Calorie restriction outperforms bariatric surgery in a murine model of obesity and triple-negative breast cancer

Kristina Camp; Michael F. Coleman; Tori McFarlane; Steven S. Doerstling; Subreen A. Khatib; Erika T. Rezeli; Alfor G. Lewis; Alexander J. Pfeil; Laura A. Smith; Laura W. Bowers; Farnaz Fouladi; Weida Gong; Elaine M. Glenny; Joel S. Parker; Ginger L. Milne; Ian M. Carroll; Anthony A. Fodor; Randy J. Seeley; Stephen D. Hursting

doi:10.1172/jci.insight.172868

¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

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¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

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¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

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¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

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¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

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¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

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¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

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¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

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¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

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¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

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¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

Find articles by Fouladi, F. in: JCI | PubMed | Google Scholar

¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

Find articles by Gong, W. in: JCI | PubMed | Google Scholar

¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

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¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

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¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

Find articles by Milne, G. in: JCI | PubMed | Google Scholar |

¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

Find articles by Carroll, I. in: JCI | PubMed | Google Scholar

¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

Find articles by Fodor, A. in: JCI | PubMed | Google Scholar

¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

Find articles by Seeley, R. in: JCI | PubMed | Google Scholar |

¹Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Surgery, The University of Michigan, Ann Arbor, United States of America

³College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, United States of America

⁴Lineberger Comprehensive Cancer center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁵Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁶Department of Pharmacology, Vanderbilt University, Nashville, United States of America

Find articles by Hursting, S. in: JCI | PubMed | Google Scholar |

JCI Insight. https://doi.org/10.1172/jci.insight.172868.
Copyright © 2023, Camp et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Published September 12, 2023 - Version history

Obesity promotes triple-negative breast cancer (TNBC), and effective interventions are urgently needed to break the obesity-TNBC link. Epidemiologic studies indicate that bariatric surgery reduces TNBC risk, while evidence is limited or conflicted for weight loss via low-fat diet (LFD) or calorie restriction (CR). Using a murine model of obesity-driven TNBC, we compared the antitumor effects of vertical sleeve gastrectomy (VSG) with LFD, chronic CR, and intermittent CR. Each intervention generated weight and fat loss and suppressed tumor growth relative to obese mice (greatest suppression with CR). VSG and CR regimens exerted both similar and unique effects, as assessed using multi-omic approaches, in reversing obesity-associated transcriptional, epigenetic, secretome, and microbiota changes and restoring antitumor immunity. Thus, in a murine model of TNBC, bariatric surgery and CR each reverse obesity-driven tumor growth via shared and distinct antitumor mechanisms, and CR is superior to VSG in reversing obesity’s procancer effects.

Calorie restriction outperforms bariatric surgery in a murine model of obesity and triple-negative breast cancer

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Calorie restriction outperforms bariatric surgery in a murine model of obesity and triple-negative breast cancer

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