Breast Cancer Endocrine Therapy Promotes Weight Gain With Distinct Adipose Tissue Effects in Lean and Obese Female Mice.

Autor:	Scalzo RL; Division of Endocrinology, Metabolism & Diabetes, Department of Medicine; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Center for Women's Health Research; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Rocky Mountain Regional VA Medical Center, Aurora, CO 80045, USA., Foright RM; Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA., Hull SE; Division of Endocrinology, Metabolism & Diabetes, Department of Medicine; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Knaub LA; Division of Endocrinology, Metabolism & Diabetes, Department of Medicine; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Johnson-Murguia S; Department of Pathology, University of Oklahoma Health Sciences Center, Stephenson Cancer Center, Harold Hamm Diabetes Research Center, Oklahoma City, OK 73104, USA., Kinanee F; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Kaplan J; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Houck JA; Division of Endocrinology, Metabolism & Diabetes, Department of Medicine; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Johnson G; Division of Endocrinology, Metabolism & Diabetes, Department of Medicine; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Sharp RR; Department of Cell Biology, University of Oklahoma Health Sciences Center, Stephenson Cancer Center, Harold Hamm Diabetes Research Center, Oklahoma City, OK 73104, USA., Gillen AE; Division of Hematology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Jones KL; Department of Cell Biology, University of Oklahoma Health Sciences Center, Stephenson Cancer Center, Harold Hamm Diabetes Research Center, Oklahoma City, OK 73104, USA., Zhang AMY; Diabetes Research Group, Life Sciences Institute, Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada., Johnson JD; Diabetes Research Group, Life Sciences Institute, Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada., MacLean PS; Division of Endocrinology, Metabolism & Diabetes, Department of Medicine; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Center for Women's Health Research; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Reusch JEB; Division of Endocrinology, Metabolism & Diabetes, Department of Medicine; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Center for Women's Health Research; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Rocky Mountain Regional VA Medical Center, Aurora, CO 80045, USA., Wright-Hobart S; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Wellberg EA; Center for Women's Health Research; University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Department of Pathology, University of Oklahoma Health Sciences Center, Stephenson Cancer Center, Harold Hamm Diabetes Research Center, Oklahoma City, OK 73104, USA.
Jazyk:	angličtina
Zdroj:	Endocrinology [Endocrinology] 2021 Nov 01; Vol. 162 (11).
DOI:	10.1210/endocr/bqab174
Abstrakt:	Breast cancer survivors treated with tamoxifen and aromatase inhibitors report weight gain and have an elevated risk of type 2 diabetes, especially if they have obesity. These patient experiences are inconsistent with, preclinical studies using high doses of tamoxifen which reported acute weight loss. We investigated the impact of breast cancer endocrine therapies in a preclinical model of obesity and in a small group of breast adipose tissue samples from women taking tamoxifen to understand the clinical findings. Mature female mice were housed at thermoneutrality and fed either a low-fat/low-sucrose (LFLS) or a high-fat/high-sucrose (HFHS) diet. Consistent with the high expression of Esr1 observed in mesenchymal stem cells from adipose tissue, endocrine therapy was associated with adipose accumulation and more preadipocytes compared with estrogen-treated control mice but resulted in fewer adipocyte progenitors only in the context of HFHS. Analysis of subcutaneous adipose stromal cells revealed diet- and treatment-dependent effects of endocrine therapies on various cell types and genes, illustrating the complexity of adipose tissue estrogen receptor signaling. Breast cancer therapies supported adipocyte hypertrophy and associated with hepatic steatosis, hyperinsulinemia, and glucose intolerance, particularly in obese females. Current tamoxifen use associated with larger breast adipocyte diameter only in women with obesity. Our translational studies suggest that endocrine therapies may disrupt adipocyte progenitors and support adipocyte hypertrophy, potentially leading to ectopic lipid deposition that may be linked to a greater type 2 diabetes risk. Monitoring glucose tolerance and potential interventions that target insulin action should be considered for some women receiving life-saving endocrine therapies for breast cancer. (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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