB vs. obese and lean vs. obese were obtained and the intersection among these groups was used for analysis and gene classification by metabolic pathway. Results showed that the lean state as well as the post-RYGB is similar in terms of increased expression of insulin-sensitizing molecules, inducing lipogenesis over lipolysis and downregulating leukocyte activation, cytokine production and other factors that promote inflammation. Thus, massive weight loss and metabolic improvements after RYGB are accompanied by gene expression modifications reverting the "adipocyte dysfunction" phenomenon observed in obesity conditions.
Asunto(s)
Derivación Gástrica , Humanos , Derivación Gástrica/métodos , Grasa Subcutánea , Obesidad/genética , Obesidad/cirugía , Inflamación/genética , Expresión Génica , CitocinasRESUMEN
BACKGROUND: Gut microbiota is a complex organized collection of microorganisms that confers multiple metabolic advantages to the host. The reduced diversity and proportion of specific gut microbial species have been associated with obesity and metabolic disorders. Multidimensional interventions, including modifications in dietary and physical activity habits, are associated with favorable changes in microbiota composition. This pilot study aimed to evaluate changes in the gut microbiota composition of Mexican children with obesity before and after a 6-week multidimensional intervention. METHODS: Blood and stool samples were collected, and anthropometric measurements were obtained from six children with obesity before and after the intervention. The intervention consisted of modeling a hypo energetic diet and giving nutritional and physical activation recommendations. DNA from stool samples was used to characterize gut microbial composition by sequencing the 16S rRNA gene. RESULTS: The decrease in waist circumference was associated with increased Odoribacter relative abundance. However, gut microbiota composition and diversity remained unchanged. CONCLUSIONS: Although no modifications in the body mass index, body fat, composition, or diversity of the gut microbiota were observed with the intervention, it was possible to associate the reduction in waist circumference with the presence of Odoribacter after a multidimensional intervention in Mexican children with obesity.
INTRODUCCIÓN: La microbiota intestinal es un conjunto de microorganismos organizados de forma compleja que confieren múltiples ventajas metabólicas al hospedero. La reducida diversidad y la proporción de ciertas especies sobre otras se ha asociado con obesidad y enfermedades metabólicas. Las intervenciones multidimensionales, que incluyen modificaciones en los hábitos alimentarios y de actividad física, se asocian con cambios favorables en la composición de la microbiota. El objetivo de este estudio piloto fue evaluar la composición de la microbiota intestinal de niños mexicanos con obesidad, antes y después de una intervención multidimensional de seis semanas de duración. MÉTODOS: Se tomaron muestras de sangre y de heces y se realizaron las mediciones antropométricas de seis niños con obesidad, antes y después de la intervención. La intervención consistió en modelar una dieta hipoenergética y dar recomendaciones nutricias y de actividad física. A partir del DNA de las muestras de heces se realizó la caracterización de la microbiota intestinal por secuenciación del gen 16S del RNAr. RESULTADOS: La disminución de la circunferencia de cintura se asoció con un aumento en la abundancia del género Odoribacter. Sin embargo, no se encontraron cambios en la composición de la microbiota intestinal. CONCLUSIONES: A pesar de que la intervención no modificó el índice de masa corporal, masa grasa, composición ni diversidad de la microbiota intestinal, sí se logró asociar la reducción de la circunferencia de cintura con la abundancia de Odoribacter en el presente estudio piloto en niños mexicanos con obesidad.
Asunto(s)
Microbioma Gastrointestinal , Niño , Humanos , Microbioma Gastrointestinal/genética , Proyectos Piloto , ARN Ribosómico 16S/genética , Obesidad , Dieta , Ejercicio FísicoRESUMEN
Obesity is a worldwide epidemic associated with severe health and psychological wellbeing impairments expressed by an increased prevalence of affective disorders. Emotional dysfunction is important due to its effect on social performance. The aim of the present narrative review is to provide a general overview of human research exploring emotional information processing in overweight and obese people. Evidence suggests that obesity is associated with an attenuation of emotional experience, contradictory findings about emotion recognition, and scarce research about automatic emotional information processing. Finally, we made some concluding considerations for future research on emotional information processing in overweight and obese people.
