title: Impact of Doxorubicin Treatment on the Physiological Functions of White Adipose Tissue.
abstract: 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.
authors.affiliation: Immunometabolism Research Group, Department of Cellular Biology and Development, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
authors.forename: Luana Amorim
authors.initials: LA
authors.lastname: Biondo
authors.affiliation: Immunometabolism Research Group, Department of Cellular Biology and Development, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
authors.forename: Edson Alves
authors.initials: EA
authors.lastname: Lima Junior
authors.affiliation: Immunometabolism Research Group, Department of Cellular Biology and Development, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
authors.forename: Camila Oliveira
authors.initials: CO
authors.lastname: Souza
authors.affiliation: Department of Biological Sciences, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of Sao Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Maysa Mariana
authors.initials: MM
authors.lastname: Cruz
authors.affiliation: Department of Biological Sciences, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of Sao Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Roberta D C
authors.initials: RD
authors.lastname: Cunha
authors.affiliation: Department of Biological Sciences, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of Sao Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Alonso-Vale
authors.affiliation: Department of Physiology, Physiology of Nutrition Discipline, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Lila Missae
authors.initials: LM
authors.lastname: Oyama
authors.affiliation: Department of Physiology, Physiology of Nutrition Discipline, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Claudia M Oller
authors.initials: CM
authors.lastname: Nascimento
authors.affiliation: Faculty of Nursing and Nutrition, Federal University of Goiás (UFG), Goiânia, GO, Brazil.
authors.forename: Gustavo Duarte
authors.initials: GD
authors.lastname: Pimentel
authors.affiliation: Department of Psychobiology, Universidade Federal de São Paulo-UNIFESP, São Paulo, SP, Brazil.
authors.forename: Ronaldo V T
authors.initials: RV
authors.lastname: Dos Santos
authors.affiliation: Department of Physical Education, State University of São Paulo "Júlio de Mesquita Filho" (UNESP), Presidente Prudente, SP, Brazil.
authors.forename: Fabio Santos
authors.initials: FS
authors.lastname: Lira
authors.affiliation: Immunometabolism Research Group, Department of Cellular Biology and Development, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, SP, Brazil.
authors.forename: José Cesar
authors.initials: JC
authors.lastname: Rosa Neto
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D054392:Adipokines / Q000378:metabolism*; D052242:Adiponectin / Q000096:biosynthesis / Q000235:genetics; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004734:Energy Metabolism / Q000187:drug effects*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D050155:Lipogenesis / Q000235:genetics; D051379:Mice
chemical_list: D054392:Adipokines; D052242:Adiponectin; D007328:Insulin; D004317:Doxorubicin; D055372:AMP-Activated Protein Kinases; D005947:Glucose