RESUMEN
Worldwide, childhood obesity cases continue to rise, and its prevalence is known to increase the risk of non-communicable diseases typically found in adults, such as cardiovascular disease and type 2 diabetes mellitus. Thus, comprehending its multiple causes to build healthier approaches and revert this scenario is urgent. Obesity development is strongly associated with high fructose intake since the excessive consumption of this highly lipogenic sugar leads to white fat accumulation and causes white adipose tissue (WAT) inflammation, oxidative stress, and dysregulated adipokine release. Unfortunately, the global consumption of fructose has increased dramatically in recent years, which is associated with the fact that fructose is not always evident to consumers, as it is commonly added as a sweetener in food and sugar-sweetened beverages (SSB). Therefore, here, we discuss the impact of excessive fructose intake on adipose tissue biology, its contribution to childhood obesity, and current strategies for reducing high fructose and/or free sugar intake. To achieve such reductions, we conclude that it is important that the population has access to reliable information about food ingredients via food labels. Consumers also need scientific education to understand potential health risks to themselves and their children.
Asunto(s)
Diabetes Mellitus Tipo 2 , Obesidad Infantil , Niño , Adulto , Humanos , Obesidad Infantil/epidemiología , Obesidad Infantil/etiología , Obesidad Infantil/prevención & control , Tejido Adiposo , Tejido Adiposo Blanco , Fructosa/efectos adversosRESUMEN
BACKGROUND: Obesity is a worldwide concern due to its global rapid expansion and remarkable impact on individual's health by predisposing to several other diseases. About twice as many women as men suffer from severe obesity and, in fact, there are stages in a woman's life when weight gain and adiposity can result in greater damage to health. For example, obesity triples the chance of a woman developing gestational diabetes. Many hormones promote the metabolic adaptations of pregnancy, including progesterone, whose role in female obesity is still not well known despite being involved in many physiological and pathological processes. METHODS: Here we investigated whether progesterone treatment at low dose can worsen the glucose metabolism and the morpho functional aspects of adipose tissue and pancreas in obese females. Mice were assigned into four groups: normocaloric diet control (NO-CO), high-fat and -fructose diet control (HFF-CO), normocaloric diet plus progesterone (NO-PG) and high-fat and -fructose diet plus progesterone (HFF-PG) for 10 weeks. Infusion of progesterone (0.25 mg/kg/day) was done by osmotic minipump in the last 21 days of protocol. RESULTS: Animals fed a hypercaloric diet exhibited obesity with increased body weight (p < 0.0001), adipocyte hypertrophy (p < 0.0001), hyperglycemia (p = 0.03), and glucose intolerance (p = 0.001). HFF-CO and HFF-PG groups showed lower adiponectin concentration (p < 0.0001) and glucose-stimulated insulin secretion (p = 0.03), without differences in islet size. Progesterone attenuated glucose intolerance in the HFF-PG group (p = 0.03), however, did not change morphology or endocrine function of adipose tissue and pancreatic islets. CONCLUSIONS: Taken together, our results showed that low dose of progesterone does not worsen the effects of hypercaloric diet in glycemic metabolism, morphology and function of adipose tissue and pancreatic islets in female animals. These results may improve the understanding of the mechanisms underlying the pathogenesis of obesity in women and eventually open new avenues for therapeutic strategies and better comprehension of the interactions between progesterone effects and obesity.
