Deletion of liver-specific STAT5 gene alters the expression of bile acid metabolism genes and reduces liver damage in lithogenic diet-fed mice

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• 作者：Myunggi Baik^a ; ^b ; ¹ ; ^{mgbaik@snu.ac.kr} ; ^{mgbaik2164@naver.com} ; Jangseon Kim^c ; ¹ ; Min Yu Piao^a ; Hyeok Joong Kang^a ; Seung Ju Park^a ; Sang Weon Na^a ; Sung-Hoon Ahn^d ; Jae-Hyuk Lee^e
• 关键词：STAT5 ; signal transducer and activator of transcription 5 ; GH ; growth hormone ; IGF-1 ; insulin-like growth factor-1 ; LDLR ; low-density lipoprotein receptor ; STAT5 LKO ; liver-specific STAT5 knock-out ; STAT5 fl/fl ; STAT5 flox/flox ; TG ; triacylglycerol ; ChMCs ; cholesterol monohydrate crystals ; H&E ; hematoxylin and eosin ; ORO ; Oil-Red O ; CA ; cholic acid ; CDCA ; chenodeoxycholic acid ; DCA ; deoxycholic acid ; TCA ; taurocholic acid ; TCDCA ; tauro chenodeoxycholic acid ; TDCA ; taurodeoxycholic acid ; GCA ; gly
• 刊名：The Journal of Nutritional Biochemistry
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：39
• 期：Complete
• 页码：59-67
• 全文大小：1092 K
• 卷排序：39

文摘

Signal transducers and activators of transcription 5 (STAT5) mediates growth hormone signals, which may control hepatic cholesterol uptake and bile acid metabolism. Deregulation of liver cholesterol homeostasis and bile acid metabolism may cause liver damage and cholesterol gallstone development. The purpose of this study was to understand the role of local STAT5 signaling in cholesterol and bile acid metabolism using liver-specific STAT5 knock-out (STAT5 LKO) mice on a normal diet and a cholesterol- and bile acid-containing lithogenic diet. STAT5 LKO mice showed significant down-regulation of STAT5 and insulin-like growth factor-1 genes. STAT5 gene deletion had a minor effect on cholesterol metabolism, as evidenced by a minor change in circulating cholesterol levels and no changes in expression of hepatic low-density lipoprotein receptor and cholesterol synthesis genes in STAT5 LKO mice. In contrast, bile acid synthesis and uptake genes were profoundly down-regulated and bile acid detoxification genes were up-regulated in STAT5 LKO mice. In STAT5 fl/fl mice, a lithogenic diet induced liver damage, as evidenced by moderate increases in liver ballooning, inflammation and fibrosis. However, STAT5 deletion ameliorated the degree of liver damage induced by the lithogenic diet. In STAT5 LKO mice, a lithogenic diet did not alter the incidence or severity of cholesterol gallstones. In conclusion, local STAT5 signaling does not have a significant role in cholesterol metabolism. In contrast, hepatic STAT5 signaling has significant roles in regulating transcription of genes for synthesis, transport and detoxification of bile acids, but it has only a minor role in bile acid metabolism.