Abstract
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 multiomics approaches, in reversing obesity-associated transcript, epigenetics, 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.
Authors
Kristina K. Camp, Michael F. Coleman, Tori L. 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
Figure 3
Epigenetic regulation through DNA methylation of mammary adipose tissue reveals transcriptional mediators of the gene expression profile conserved between human and mouse adipose tissue following surgical but not dietary weight loss.
