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Diabetology & Metabolic Syndrome
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Open Access 01-12-2024 | Breast Cancer | Research

Differential effects of leptin on energy metabolism in murine cell models of metastatic triple negative breast cancer

Authors: Chaehyun Yum, Chaylen Andolino, Marjorie Anne Layosa, Michael Coleman, Stephen D. Hursting, Dorothy Teegarden

Published in: Diabetology & Metabolic Syndrome | Issue 1/2024

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Abstract

Background

Leptin, an energy balance regulator secreted by adipocytes, increases metastatic potential of breast cancer cells. The impact on cancer cell metabolism remains unclear given that most studies of leptin and breast cancer cell metabolism utilize supraphysiological glucose concentrations.

Methods

Using two murine models of metastatic triple-negative breast cancer (TNBC) differing in genetic alterations (4T1: p53 and Pik3ca mutations; metM-Wntlung: increased Wnt signaling) and cultured in physiological (5 mM) glucose media, we tested the hypothesis that leptin increases migration of metastatic breast cancer cells through regulation of glucose metabolism.

Results

Our results showed that leptin treatment, compared with vehicle, increased cell migration in each cell line, with decreased leptin receptor (Ob-R) mRNA expression in 4T1, but not metM-Wntlung, cells. AMP-activated protein kinase (AMPK) was activated in 4T1 with leptin treatment but decreased in metM-Wntlung. Leptin decreased fatty acid synthase (Fasn) and carnitine palmitoyltransferase 1a (Cpt1a) mRNA expression in 4T1 cells but increased their expression in metM-Wntlung cells. Fatty acid oxidation was not necessary for leptin-induced migration in either cell line. Leptin increased palmitate synthesis from glucose in metM-Wntlung, but not 4T1 cells. Moreover, although leptin increased glucose transporter 1 (Glut1) mRNA expression in both cell lines and inhibition of glycolysis blocked leptin-induced migration in metM-Wntlung, but not 4T1 cells.

Conclusion

Taken together, these results demonstrate that at physiological glucose concentrations, leptin increases migration of 4T1 and metM-Wntlung cells via shared and distinct effects on energy metabolism, suggesting that the type of TNBC genetic alteration plays a role in differential metabolic regulation of leptin-induced migration.
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Metadata
Title
Differential effects of leptin on energy metabolism in murine cell models of metastatic triple negative breast cancer
Authors
Chaehyun Yum
Chaylen Andolino
Marjorie Anne Layosa
Michael Coleman
Stephen D. Hursting
Dorothy Teegarden
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Diabetology & Metabolic Syndrome / Issue 1/2024
Electronic ISSN: 1758-5996
DOI
https://doi.org/10.1186/s13098-024-01535-1

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