Impact of Doxorubicin Treatment on the Physiological Functions of White Adipose Tissue

• Published in: PloS one Vol. 11; no. 3; p. e0151548
• Main Authors: Biondo, Luana Amorim, Lima Junior, Edson Alves, Souza, Camila Oliveira, Cruz, Maysa Mariana, Cunha, Roberta D C, Alonso-Vale, Maria Isabel, Oyama, Lila Missae, Nascimento, Claudia M Oller, Pimentel, Gustavo Duarte, Dos Santos, Ronaldo V T, Lira, Fabio Santos, Rosa Neto, José Cesar
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25-03-2016; Public Library of Science (PLoS)
• Subjects: 3T3-L1 Cells; Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; Adipokines - metabolism; Adiponectin; Adiponectin - biosynthesis; Adiponectin - genetics; Adipose tissue; Adipose Tissue, White - drug effects; Adipose Tissue, White - metabolism; AMP; AMP-activated protein kinase; AMP-Activated Protein Kinases - biosynthesis; AMP-Activated Protein Kinases - genetics; Analysis; Animals; Binding sites; Biology and Life Sciences; Body fat; Breast cancer; Cancer; Cardiac muscle; Cellular biology; Chemotherapy; Diabetes; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Energy balance; Energy Metabolism - drug effects; Environmental science; Fatty acids; Fibroblasts; Gene Expression; Gene Expression Regulation - drug effects; Glucose; Glucose - metabolism; Glucose kinase; Glucose transporter; Heart diseases; Homeostasis; Humans; In vivo methods and tests; Inhibition; Insulin - genetics; Insulin - metabolism; Insulin resistance; Lipase; Lipogenesis; Lipogenesis - genetics; Lipolysis; Liver; Medicine and Health Sciences; Metabolism; Mice; Muscles; Nutrition; Peroxisome proliferator-activated receptors; Pharmaceuticals; Phosphorylation; Physical Sciences; Physiological aspects; Physiology; Quality of life; Secretion; Side effects; Skeletal muscle; Tissues; Transcription factors; Transporter; Triacylglycerol lipase; California; Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0151548

White adipose tissue (WAT) plays a fundamental role in maintaining energy balance and important endocrine functions. The loss of WAT modifies adipokine secretion and disrupts homeostasis, potentially leading to severe metabolic effects and a reduced quality of life. Doxorubicin is a chemotherapeutic agent used clinically because of its good effectiveness against various types of cancer. However, doxorubicin has deleterious effects in many healthy tissues, including WAT, liver, and skeletal and cardiac muscles. Our objective was to investigate the effects of doxorubicin on white adipocytes through in vivo and in vitro experiments. Doxorubicin reduced the uptake of glucose by retroperitoneal adipocytes and 3T3-L1 cells via the inhibition of AMP-activated protein kinase Thr172 phosphorylation and glucose transporter 4 content. Doxorubicin also reduced the serum level of adiponectin and, to a greater extent, the expression of genes encoding lipogenic (Fas and Acc) and adipogenic factors (Pparg, C/ebpa, and Srebp1c) in retroperitoneal adipose tissue. In addition, doxorubicin inhibited both lipogenesis and lipolysis and reduced the hormone-sensitive lipase and adipose tissue triacylglycerol lipase protein levels. Therefore, our results demonstrate the impact of doxorubicin on WAT. These results are important to understand some side effects observed in patients receiving chemotherapy and should encourage new adjuvant treatments that aim to inhibit these side effects.