RESUMEN
Abstract Background: Gut microbiota is a complex organized collection of microorganisms that confers multiple metabolic advantages to the host. The reduced diversity and proportion of specific gut microbial species have been associated with obesity and metabolic disorders. Multidimensional interventions, including modifications in dietary and physical activity habits, are associated with favorable changes in microbiota composition. This pilot study aimed to evaluate changes in the gut microbiota composition of Mexican children with obesity before and after a 6-week multidimensional intervention. Methods: Blood and stool samples were collected, and anthropometric measurements were obtained from six children with obesity before and after the intervention. The intervention consisted of modeling a hypo energetic diet and giving nutritional and physical activation recommendations. DNA from stool samples was used to characterize gut microbial composition by sequencing the 16S rRNA gene. Results: The decrease in waist circumference was associated with increased Odoribacter relative abundance. However, gut microbiota composition and diversity remained unchanged. Conclusions: Although no modifications in the body mass index, body fat, composition, or diversity of the gut microbiota were observed with the intervention, it was possible to associate the reduction in waist circumference with the presence of Odoribacter after a multidimensional intervention in Mexican children with obesity.
Resumen Introducción: La microbiota intestinal es un conjunto de microorganismos organizados de forma compleja que confieren múltiples ventajas metabólicas al hospedero. La reducida diversidad y la proporción de ciertas especies sobre otras se ha asociado con obesidad y enfermedades metabólicas. Las intervenciones multidimensionales, que incluyen modificaciones en los hábitos alimentarios y de actividad física, se asocian con cambios favorables en la composición de la microbiota. El objetivo de este estudio piloto fue evaluar la composición de la microbiota intestinal de niños mexicanos con obesidad, antes y después de una intervención multidimensional de seis semanas de duración. Métodos: Se tomaron muestras de sangre y de heces y se realizaron las mediciones antropométricas de seis niños con obesidad, antes y después de la intervención. La intervención consistió en modelar una dieta hipoenergética y dar recomendaciones nutricias y de actividad física. A partir del DNA de las muestras de heces se realizó la caracterización de la microbiota intestinal por secuenciación del gen 16S del RNAr. Resultados: La disminución de la circunferencia de cintura se asoció con un aumento en la abundancia del género Odoribacter. Sin embargo, no se encontraron cambios en la composición de la microbiota intestinal. Conclusiones: A pesar de que la intervención no modificó el índice de masa corporal, masa grasa, composición ni diversidad de la microbiota intestinal, sí se logró asociar la reducción de la circunferencia de cintura con la abundancia de Odoribacter en el presente estudio piloto en niños mexicanos con obesidad.
RESUMEN
Obesity is defined as increased adiposity, which leads to metabolic disease. The growth of adipose tissue depends on its capacity to expand through hyperplasia or hypertrophy, in order to buffer energy surplus. Also, during the establishment of obesity, adipose tissue expansion reflects adipose lipid metabolism (lipogenesis and/or lipolysis). It is well known that dietary factors can modify lipid metabolism promoting or preventing the development of metabolic abnormalities that concur with obesity. Trans-palmitoleic acid (TP), a biomarker of dairy consumption, has been associated with reduced adiposity in clinical studies. Thus, we aimed to evaluate the effect of TP over adiposity and lipid metabolism-related genes in a rodent model of diet-induced obesity (DIO). To fulfil this aim, we fed C57BL/6 mice with a Control or a High-Fat diet, added with or without TP (3 g/kg diet), during 11 weeks. Body weight and food intake were monitored, fat pads were weighted, histology of visceral adipose tissue was analysed and lipid metabolism-related gene expression was explored by qPCR. Results show that TP consumption prevented weight gain induced by high-fat diet, reduced visceral adipose tissue weight and adipocyte size, while increasing the expression of lipolytic molecules. In conclusion, we show for the first time that TP influences adipose tissue metabolism, specifically lipolysis, resulting in decreased adiposity and reduced adipocyte size in a DIO mice model.
Asunto(s)
Adiposidad , Lipólisis , Tejido Adiposo/metabolismo , Animales , Dieta Alta en Grasa/efectos adversos , Ácidos Grasos Monoinsaturados , Ratones , Ratones Endogámicos C57BL , Obesidad/metabolismo , RoedoresRESUMEN
GNPDA2 has been associated with human obesity and type-2 diabetes by using a GWAS approach. GNPDA2 is an enzyme involved in the hexosamine biosynthesis pathway, which is known to be important for nutrient sensing in various organism. Its counter enzyme, GFAT, has previously been shown to be important to the development of insulin resistance in diabetes. The implication of GNPDA2 and GFAT in metabolism is scarce and the effect of both enzymes over appetite and glucose homeostasis is unknown. Aim: Identify the role of GNPDA2 and GFAT in nutrient sensing circuits of the CNS that are important for the regulation of both appetite and glucose homeostasis. Methods: Using Long Evans rats, we administered either a GNPDA2 or GFAT antagonist or vehicle in i3vt. Key Findings: GNPDA2 is highly expressed in hypothalamus and adipose tissue, followed by muscle and liver. GNPDA2 is expressed in different hypothalamic nuclei (ARC, DMH, LHA, PVN). GNPDA2 is downregulated in hypothalamus under diet-induced obesity (as previously described), but GFAT expression does not change. Moreover, i3vt infusion of GNPDA2 or GFAT inhibitor resulted in increased c-Fos in areas related to appetite and glucose homeostasis control as PVN and DMH and to a lesser extent in the LHA and ARC. Central inhibition of GNPDA2 does not alter either acute food intake or body weight; however, GFAT inhibition diminished appetite and body weight due to visceral illness. In addition, central administration of the GNPDA2 antagonist, prior to an intraperitoneal glucose tolerance test, resulted in glucose intolerance in comparison to vehicle without altering insulin levels. Significance: These results suggest that central GNPDA2 does not control appetite, but regulates glucose homeostasis.