Asunto(s)
Intolerancia a la Glucosa , Islotes Pancreáticos , Humanos , Masculino , Embarazo , Femenino , Ratones , Animales , Progesterona , Intolerancia a la Glucosa/complicaciones , Intolerancia a la Glucosa/patología , Ratones Obesos , Dieta Alta en Grasa/efectos adversos , Obesidad/metabolismo , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/patología , Tejido Adiposo/metabolismo , Aumento de Peso , Fructosa , Ratones Endogámicos C57BL , Insulina/metabolismoRESUMEN
Obesity is associated with increased risk of several chronic diseases and the loss of disease-free years, which has increased the focus of much research for the discovery of therapy to combat it. Under healthy conditions, women tend to store more fat in subcutaneous deposits. However, this sexual dimorphism tends to be lost in the presence of comorbidities, such as type 2 diabetes mellitus (T2DM). Aerobic physical exercise (APE) has been applied in the management of obesity, however, is still necessary to better understand the effects of APE in obese female. Thus, we investigated the effect of APE on body weight, adiposity, exercise tolerance and glucose metabolism in female ob/ob mice. Eight-weeks-old female wild-type C57BL/6J and leptin-deficient ob/ob mice (Lepob) were distributed into three groups: wild-type sedentary group (Wt; n = 6), leptin-deficient sedentary group (LepobS; n = 5) and leptin-deficient trained group (LepobT; n = 8). The LepobT mice were subjected to 8 weeks of aerobic physical exercise (APE) at 60% of the maximum velocity achieved in the running capacity test. The APE had no effect in attenuating body weight gain, and did not reduce subcutaneous and retroperitoneal white adipose tissue (SC-WAT and RP-WAT, respectively) and interscapular brown adipose tissue (iBAT) weights. The APE neither improved glucose intolerance nor insulin resistance in the LepobT group. Also, the APE did not reduce the diameter or the area of RP-WAT adipocytes, but the APE reduced the diameter and the area of SC-WAT adipocytes, which was associated with lower fasting glycemia and islet/pancreas area ratio in the LepobT group. In addition, the APE increased exercise tolerance and this response was also associated with lower fasting glycemia in the LepobT group. In conclusion, starting APE at a later age with a more severe degree of obesity did not attenuate the excessive body weight gain, however the APE promoted benefits that can improve the female health, and for this reason it should be recommended as a non-pharmacological therapy for obesity.
Asunto(s)
Glucemia , Peso Corporal/fisiología , Tolerancia al Ejercicio/fisiología , Obesidad/fisiopatología , Condicionamiento Físico Animal/fisiología , Animales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Ratones , Obesidad/sangreRESUMEN
Fish oil supplementation has been reported to be generally beneficial in autoimmune, inflammatory and cardiovascular disorders. Most researchers have attributed these beneficial effects to the high content of omega-3 fatty acids in fish oil (FO). The effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are not differentiated in most studies. In fact, up to 1990, purified DHA was not available for human use and there was no study regarding its effects on human immune response. In this review, the differences in the effects of these two fatty acids on cell function are discussed. Studies have shown that EPA and DHA have also different effects on leukocyte functions such as phagocytosis, chemotactic response and cytokine production. DHA and EPA modulate differently expression of genes in lymphocytes. Activation of intracellular signaling pathways involved with lymphocyte proliferation is also differently affected by these two fatty acids. In relation to insulin producing cell line RINm5F, DHA and EPA are cytotoxic at different concentrations and the proteins involved with cell death are differently modulated by these two fatty acids. Substantial improvement in the therapeutic usage of omega-3 fatty acid-rich FO will be possible with the discovery of the different mechanisms of actions of DHA and EPA.
Asunto(s)
Ácidos Docosahexaenoicos/farmacología , Ácidos Eicosanoicos/farmacología , Aceites de Pescado/farmacología , Animales , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/fisiopatología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Humanos , Sistema Inmunológico/efectos de los fármacos , Leucocitos/efectos de los fármacos , Leucocitos/metabolismoRESUMEN
The aim of this study was to investigate whether the toxicity of saturated and polyunsaturated fatty acids (PUFA) on RINm5F cells is related to the phosphorylation state of Akt, ERK and PKC delta. The regulation of these kinases was compared in three experimental designs: (a) 4h-exposure, (b) 4h-exposure and a subsequent withdrawn of the FA for a 20 h period and (c) 24h-exposure. Saturated and PUFA were toxic to RINm5F cells even at low concentrations. Also, evidence is provided for a late (i.e. the effect only appeared hours after the treatment) and a persistent regulation (i.e. maintenance of the effect for several hours) of Akt, ERK and PKC delta phosphorylation by the FA. Late activation of PKC delta seems important for palmitate cytotoxicity. Persistent activation of the survival proteins Akt and ERK by stearate, oleate and arachidonate might play an important role to prevent the toxic effect of posterior PKC delta activation. The results shown may explain why a short-period exposure to FA is not enough to induce cytotoxicity in pancreatic beta-cells, since survival pathways are activated. Besides, when this activation is persistent, it may overcome a posterior induction of death pathways.
