The role and mechanism of hypothalamus in the cause of obesity caused by chronic glucocorticoids.

Recently, the Chinese Academy of Sciences Shanghai Institute of Life Sciences (population health field) nutrition metabolism and food safety key laboratory Guo Extraordinary group research paper, with SGK1/FOXO3 signaling in hypothalamic POMC s neurons s cucocorticoid-asd adiposity, published online in Diabetes, the study found that the hypothalamus in chronic glucocortic corticosteroids caused by obesity role and mechanism.
corticosteroids, named for secretion by the adrenal cortex and regulating sugar metabolism, it plays an important role in regulating the development, growth, metabolism and immune function of the body, is the most important regulatory hormone of the body's stress response, and is also the most widely used and effective clinical anti-inflammatory, anti-shock drugs and immunosuppressants.
these drugs are very effective, but there are many side effects, such as abnormal accumulation of adipose tissue.
patients who have been taking the drug for a long time are shown to be centripetal obesity, and the regulatory mechanisms remain unclear.
hypothalamus is an integral part of the interbrain and is the center of regulation of internal and endocrine activity.
in the hethrithal cerebral arch nucleus (ARC), there are two types of neurons that regulate energy metabolism: one is the appetite-boosting hedgehog peptide gene-related protein (AgRP) neurons; and the other is the appetite-suppressing ahexalysin (POMC) neuron.
POMC neurons affect the body's energy consumption by releasing the shear product of alebum -alpha-MSH, which suppresses appetite on the one hand, and regulates the excitability of the sympathetic nervous system on the other.
and there have been no reports of obesity caused by specific neurons such as POMC and how to regulate glucocorticoids.
, under the guidance of Shanghai Academy of Health researcher Guo Extraordinary, Ph.D. student Deng Yaxuan and others found that although serum and glucocorticoid regulating kinase 1 (SGK1) is a classic downstream of dexamethasone activation, but its expression in POMC neurons can be inhibited by chronic dessemin treatment.
this suggests that SGK1 may play an important role in glucocorticoid-induced obesity in POMC neurons.
researchers used tissue-specific gene knockout techniques to specifically knock out the SGK1 gene in fertilized eggs and POMC neurons in adult mice.
analysis found that these gene knockout mice can simulate chronic dessemin-induced obesity and reduced energy consumption.
, in contrast, the continuous overexpression of SGK1 in POMC neurons in mice will appear opposite phenotypes and can alleviate chronic dessemin-induced obesity.
further exploration of its mechanism of action found that dexamethasone reduced the expression of pomc of the hypothalamus and the content of alpha-MSH through the SGK1/FOXO3 signaling pathway, and that the injection of alpha-MSH in the ventricles or the use of adenovirus-mediated arch-like nuclear site FOXO3 beat slower can greatly reverse the metabolic phenotyptype of SGK1 knockout mice.
the study found that SGK1/FOXO3 signals regulate the important function of glucocorticoid-induced obesity in the pomacic POMC neurons, providing new insights and ideas for understanding the relationship between glucocorticoids and the accumulation of abnormal fat, and suggesting that sGK1/FOXO3 signals in the hypothalamus may be a potential target for the treatment of obesity and related metabolic diseases.
research work has been supported by the National Natural Science Foundation of China, the Shanghai Science and Technology Commission and the Chinese Academy of Sciences and other scientific research funds.
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