RESUMEN
Bariatric surgeries such as the Vertical Sleeve Gastrectomy (VSG) are invasive but provide the most effective improvements in obesity and Type 2 diabetes. We hypothesized a potential role for the gut hormone Fibroblast-Growth Factor 15/19 which is increased after VSG and pharmacologically can improve energy homeostasis and glucose handling. We generated intestinal-specific FGF15 knockout (FGF15INT-KO) mice which were maintained on high-fat diet. FGF15INT-KO mice lost more weight after VSG as a result of increased lean tissue loss. FGF15INT-KO mice also lost more bone density and bone marrow adipose tissue after VSG. The effect of VSG to improve glucose tolerance was also absent in FGF15INT-KO. VSG resulted in increased plasma bile acid levels but were considerably higher in VSG-FGF15INT-KO mice. These data point to an important role after VSG for intestinal FGF15 to protect the organism from deleterious effects of VSG potentially by limiting the increase in circulating bile acids.
Asunto(s)
Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Factores de Crecimiento de Fibroblastos/farmacología , Gastrectomía/efectos adversos , Tejido Adiposo , Animales , Cirugía Bariátrica , Ácidos y Sales Biliares/sangre , Glucemia , Densidad Ósea , Médula Ósea , Diabetes Mellitus Tipo 2 , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Prueba de Tolerancia a la Glucosa , Homeostasis , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad/cirugía , Pérdida de PesoRESUMEN
Obesity is a multifactorial disease in which environmental conditions and several genes play an important role in the development of this disease. Obesity is associated with neurodegenerative diseases (Alzheimer, Parkinson, and Huntington diseases) and with neurodevelopmental diseases (autism disorder, schizophrenia, and fragile X syndrome). Some of the environmental conditions that lead to obesity are physical activity, alcohol consumption, socioeconomic status, parent feeding behavior, and diet. Interestingly, some of these environmental conditions are shared with neurodegenerative and neurodevelopmental diseases. Obesity impairs neurodevelopment abilities as memory and fine-motor skills. Moreover, maternal obesity affects the cognitive function and mental health of the offspring. The common biological mechanisms involved in obesity and neurodegenerative/neurodevelopmental diseases are insulin resistance, pro-inflammatory cytokines, and oxidative damage, among others, leading to impaired brain development or cell death. Obesogenic environmental conditions are not the only factors that influence neurodegenerative and neurodevelopmental diseases. In fact, several genes implicated in the leptin-melanocortin pathway (LEP, LEPR, POMC, BDNF, MC4R, PCSK1, SIM1, BDNF, TrkB, etc.) are associated with obesity and neurodegenerative and neurodevelopmental diseases. Moreover, in the last decades, the discovery of new genes associated with obesity (FTO, NRXN3, NPC1, NEGR1, MTCH2, GNPDA2, among others) and with neurodegenerative or neurodevelopmental diseases (APOE, CD38, SIRT1, TNFα, PAI-1, TREM2, SYT4, FMR1, TET3, among others) had opened new pathways to comprehend the common mechanisms involved in these diseases. In conclusion, the obesogenic environmental conditions, the genes, and the interaction gene-environment would lead to a better understanding of the etiology of these diseases.
RESUMEN
Adipose tissue is an endocrine organ with high metabolic activity. Countless adipose tissue-secreted adipokines and lipokines, as well as peptides and lipids with biological activity have thus far been discovered. Both white and brown and beige adipose tissue are known to contribute to energy homeostasis and metabolic regulation. The purpose of this review is to report on the most recent findings related to adipose tissue according to its color and its relationship with metabolic alterations associated with obesity. After a review of the specialized literature, white, brown and beige adipocyte populations were identified to be able to coexist within the same structure, and to modify global metabolic state in physiological or pathological situations.
