Impact of MR on mature adipocytes in high-fat/high-sucrose diet-induced obesity

Abstract

Active glucocorticoid levels are elevated in the adipose tissue of obesity due to the enzyme 11beta-hydroxysteroid dehydrogenase type 1. Glucocorticoids can bind and activate both glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), and pharmacological blockades of MR prevents high-fat diet-induced obesity and glucose intolerance. To determine the significance of MR in adipocytes, we generated adipocyte-specific MR knockout mice (AdipoMR-KO) and fed them high-fat/high-sucrose diet. We found that adipocyte-specific deletion of MR did not affect the body weight, fat weight, glucose tolerance, or insulin sensitivity. While liver weight was slightly reduced in AdipoMR-KO, there were no significant differences in the mRNA expression levels of genes associated with lipogenesis, lipolysis, adipocytokines, and oxidative stress in adipose tissues between the control and AdipoMR-KO mice. The results indicated that MR in mature adipocytes plays a minor role in the regulation of insulin resistance and inflammation in high-fat/high-sucrose diet-induced obese mice.

Mice lacking PLAP-1/asporin counteracts high fat diet-induced metabolic disorder and alveolar bone loss by controlling adipose tissue expansion

“…was performed according to a previously published protocol 19 with modifications. Minced adipose tissue from WT and Plap-1 KO mice was digested in D-MEM supplemented with 4000 units/ml type II collagenase from Clostridium histolyticum (Sigma-Aldrich, Missouri, USA), 0.1 mg/ml DNase I (Roche, Basel, Switzerland), 10% FBS and 60 μg/ml of kanamycin at 37ºC for 30 min.…”

Aldosterone/MR Signaling, Oxidative Stress, and Vascular Dysfunction

“…In vivo conditional upregulation of MR in mouse adipocytes led to increased production of H 2 O 2 from epididymal adipose tissue likely due to the decrease in catalase mRNA levels and the increased Nox-4 mRNA levels without changes in Nox-1 and Nox-2 expressions which likely explain changes in vascular contractility [84]. Interestingly, adipocyte-specific MR knockout mice (AdipoMR-KO) fed with high-fat/high-sucrose diet showed similar levels of 8-isoprostane, p22phox, SOD-1, or catalase mRNA levels, and they did not show differences in body weight, fat weight, glucose tolerance, insulin sensitivity, or inflammation [85]. Similar results were reported by Feraco and coworkers [86] using inducible adipocyte-specific deletion of MR fed a 45% high-fat diet although in this study oxidative stress was not evaluated.…”

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“…La sobreexpresión condicional del MR en adipocitos murinos dio lugar a una incrementada producción de H 2 O 2 del tejido adiposo epididimal probablemente debido a una disminución en la expresión del gen de la catalasa y un aumento en la expresión de los niveles de Nox4 sin cambios en las expresiones de Nox1 o Nox2, hallazgos que probablemente explican los cambios en la contractilidad vascular encontrados en este modelo (84). Curiosamente, ratones knockout para MR específicos de adipocitos cuando se alimentaron con una dieta alta en grasa y en sacarosa, mostraron niveles similares del marcador de estrés oxidativo 8-isoprostano, o de los genes de p22phox, SOD-1 o catalasa, y además, no mostraron diferencias en el peso corporal, peso de la grasa, tolerancia a la glucosa, sensibilidad a la insulina o inflamación (85). Resultados similares han sido publicados recientemente por Feraco y cols (86) utilizando un modelo de deleción inducible de MR específica de adipocitos cuanto se les alimentó con una dieta alta en grasa (45 %), aunque es importante destacar que en este estudio el estrés oxidativo no fue evaluado.…”