Asunto(s)
Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Ácidos Grasos Insaturados/toxicidad , Ácidos Grasos/toxicidad , Células Secretoras de Insulina/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Activación Enzimática/fisiología , Quinasas MAP Reguladas por Señal Extracelular/efectos de los fármacos , Ácidos Grasos/administración & dosificación , Ácidos Grasos Insaturados/administración & dosificación , Células Secretoras de Insulina/enzimología , Insulinoma/metabolismo , Fosforilación/efectos de los fármacos , Proteína Quinasa C-delta/efectos de los fármacos , Proteína Quinasa C-delta/metabolismo , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Ratas , Factores de TiempoRESUMEN
Fatty acids have been shown to cause death of rat and human primary pancreatic beta cells and of insulin-producing cell lines. These studies focused mainly on saturated and monounsaturated FA such as palmitic, stearic and oleic acids. In this study, we have performed a comparison of the toxicity of a wider range of FA. The toxicity of different FA to insulin-producing RINm5F cells was assessed by flow cytometry measuring loss of plasma membrane integrity and increase in DNA fragmentation. Additionally, the FA induced neutral lipid accumulation and the FA composition were determined. Palmitic, linoleic, gamma-linolenic, oleic, stearic, and eicosapentaenoic acid caused DNA fragmentation of insulin-producing RINm5F cells. Loss of membrane integrity was mainly caused by linoleic and gamma-linolenic acid. There was no correlation between cytotoxicity and the abundance of the FA in the cells as determined by HPLC analysis. Taken as whole, the toxic effect of the FA on insulin-producing RINm5F cells varied irrespective of the chain length and the degree of unsaturation. In these cells PA and LA exhibited the highest toxicity, whereas AA was not toxic. In addition, the toxicity of most tested FA was inversely related to low NLA, except for AA and EPA. The results of this study contribute to the understanding of the role of FA in the impairment of pancreatic beta cell function that occurs in type 2 diabetes and obesity.
Asunto(s)
Ácidos Grasos/toxicidad , Insulina/biosíntesis , Lípidos/análisis , Animales , Ácido Araquidónico/análisis , Ácido Araquidónico/toxicidad , Línea Celular Tumoral , Membrana Celular/química , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Fragmentación del ADN/efectos de los fármacos , Ácidos Docosahexaenoicos/análisis , Ácidos Docosahexaenoicos/toxicidad , Relación Dosis-Respuesta a Droga , Ácido Eicosapentaenoico , Ácidos Grasos/análisis , Ácidos Grasos Insaturados/análisis , Ácidos Grasos Insaturados/toxicidad , Citometría de Flujo/métodos , Insulinoma/metabolismo , Insulinoma/patología , Ácido Linoleico/análisis , Ácido Linoleico/toxicidad , Lípidos/química , Ácido Oléico/análisis , Ácido Oléico/toxicidad , Ácido Palmítico/análisis , Ácido Palmítico/toxicidad , Ratas , Ácidos Esteáricos/análisis , Ácidos Esteáricos/toxicidad , Ácido gammalinolénico/análisis , Ácido gammalinolénico/toxicidadRESUMEN
An important challenge for both students and teachers of physiology is to integrate the different areas in which physiological knowledge is didactically divided. In developing countries, such an issue is even more demanding, because budget restrictions often affect the physiology program with laboratory classes being the first on the list when it comes to cuts in expenses. With the aim of addressing this kind of problem, the graduate students of our department organized a physiology summer course offered to undergraduate students. The objective was to present the different physiological systems in an integrated fashion. The strategy pursued was to plan laboratory classes whose experimental results were the basis for the relevant theoretical discussions. The subject we developed to illustrate physiology integration was the study of factors influencing salivary secretion.