El tejido adiposo es un órgano endocrino con gran actividad metabólica. A la fecha se han descubierto innumerables adipocinas y lipocinas, péptidos y lípidos con actividad biológica, secretadas por el tejido adiposo. Se sabe que tanto el tejido adiposo blanco como el pardo y el beige contribuyen a la homeostasis energética y a la regulación metabólica. Esta revisión tiene como finalidad comunicar los hallazgos más recientes relativos al tejido adiposo según su color y la relación de este con las alteraciones metabólicas asociadas con la obesidad. Después de la revisión de la literatura especializada, se identificó que en una misma estructura pueden coexistir poblaciones blancas, pardas y beige, que modifican el estado metabólico global en situaciones fisiológicas o patológicas.
Asunto(s)
Tejido Adiposo Beige , Tejido Adiposo Pardo , Tejido Adiposo Blanco , ColorRESUMEN
Resumen El tejido adiposo es un órgano endocrino con gran actividad metabólica. A la fecha se han descubierto innumerables adipocinas y lipocinas, péptidos y lípidos con actividad biológica, secretadas por el tejido adiposo. Se sabe que tanto el tejido adiposo blanco como el pardo y el beige contribuyen a la homeostasis energética y a la regulación metabólica. Esta revisión tiene como finalidad comunicar los hallazgos más recientes relativos al tejido adiposo según su color y la relación de este con las alteraciones metabólicas asociadas a la obesidad. Después de la revisión de la literatura especializada, se identificó que en una misma estructura pueden coexistir poblaciones blancas, pardas y beige, que modifican el estado metabólico global en situaciones fisiológicas o patológicas.
Abstract Adipose tissue is an endocrine organ with high metabolic activity. Countless adipose tissue-secreted adipokines and lipokines, as well as peptides and lipids with biological activity have thus far been discovered. Both white and brown and beige adipose tissue are known to contribute to energy homeostasis and metabolic regulation. The purpose of this review is to report on the most recent findings related to adipose tissue according to its color and its relationship with metabolic alterations associated with obesity. After a review of the specialized literature, white, brown and beige adipocyte populations were identified to be able to coexist within the same structure, and to modify global metabolic state in physiological or pathological situations.
Asunto(s)
Tejido Adiposo Pardo , Tejido Adiposo Blanco , Tejido Adiposo Beige , ColorRESUMEN
INTRODUCTION: The Food Disgust Scale (FDS) was recently developed and validated in Swiss adult population. This study aims to: (1) validate the FDS for the first time in a Spanish-speaking Mexican population, (2) correlate food disgust sensitivity with picky eating measures, and (3) explore the association between food disgust sensitivity and body mass index (BMI). MATERIALS AND METHODS: A Spanish version of the FDS (FDS-Sp) and its short version (FDS-Sp short) were tested with confirmatory factor analysis (CFA) in order to test the original item/factor structure. Bivariate correlations were performed to determine the association between FDS-Sp/FDS-Sp short scores and picky eating. Lastly, hierarchical linear regression analysis was carried out to determine the relationship between food disgust sensitivity and BMI. RESULTS: The factor structure of the FDS was replicated and acceptable internal consistency values were observed for FDS-Sp subscales (α varied between 0.781 and 0.955). Moreover, FDS-Sp subscales and FDS-Sp short were correlated with picky eating. Higher score in VEGI subscale of the FDS-Sp was a significant predictor for higher BMI, explaining 4% of the variance. CONCLUSION: FDS-Sp is a useful, reliable and robust psychometric instrument to measure the sensitivity to unpleasant food situations in a Mexican adult Spanish-speaking population. A relationship between food disgust sensitivity and picky eating, selective eating behaviors and neophobia in Mexicans was confirmed. BMI is multifactorial and only one subscale of FDS-Sp is a significant predictor for BMI status. These results are helpful to continue exploring food disgust in diverse populations.
RESUMEN
Obesity prevalence has increased in the last decades worldwide leading to metabolic complications, such as type 2 diabetes, steatosis, cardiovascular disease, among others; its development is influenced by genetic factors and environmental factors, such as intestinal microbiome. In Mexico, 33.3% of the adults present this disease. Obesity is defined as an excessive adipose tissue accumulation, provoking its dysfunction. Adipose tissue remodeling, which involves angiogenesis, hypoxia and inflammation, is implicated in the developing of obesity and metabolic modifications. Bariatric surgery is the most used and successful intervention to control morbid obesity, leading a maintained loss of weight and remission of some of its comorbidities as type 2 diabetes. Here, we review some of the molecular aspects of the metabolic changes provoked by bariatric surgery and its impact in weight loss and comorbidities remission. In summary, this article reviews the genetic aspects, microbiome and molecular facts (adipose tissue remodeling) that are involved in obesity development. In addition, some of the molecular aspects about bariatric surgery are described and the mechanisms that are regulated to control obesity and its comorbidities.
