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Corosolic acid inhibits adipose tissue inflammation and ameliorates insulin resistance via AMPK activation in high-fat fed mice.
Phytomedicine. 2016 Feb 15; 23(2):181-90.P

Abstract

BACKGROUND

Adipose tissue inflammation is tightly associated with the development of insulin resistance. Corosolic acid (CRA), a natural triterpenoid, is well known as "phyto-insulin" due to its insulin-like activities. However, its underlying mechanism remains unknown.

PURPOSE

In this study, we investigated the mechanisms of CRA on improving insulin resistance both in vivo and in vitro.

METHODS

C57BL/6 mice were fed with normal diet, high-fat diet (HFD) or HFD with CRA, respectively. General biochemical parameters in blood and glucose intolerance in mice were assayed. Meanwhile, proinflammatory cytokines and macrophage infiltrations in adipose tissues were analyzed by real-time PCR and immunohistochemical staining. The effects of CRA on insulin signaling transduction and AMPK activity in adipose tissues were investigated by western blot. Furthermore, the effects of CRA on AMPK were confirmed on 3T3-L1 cells by using both AMPK inhibitor and AMPKα1/2-specific siRNA RESULTS: CRA attenuated hyperlipidemia, improved insulin sensitivity and glucose intolerance in mice. Meanwhile, it alleviated inflammation in adipose tissues, demonstrated by the suppression of IKKβ phosphorylation and down-regulation of gene expressions of proinflammatory cytokines. Histological analysis revealed that CRA attenuated macrophage infiltrations into adipose tissue. It also improved insulin signaling transduction by modification of Ser/Thr phosphorylation of IRS-1 and downstream Akt, thereby improved insulin sensitivity in HFD-fed mice. Furthermore, CRA regulated AMPK activation in a LKB1-dependent manner. AMPKα knockdown in adipocytes abolished the inhibitory effects of CRA on IKKβ and IRS-1 serine phosphorylation, indicating that CRA inhibited inflammation and ameliorated insulin resistance via AMPK activation.

CONCLUSIONS

CRA inhibited inflammation with improvement in adipose tissue dysfunction and ameliorated insulin resistance in an AMPK-dependent manner.

Authors+Show Affiliations

State Key Laboratory of Natural Medicines, Department of Chinese Medicines Analysis, China Pharmaceutical University, Nanjing 210009, People's Republic of China.State Key Laboratory of Natural Medicines, Department of Chinese Medicines Analysis, China Pharmaceutical University, Nanjing 210009, People's Republic of China.State Key Laboratory of Natural Medicines, Department of Chinese Medicines Analysis, China Pharmaceutical University, Nanjing 210009, People's Republic of China.Shanghai Hua Yu Chinese Herbs Co., Ltd, People's Republic of China.State Key Laboratory of Natural Medicines, Department of Chinese Medicines Analysis, China Pharmaceutical University, Nanjing 210009, People's Republic of China.State Key Laboratory of Natural Medicines, Department of Chinese Medicines Analysis, China Pharmaceutical University, Nanjing 210009, People's Republic of China.State Key Laboratory of Natural Medicines, Department of Chinese Medicines Analysis, China Pharmaceutical University, Nanjing 210009, People's Republic of China. Electronic address: xiaodongwen123@126.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26926180

Citation

Yang, Jie, et al. "Corosolic Acid Inhibits Adipose Tissue Inflammation and Ameliorates Insulin Resistance Via AMPK Activation in High-fat Fed Mice." Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, vol. 23, no. 2, 2016, pp. 181-90.
Yang J, Leng J, Li JJ, et al. Corosolic acid inhibits adipose tissue inflammation and ameliorates insulin resistance via AMPK activation in high-fat fed mice. Phytomedicine. 2016;23(2):181-90.
Yang, J., Leng, J., Li, J. J., Tang, J. F., Li, Y., Liu, B. L., & Wen, X. D. (2016). Corosolic acid inhibits adipose tissue inflammation and ameliorates insulin resistance via AMPK activation in high-fat fed mice. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 23(2), 181-90. https://doi.org/10.1016/j.phymed.2015.12.018
Yang J, et al. Corosolic Acid Inhibits Adipose Tissue Inflammation and Ameliorates Insulin Resistance Via AMPK Activation in High-fat Fed Mice. Phytomedicine. 2016 Feb 15;23(2):181-90. PubMed PMID: 26926180.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Corosolic acid inhibits adipose tissue inflammation and ameliorates insulin resistance via AMPK activation in high-fat fed mice. AU - Yang,Jie, AU - Leng,Jing, AU - Li,Jing-Jing, AU - Tang,Jing-fu, AU - Li,Yi, AU - Liu,Bao-Lin, AU - Wen,Xiao-Dong, Y1 - 2016/01/21/ PY - 2015/08/27/received PY - 2015/12/07/revised PY - 2015/12/15/accepted PY - 2016/3/2/entrez PY - 2016/3/2/pubmed PY - 2016/10/19/medline KW - AMPK KW - Adipose tissue KW - Corosolic acid KW - Inflammation KW - Insulin resistance SP - 181 EP - 90 JF - Phytomedicine : international journal of phytotherapy and phytopharmacology JO - Phytomedicine VL - 23 IS - 2 N2 - BACKGROUND: Adipose tissue inflammation is tightly associated with the development of insulin resistance. Corosolic acid (CRA), a natural triterpenoid, is well known as "phyto-insulin" due to its insulin-like activities. However, its underlying mechanism remains unknown. PURPOSE: In this study, we investigated the mechanisms of CRA on improving insulin resistance both in vivo and in vitro. METHODS: C57BL/6 mice were fed with normal diet, high-fat diet (HFD) or HFD with CRA, respectively. General biochemical parameters in blood and glucose intolerance in mice were assayed. Meanwhile, proinflammatory cytokines and macrophage infiltrations in adipose tissues were analyzed by real-time PCR and immunohistochemical staining. The effects of CRA on insulin signaling transduction and AMPK activity in adipose tissues were investigated by western blot. Furthermore, the effects of CRA on AMPK were confirmed on 3T3-L1 cells by using both AMPK inhibitor and AMPKα1/2-specific siRNA RESULTS: CRA attenuated hyperlipidemia, improved insulin sensitivity and glucose intolerance in mice. Meanwhile, it alleviated inflammation in adipose tissues, demonstrated by the suppression of IKKβ phosphorylation and down-regulation of gene expressions of proinflammatory cytokines. Histological analysis revealed that CRA attenuated macrophage infiltrations into adipose tissue. It also improved insulin signaling transduction by modification of Ser/Thr phosphorylation of IRS-1 and downstream Akt, thereby improved insulin sensitivity in HFD-fed mice. Furthermore, CRA regulated AMPK activation in a LKB1-dependent manner. AMPKα knockdown in adipocytes abolished the inhibitory effects of CRA on IKKβ and IRS-1 serine phosphorylation, indicating that CRA inhibited inflammation and ameliorated insulin resistance via AMPK activation. CONCLUSIONS: CRA inhibited inflammation with improvement in adipose tissue dysfunction and ameliorated insulin resistance in an AMPK-dependent manner. SN - 1618-095X UR - https://www.unboundmedicine.com/medline/citation/26926180/Corosolic_acid_inhibits_adipose_tissue_inflammation_and_ameliorates_insulin_resistance_via_AMPK_activation_in_high_fat_fed_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0944-7113(16)00006-4 DB - PRIME DP - Unbound Medicine ER -