Analysis of Adrenergic Receptors during the Onset and Progression of Metabolic Syndrome

Abstract

Male C57BL/6J mice fed with high fat simple carbohydrate (HFSC) diet were used as the newlinemodel to study the adrenergic receptors (AR) during the onset and development of metabolic newlinesyndrome (MetS). A detailed profiling of ARs in the brainstem, hypothalamus and pancreas newlinewas undertaken using radioreceptor assays, gene expression studies, cAMP analysis and p- newlineCREB analysis. A preliminary study was also undertaken to assess the effect of sympathetic newlineactivation in the liver and kidney of this model. Also, the role of ARs in leptin secretion from newlineadipose tissue explants was studied using an in vitro approach. newlineA reduction in the density of ARs along with altered affinity of and#945; and and#946; ARs was observed in newlinethe brainstem of HFSC fed mice. Gene expression studies revealed that the adrenergic newlinereceptor genes were upregulated in the brainstem of HFSC fed mice. However, there was no newlinesignificant change in the cAMP content. It was observed that Adra1a, Adra1b, Adra1d, newlineAdra2a, Adra2b, Adra2c and Adrb1 genes were downregulated and Adrb2 gene was newlineupregulated in the hypothalamus of HFSC fed mice. The analysis of cAMP content did not newlineshow any significant change. However, increased expression of p-CREB was observed in the newlinehypothalamus of HFSC fed mice. The gene expression study of whole pancreas of HFSC fed newlinemice showed downregulation of Adra1a, Adra1d, Adra2b, Adra2c and Adrb1 genes along newlinewith upregulation of Adra2a and Adrb3 genes. This was accompanied by low cAMP levels newlineand p-CREB expression. newlineHistopathological analysis of the liver of HFSC fed mice showed signs of non alcoholic fatty newlineliver disease (NAFLD), whereas that of the kidney of HFSC fed mice did not show any newlinecharacteristic feature of chronic kidney disease associated with MetS. Further, analysis of newlineurinary total protein did not show any significant levels of protein. In vitro leptin secretion newlinestudies revealed that and#945; ARs have a stimulatory role in leptin secretion and and#946; ARs were non newlineresponsive in adipose tissue explants of male C57BL/6J mice fed with HFSC diet. newlineThese studies on ARs c