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Elevated lipolysis in adipose tissue by doxorubicin via PPARα activation associated with hepatic steatosis and insulin resistance.
Eur J Pharmacol 2019; 843:162-176EJ

Abstract

Adipose dysfunction is tightly associated with hepatic insulin resistance and steatosis condition. Doxorubicin would disturb the lipid metabolism both in adipose and liver. Here we projected that doxorubicin would impede lipogenesis and elevated lipolysis in adipose tissue would elevate the circulatory lipid profile and leads to insulin resistance. Further exacerbated lipid profile in circulation would impair the lipid metabolism in hepatic tissue which leads to fatty liver condition and consequently related disease during doxorubicin treatment. Doxorubicin impairs the lipogenesis through PPARγ and augments lipolysis and fatty acid oxidation through ATGL and PPARα in adipose tissue. Increased fatty acid level by adipose tissue in circulation would translocate into the liver and dysregulates AHR, PXR, PPARγ, ATGL and Apo B,which further develop insulin resistance and hepatic steatosis condition. The findings add to the mechanistic role of association between adipose tissue dysfunction and hepatic dysfunction.

Authors+Show Affiliations

Department of Biomedical Sciences, School of Biosciences and Technology, VIT, Vellore, Tamil Nadu 632014, India.Department of Biomedical Sciences, School of Biosciences and Technology, VIT, Vellore, Tamil Nadu 632014, India.Department of Biomedical Sciences, School of Biosciences and Technology, VIT, Vellore, Tamil Nadu 632014, India.Department of Biomedical Sciences, School of Biosciences and Technology, VIT, Vellore, Tamil Nadu 632014, India.Jubilee Centre for Medical Research, Jubilee Mission Medical College and Research Institute, Thrissur, Kerala, India.Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu 620024, India.Department of Oncology, Lombardi Comprehensive Cancer Center (LCCC), Georgetown University Medical Center (GUMC), E504, NRB, 3970 Reservoir Rd. NW, Washington, D.C., USA.Department of Biomedical Sciences, School of Biosciences and Technology, VIT, Vellore, Tamil Nadu 632014, India. Electronic address: abilash.vg@vit.ac.in.Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil 626126, Tamil Nadu, India. Electronic address: sankarganesh@klu.ac.in.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30452912

Citation

Renu, Kaviyarasi, et al. "Elevated Lipolysis in Adipose Tissue By Doxorubicin Via PPARα Activation Associated With Hepatic Steatosis and Insulin Resistance." European Journal of Pharmacology, vol. 843, 2019, pp. 162-176.
Renu K, K B S, Parthiban S, et al. Elevated lipolysis in adipose tissue by doxorubicin via PPARα activation associated with hepatic steatosis and insulin resistance. Eur J Pharmacol. 2019;843:162-176.
Renu, K., K B, S., Parthiban, S., S, S., George, A., P B, T. P., ... Arunachalam, S. (2019). Elevated lipolysis in adipose tissue by doxorubicin via PPARα activation associated with hepatic steatosis and insulin resistance. European Journal of Pharmacology, 843, pp. 162-176. doi:10.1016/j.ejphar.2018.11.018.
Renu K, et al. Elevated Lipolysis in Adipose Tissue By Doxorubicin Via PPARα Activation Associated With Hepatic Steatosis and Insulin Resistance. Eur J Pharmacol. 2019 Jan 15;843:162-176. PubMed PMID: 30452912.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Elevated lipolysis in adipose tissue by doxorubicin via PPARα activation associated with hepatic steatosis and insulin resistance. AU - Renu,Kaviyarasi, AU - K B,Sruthy, AU - Parthiban,Sujitha, AU - S,Sugunapriyadharshini, AU - George,Alex, AU - P B,Tirupathi Pichiah, AU - Suman,Shubhankar, AU - V G,Abilash, AU - Arunachalam,Sankarganesh, Y1 - 2018/11/16/ PY - 2018/06/12/received PY - 2018/11/09/revised PY - 2018/11/14/accepted PY - 2018/11/20/pubmed PY - 2019/4/16/medline PY - 2018/11/20/entrez KW - Adipose tissue dysfunction KW - Doxorubicin KW - Fatty liver KW - Hepatic steatosis KW - Insulin resistance KW - PPARα SP - 162 EP - 176 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 843 N2 - Adipose dysfunction is tightly associated with hepatic insulin resistance and steatosis condition. Doxorubicin would disturb the lipid metabolism both in adipose and liver. Here we projected that doxorubicin would impede lipogenesis and elevated lipolysis in adipose tissue would elevate the circulatory lipid profile and leads to insulin resistance. Further exacerbated lipid profile in circulation would impair the lipid metabolism in hepatic tissue which leads to fatty liver condition and consequently related disease during doxorubicin treatment. Doxorubicin impairs the lipogenesis through PPARγ and augments lipolysis and fatty acid oxidation through ATGL and PPARα in adipose tissue. Increased fatty acid level by adipose tissue in circulation would translocate into the liver and dysregulates AHR, PXR, PPARγ, ATGL and Apo B,which further develop insulin resistance and hepatic steatosis condition. The findings add to the mechanistic role of association between adipose tissue dysfunction and hepatic dysfunction. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/30452912/Elevated_lipolysis_in_adipose_tissue_by_doxorubicin_via_PPARα_activation_associated_with_hepatic_steatosis_and_insulin_resistance L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(18)30673-3 DB - PRIME DP - Unbound Medicine ER -