Qing Shu1,2, Li Chen3,2, Song Wu3,2, Jia Li3,2, Jianmin Liu3,2, Ling Xiao2,4, Rui Chen5, Fengxia Liang6,7. 1. Department of Rehabilitation, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China. 2. Hubei Provincial Collaborative Innovation Center of Preventive Treatment by Acupuncture and Moxibustion, Wuhan, China. 3. College of Acupuncture, Moxibustion and Orthopedics, Hubei University of Chinese Medicine, Wuhan, China. 4. School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, China. 5. Department of Traditional Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 6. College of Acupuncture, Moxibustion and Orthopedics, Hubei University of Chinese Medicine, Wuhan, China, fxliang5@hotmail.com. 7. Hubei Provincial Collaborative Innovation Center of Preventive Treatment by Acupuncture and Moxibustion, Wuhan, China, fxliang5@hotmail.com.
Abstract
OBJECTIVE: To investigate the anorexigenic and anti-obesity effectiveness of electroacupuncture (EA) on high-fat-diet-induced (HFDI) obese rats with insulin resistance (IR) and to reveal the possible mechanisms of EA affecting SIRT1 (silent mating type information regulation 2 homolog 1) in the central nervous system (CNS). METHODS: We divided 60 rats into 6 groups. All interventions, including EA and intracerebroventricular administration, were performed after 8 weeks of model establishment. We tested obesity phenotypes like body weight (BW) gain; food intake; and IR levels including glucose infusion rate, intraperitoneal insulin tolerance test (IPITT), and intraperitoneal glucose tolerance test (IPGTT) during treatment. We detected protein expression and microscopic locations in hypothalamic SIRT1, the transcription factor FOXO1 (forkhead box protein O1), acetylated FOXO1 (Ac-FOXO1), pro-opiomelanocortin (POMC), and neuropeptide Y (NPY) via Western blotting and immunofluorescence, and monitored gene expression by real-time polymerase chain reaction. RESULTS: Like the SIRT1 agonist, EA suppressed BW gain and IR levels in obese rats, but this was only partially blocked by the SIRT1 antagonist. EA could upregulate protein expression of hypothalamic SIRT1 and downregulate the acetylation level of FOXO1 in the hypothalamic arcuate nucleus (ARC), which decreased gene expression of NPY and increased that of POMC. The agonist targeted the hypothalamic SIRT1 gene, unlike EA, which targeted posttranscriptional regulation. CONCLUSION: EA could improve obesity in HFDI rats with IR via its anorectic effect. This effect targeted posttranscriptional regulation of the SIRT1 gene, which induced upregulation of ARC FOXO1 deacetylation and mediated the gene expression of POMC and NPY.
OBJECTIVE: To investigate the anorexigenic and anti-obesity effectiveness of electroacupuncture (EA) on high-fat-diet-induced (HFDI) obeserats with insulin resistance (IR) and to reveal the possible mechanisms of EA affecting SIRT1 (silent mating type information regulation 2 homolog 1) in the central nervous system (CNS). METHODS: We divided 60 rats into 6 groups. All interventions, including EA and intracerebroventricular administration, were performed after 8 weeks of model establishment. We tested obesity phenotypes like body weight (BW) gain; food intake; and IR levels including glucose infusion rate, intraperitoneal insulin tolerance test (IPITT), and intraperitoneal glucose tolerance test (IPGTT) during treatment. We detected protein expression and microscopic locations in hypothalamicSIRT1, the transcription factor FOXO1 (forkhead box protein O1), acetylated FOXO1 (Ac-FOXO1), pro-opiomelanocortin (POMC), and neuropeptide Y (NPY) via Western blotting and immunofluorescence, and monitored gene expression by real-time polymerase chain reaction. RESULTS: Like the SIRT1 agonist, EA suppressed BW gain and IR levels in obeserats, but this was only partially blocked by the SIRT1 antagonist. EA could upregulate protein expression of hypothalamicSIRT1 and downregulate the acetylation level of FOXO1 in the hypothalamic arcuate nucleus (ARC), which decreased gene expression of NPY and increased that of POMC. The agonist targeted the hypothalamicSIRT1 gene, unlike EA, which targeted posttranscriptional regulation. CONCLUSION: EA could improve obesity in HFDI rats with IR via its anorectic effect. This effect targeted posttranscriptional regulation of the SIRT1 gene, which induced upregulation of ARC FOXO1 deacetylation and mediated the gene expression of POMC and NPY.
Authors: Anna Benrick; Milana Kokosar; Min Hu; Martin Larsson; Manuel Maliqueo; Rodrigo Rodrigues Marcondes; Marzia Soligo; Virginia Protto; Elisabet Jerlhag; Antonina Sazonova; Carl Johan Behre; Kurt Højlund; Peter Thorén; Elisabet Stener-Victorin Journal: FASEB J Date: 2017-04-12 Impact factor: 5.191