Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
JCI Insight. 2023 Sep 12;8(19):e172868. doi: 10.1172/jci.insight.172868.
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.
肥胖症促进三阴性乳腺癌（TNBC）的发生，迫切需要有效的干预措施来打破肥胖与 TNBC 之间的联系。流行病学研究表明，减重手术可降低 TNBC 的风险，而通过低脂饮食（LFD）或热量限制（CR）减轻体重的证据有限或存在争议。本研究使用肥胖驱动的 TNBC 小鼠模型，比较了垂直袖状胃切除术（VSG）与 LFD、慢性 CR 和间歇性 CR 的抗肿瘤效果。与肥胖小鼠相比，每种干预措施均能减轻体重和体脂，并抑制肿瘤生长（CR 的抑制作用最大）。通过多组学方法评估发现，VSG 和 CR 方案在逆转肥胖相关的转录组、表观遗传学、分泌组和微生物组变化以及恢复抗肿瘤免疫方面发挥了相似和独特的作用。因此，在 TNBC 的小鼠模型中，减重手术和 CR 通过共同和独特的抗肿瘤机制逆转肥胖驱动的肿瘤生长，并且 CR 在逆转肥胖的促癌作用方面优于 VSG。
