Tao Wu1, Yu-hua Liu1, Yu-cai Fu2, Xing-mu Liu3, Xiao-hui Zhou4. 1. Department of Lemology, the First Affiliated Hospital of Shantou University Medical College, Shantou Laboratory of Cell Senescence, Shantou University Medical College, Shantou. 2. Laboratory of Cell Senescence, Shantou University Medical College, Shantou. 3. Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Shantou University Medical College, Shantou, China. 4. Department of Lemology, the First Affiliated Hospital of Shantou University Medical College, Shantou southernice@126.com.
Abstract
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become the most common form of chronic liver disease in the world. Recent studies in cultured cells and mice have shown that sirtuin, especially sirtuin 1 (SIRT1), is a key metabolic sensor for regulating metabolic homeostasis and thus has the potential to ameliorate NAFLD. For the purposes of this study, we hypothesized that the inhibition of sirtuin signaling might contribute to the development of NAFLD. METHODS: Tissue was obtained from hepatectomy specimens (10 samples), and medicolegal autopsies (10 samples). Liver tissue sections were stained with H&E. Expression of sirtuin in liver tissues in NAFLD and control group was investigated by RT-PCR and Western blotting. RESULTS: RT-PCR and Western blotting demonstrated decreased expression of SIRT1, SIRT3, SIRT5, and SIRT6 in the NAFLD group in comparison with the control group. Increased expression of lipogenic genes including sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthase (FASN), and acetyl-CoA carboxylase (ACC) was noted within the NAFLD group. In contrast to the other SIRT genes, the expression of SIRT4 was upregulated. CONCLUSION: Our study provides direct evidence of the downregulation of sirtuin signaling that suppresses lipid synthesis in the liver of NAFLD patients, which may promote NAFLD development.
BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) has become the most common form of chronic liver disease in the world. Recent studies in cultured cells and mice have shown that sirtuin, especially sirtuin 1 (SIRT1), is a key metabolic sensor for regulating metabolic homeostasis and thus has the potential to ameliorate NAFLD. For the purposes of this study, we hypothesized that the inhibition of sirtuin signaling might contribute to the development of NAFLD. METHODS: Tissue was obtained from hepatectomy specimens (10 samples), and medicolegal autopsies (10 samples). Liver tissue sections were stained with H&E. Expression of sirtuin in liver tissues in NAFLD and control group was investigated by RT-PCR and Western blotting. RESULTS: RT-PCR and Western blotting demonstrated decreased expression of SIRT1, SIRT3, SIRT5, and SIRT6 in the NAFLD group in comparison with the control group. Increased expression of lipogenic genes including sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthase (FASN), and acetyl-CoA carboxylase (ACC) was noted within the NAFLD group. In contrast to the other SIRT genes, the expression of SIRT4 was upregulated. CONCLUSION: Our study provides direct evidence of the downregulation of sirtuin signaling that suppresses lipid synthesis in the liver of NAFLD patients, which may promote NAFLD development.
Authors: Julianna D Zeidler; Kelly A Hogan; Guillermo Agorrody; Thais R Peclat; Sonu Kashyap; Karina S Kanamori; Lilian Sales Gomez; Delaram Z Mazdeh; Gina M Warner; Katie L Thompson; Claudia C S Chini; Eduardo Nunes Chini Journal: Am J Physiol Cell Physiol Date: 2022-02-09 Impact factor: 4.249
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