Using the mouse modle to study the effects of hyperleptinemia and hyperglycemia due to obesity on adrenocortical function
Date Issued
2008
Date
2008
Author(s)
Tsai, Hsun-Hsun
Abstract
Obesity is regarded as a kind of chronic metabolic disease and recently the prevalence of obesity is rapidly increasing in the development countries. Obesity is caused by energy imbalance that may lead to storage of excess fat in the form of triglyceride in adipocytes; and make those cells become hyperplasia and dysfunctional. The concequences of dysfunction in adipocytes include hyperglycemia which leads to diabetes mellitus and elevated production of adipokines such as leptin. Serum leptin levels are direct proportion to the body mass index (BMI) in human beings. Several studies have been presented that serum cortisol levels are lower in people with high waist-to-hip ratio (WHR) after adrenocorticotropin (ACTH) or corticotrophin releasing hormone (CRH) stimulation test compared with those with normal WHR. These studies imply that obesity may influence the function of adrenal cortex. Some studies observed that leptin was able to decrease the secretion of steroid hormones and inhibit the expressions of steroidogenic proteins in NCI-H295 cells. Recently, it was observed that diabetic patients have elevated serum/urine cortisol levels and the activities of their hypothalamo-pituitary-adrenocortical axis are out of control. This study is going to detect the effect of obesity on the adrenal cortex and the effects of the key factors associated with obesity, leptin and glucose on regulation of steroidogenesis.uercetin is a kind of flavnoid and has been found playing as a broad protein kinase inhibitors such as JAK2 or PI3K which are involved in leptin signal transduction pathway. Rosiglitazone, a kind of PPARγ agonist is used as an antidiabetic drug recently in human beings. We fed mice with quercetin to study if it could influence the adrenal cortex function in obese mice by blocking the signal transduction pathway of leptin and fed mice with rosiglitazone to study if it could influence the adrenal cortex function in obese mice by normalizing their blood glucose levels.he results of our in vitro studies showed that leptin and high-level glucose decreased the secretion of steroid hormones and depressed the expression of steroidogenic proteins, both StAR and P450scc in adrenal cells, but quercetin could reverse these effects of leptin on steroidgenesis in cells. Our in vivo studies indicated that after ACTH stimulation test the serum corticosterone levels of obese mice were lower than which of normal-weighted ones. Besides this, the basal corticosterone levels during 24 hours in urine of obese mice were lower than normal-weighted ones, although which of normal-weighted mice were decreased by age. Feeding mice with quercetin for 14 days or for 30 days, using ACTH stimulating tests, we found that corticosterone levels and the expression of steroidogenic protein, StAR in obese mice were increased by quercetin. After feeding mice with rosiglitazone for 30 days, the corticosterone levels in urine of obese ones were elevated.n conclusions, this study demonstrated that the secretion of steroid hormones and the expression of steroidogenic proteins, both StAR and P450scc were inhibited by leptin and high-level of glucose in adrenal cells and the function of adrenal cortex in obese mice induced with high-fat-diet was impaired. However, the mechanisms of the effects of hyperleptinemia and hyperglycemia on causing dysfunction of adrenal cortex in obese mice still remains unclear and requires more detailed studies.
Subjects
obesity
leptin
hyperglycemia
adrenocortical function
quercetin
SDGs
Type
thesis
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