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Title: Salicylates promote mitochondrial biogenesis by regulating the expression of PGC-1α in murine 3T3-L1 pre-adipocytes

Abstract

Mitochondrial dysfunction has been associated with insulin resistance and diabetes. Decreased mitochondrial density and mitochondrial copy numbers have been found in insulin-resistant individuals. Restoration of the number of mitochondria and normal mitochondrial function has become an important therapeutic target of diabetes. Salicylate, the main active ingredient in aspirin, has been in medicinal use since ancient times. Little information regarding the effects of salicylate on mitochondrial function has been reported. In this study, we assessed the effects of salicylate on the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) signaling pathway and mitochondrial biogenesis in pre-adipocytes. Our findings demonstrate that treatment with salicylate promoted the expression of PGC-1α and its downstream targets nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM). Importantly, salicylate treatment significantly increased the number of mDNA, citrate synthase activity, expression of respiratory chain complex I, and mitochondrial mass, which were suppressed by the specific AMPK inhibitor Compound C. Indeed, salicylate treatment induced the phosphorylation of AMPK, which was involved in the induction of PGC-1α, NRF1, and TFAM. Importantly, inhibition of PGC-1α expression using PGC-1α small RNA interference abolished the effects of salicylate on mitochondrial biogenesis. These results suggest that salicylate has a potential therapeutic capacity againstmore » mitochondrial dysfunction in diabetes. - Highlights: • First time to show that salicylate promotes the expressions of PGC-1α, NRF1, TFAM. • First time to show that salicylate stimulates mitochondrial biogenesis. • AMPK mediates the effect of salicylate on PGC-1α expression. • Suggesting the roles of salicylate in mitochondrial dysfunction related disease.« less

Authors:
 [1];  [2]; ;  [3];  [4];  [1]
  1. Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei Province (China)
  2. Department of Obstetrics and Gynecology, Xiaogan Central Hospital Affiliated to Wuhan University of Science and Technology, Xiaogan 432000, Hubei Province (China)
  3. Department of Endocrinology, Xiaogan Central Hospital Affiliated to Wuhan University of Science and Technology, Xiaogan, 432000, Hubei Province (China)
  4. Department of Cardiovascular, Xiaogan Central Hospital Affiliated to Wuhan University of Science and Technology, Xiaogan, 432000, Hubei Province (China)
Publication Date:
OSTI Identifier:
22719080
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 491; Journal Issue: 2; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETYLSALICYLIC ACID; BIOLOGICAL RECOVERY; CITRATES; DISEASES; INHIBITION; INSULIN; MITOCHONDRIA; PHOSPHORYLATION; RECEPTORS; RNA; TRANSCRIPTION; TRANSCRIPTION FACTORS

Citation Formats

Yan, Yimin, Yang, Xiaohong, Zhao, Tao, Zou, Yi, Li, Rui, and Xu, Yancheng. Salicylates promote mitochondrial biogenesis by regulating the expression of PGC-1α in murine 3T3-L1 pre-adipocytes. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2017.07.074.
Yan, Yimin, Yang, Xiaohong, Zhao, Tao, Zou, Yi, Li, Rui, & Xu, Yancheng. Salicylates promote mitochondrial biogenesis by regulating the expression of PGC-1α in murine 3T3-L1 pre-adipocytes. United States. doi:10.1016/J.BBRC.2017.07.074.
Yan, Yimin, Yang, Xiaohong, Zhao, Tao, Zou, Yi, Li, Rui, and Xu, Yancheng. Sat . "Salicylates promote mitochondrial biogenesis by regulating the expression of PGC-1α in murine 3T3-L1 pre-adipocytes". United States. doi:10.1016/J.BBRC.2017.07.074.
@article{osti_22719080,
title = {Salicylates promote mitochondrial biogenesis by regulating the expression of PGC-1α in murine 3T3-L1 pre-adipocytes},
author = {Yan, Yimin and Yang, Xiaohong and Zhao, Tao and Zou, Yi and Li, Rui and Xu, Yancheng},
abstractNote = {Mitochondrial dysfunction has been associated with insulin resistance and diabetes. Decreased mitochondrial density and mitochondrial copy numbers have been found in insulin-resistant individuals. Restoration of the number of mitochondria and normal mitochondrial function has become an important therapeutic target of diabetes. Salicylate, the main active ingredient in aspirin, has been in medicinal use since ancient times. Little information regarding the effects of salicylate on mitochondrial function has been reported. In this study, we assessed the effects of salicylate on the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) signaling pathway and mitochondrial biogenesis in pre-adipocytes. Our findings demonstrate that treatment with salicylate promoted the expression of PGC-1α and its downstream targets nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM). Importantly, salicylate treatment significantly increased the number of mDNA, citrate synthase activity, expression of respiratory chain complex I, and mitochondrial mass, which were suppressed by the specific AMPK inhibitor Compound C. Indeed, salicylate treatment induced the phosphorylation of AMPK, which was involved in the induction of PGC-1α, NRF1, and TFAM. Importantly, inhibition of PGC-1α expression using PGC-1α small RNA interference abolished the effects of salicylate on mitochondrial biogenesis. These results suggest that salicylate has a potential therapeutic capacity against mitochondrial dysfunction in diabetes. - Highlights: • First time to show that salicylate promotes the expressions of PGC-1α, NRF1, TFAM. • First time to show that salicylate stimulates mitochondrial biogenesis. • AMPK mediates the effect of salicylate on PGC-1α expression. • Suggesting the roles of salicylate in mitochondrial dysfunction related disease.},
doi = {10.1016/J.BBRC.2017.07.074},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 491,
place = {United States},
year = {2017},
month = {9}
}