title: Tamoxifen reduces fat mass by boosting reactive oxygen species.
abstract: As the pandemic of obesity is growing, a variety of animal models have been generated to study the mechanisms underlying the increased adiposity and development of metabolic disorders. Tamoxifen (Tam) is widely used to activate Cre recombinase that spatiotemporally controls target gene expression and regulates adiposity in laboratory animals. However, a critical question remains as to whether Tam itself affects adiposity and possibly confounds the functional study of target genes in adipose tissue. Here we administered Tam to Cre-absent forkhead box O1 (FoxO1) floxed mice (f-FoxO1) and insulin receptor substrate Irs1/Irs2 double floxed mice (df-Irs) and found that Tam induced approximately 30% reduction (P<0.05) in fat mass with insignificant change in body weight. Mechanistically, Tam promoted reactive oxygen species (ROS) production, apoptosis and autophagy, which was associated with downregulation of adipogenic regulator peroxisome proliferator-activated receptor gamma and dedifferentiation of mature adipocytes. However, normalization of ROS potently suppressed Tam-induced apoptosis, autophagy and adipocyte dedifferentiation, suggesting that ROS may account, at least in part, for the changes. Importantly, Tam-induced ROS production and fat mass reduction lasted for 4-5 weeks in the f-FoxO1 and df-Irs mice. Our data suggest that Tam reduces fat mass via boosting ROS, thus making a recovery period crucial for posttreatment study.
authors.affiliation: Department of Human Nutrition, Foods and Exercise, Fralin Life Science Institute, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Human Nutrition, Foods and Exercise, Fralin Life Science Institute, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Zou
authors.affiliation: Department of Human Nutrition, Foods and Exercise, Fralin Life Science Institute, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Human Nutrition, Foods and Exercise, Fralin Life Science Institute, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA, USA.
authors.forename: L E
authors.initials: LE
authors.lastname: Linarelli
authors.affiliation: Department of Human Nutrition, Foods and Exercise, Fralin Life Science Institute, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Amarell
authors.affiliation: Department of Human Nutrition, Foods and Exercise, Fralin Life Science Institute, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Passaro
authors.affiliation: Department of Human Nutrition, Foods and Exercise, Fralin Life Science Institute, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Human Nutrition, Foods and Exercise, Fralin Life Science Institute, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Z
authors.identifier: 0000000176159788
authors.initials: Z
authors.lastname: Cheng
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017667:Adipocytes / Q000187:drug effects / Q000473:pathology; D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002452:Cell Count; D015536:Down-Regulation / Q000187:drug effects; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D013629:Tamoxifen; D000111:Acetylcysteine