En las últimas décadas, la prevalencia de la obesidad ha aumentado a escala mundial y ha provocado complicaciones metabólicas tales como diabetes de tipo 2, esteatosis, problemas cardiovasculares, entre otras. Su desarrollo puede estar influenciado por factores genéticos y ambientales, incluyendo la microbiota intestinal. En México, el 33.3% de la población adulta padece de este problema. La obesidad involucra un incremento excesivo del tejido adiposo que produce su disfunción. Se ha demostrado que la remodelación del tejido adiposo, dada por angiogénesis, hipoxia e inflamación, otorga susceptibilidad a desarrollar obesidad y conlleva a modificaciones metabólicas. La cirugía bariátrica ha sido el procedimiento más utilizado y más exitoso para tratar la obesidad mórbida en cuanto a la pérdida de peso corporal a largo plazo y a la remisión de comorbilidades como la diabetes tipo 2. En este artículo se revisan los aspectos moleculares por medio de los cuales la cirugía bariátrica provoca cambios metabólicos que se reflejan en la pérdida de peso y las mejoras metabólicas. Por lo tanto, se resumen aspectos genéticos, de microbioma y moleculares (remodelación del tejido adiposo) que influyen en el desarrollo de la obesidad. También se explican los aspectos moleculares a través de los cuales se puede modular la pérdida de peso y la mejoría de comorbilidades metabólicas.
Asunto(s)
Tejido Adiposo/metabolismo , Cirugía Bariátrica/métodos , Obesidad Mórbida/epidemiología , Adulto , Animales , Humanos , Enfermedades Metabólicas/epidemiología , Enfermedades Metabólicas/etiología , México/epidemiología , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/cirugía , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Prevalencia , Pérdida de PesoRESUMEN
Resumen En las últimas décadas, la prevalencia de la obesidad ha aumentado a escala mundial y ha provocado complicaciones metabólicas tales como diabetes de tipo 2, esteatosis, problemas cardiovasculares, entre otras. Su desarrollo puede estar influenciado por factores genéticos y ambientales, incluyendo la microbiota intestinal. En México, el 33.3% de la población adulta padece de este problema. La obesidad involucra un incremento excesivo del tejido adiposo que produce su disfunción. Se ha demostrado que la remodelación del tejido adiposo, dada por angiogénesis, hipoxia e inflamación, otorga susceptibilidad a desarrollar obesidad y conlleva a modificaciones metabólicas. La cirugía bariátrica ha sido el procedimiento más utilizado y más exitoso para tratar la obesidad mórbida en cuanto a la pérdida de peso corporal a largo plazo y a la remisión de comorbilidades como la diabetes tipo 2. En este artículo se revisan los aspectos moleculares por medio de los cuales la cirugía bariátrica provoca cambios metabólicos que se reflejan en la pérdida de peso y las mejoras metabólicas. Por lo tanto, se resumen aspectos genéticos, de microbioma y moleculares (remodelación del tejido adiposo) que influyen en el desarrollo de la obesidad. También se explican los aspectos moleculares a través de los cuales se puede modular la pérdida de peso y la mejoría de comorbilidades metabólicas.
Abstract Obesity prevalence has increased in the last decades worldwide leading to metabolic complications, such as type 2 diabetes, steatosis, cardiovascular disease, among others; its development is influenced by genetic factors and environmental factors, such as intestinal microbiome. In Mexico, 33.3% of the adults present this disease. Obesity is defined as an excessive adipose tissue accumulation, provoking its dysfunction. Adipose tissue remodeling, which involves angiogenesis, hypoxia and inflammation, is implicated in the developing of obesity and metabolic modifications. Bariatric surgery is the most used and successful intervention to control morbid obesity, leading a maintained loss of weight and remission of some of its comorbidities as type 2 diabetes. Here, we review some of the molecular aspects of the metabolic changes provoked by bariatric surgery and its impact in weight loss and comorbidities remission. In summary, this article reviews the genetic aspects, microbiome and molecular facts (adipose tissue remodeling) that are involved in obesity development. In addition, some of the molecular aspects about bariatric surgery are described and the mechanisms that are regulated to control obesity and its comorbidities.