Manna Linda, Gelsomino Luca, Martino Enrica Antonia, Gentile Massimo, Andò Sebastiano, Bonofiglio Daniela, Giordano Cinzia, Catalano Stefania, Barone Ines
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via P Bucci, 87036, Arcavacata di Rende, CS, Italy.
Azienda Ospedaliera Annunziata, Cosenza, Italy.
Curr Obes Rep. 2025 Jun 5;14(1):52. doi: 10.1007/s13679-025-00644-w.
The global incidence of obesity has risen dramatically in recent decades, with consequent detrimental health effects. Extensive studies have demonstrated that obesity significantly affects the risk, prognosis, and progression of various cancers, including multiple myeloma (MM). As an established modifiable risk factor for both MM and its precursor stages -monoclonal gammopathy of unknown significance (MGUS) and smoldering MM (SMM)- the association between obesity and disease onset has become a compelling area of research. This review presents a comprehensive overview of the current epidemiological evidence linking obesity to MM, emphasizing its role in disease pathogenesis and patient outcomes. It also offers insights into the molecular mechanisms underlying this deleterious association, and discusses therapeutic strategies targeting obesity-driven contributions to MM.
Emerging epidemiological evidence suggests that obesity not only influences MM development but also alters its biological behavior, impacting myelomagenesis, and clinical outcomes. Biologically, multiple pathways exist through which adipose tissue may drive MM onset and progression. Obesity fosters a state of chronic inflammation, where dysfunctional adipocytes and fat-infiltrating immune cells release proinflammatory cytokines, growth factors, adipokines, and fatty acids, contributing to the proliferation and expansion of MM. Additionally, communications between MM cells and adipocytes within the bone marrow are crucial in MM biology. Collectively, the discoveries described in this review underscore the necessity for broader preclinical and clinical investigations to better characterize the complex interplay between obesity and MM, and to determine whether lifestyle interventions can impact MM incidence and clinical outcomes, particularly in high-risk populations.
近几十年来，全球肥胖发病率急剧上升，随之而来的是对健康产生有害影响。大量研究表明，肥胖会显著影响包括多发性骨髓瘤（MM）在内的各种癌症的风险、预后和进展。作为MM及其前驱阶段——意义未明的单克隆丙种球蛋白病（MGUS）和冒烟型MM（SMM）——既定的可改变风险因素，肥胖与疾病发病之间的关联已成为一个引人注目的研究领域。本综述全面概述了将肥胖与MM联系起来的当前流行病学证据，强调其在疾病发病机制和患者预后中的作用。它还深入探讨了这种有害关联背后的分子机制，并讨论了针对肥胖驱动的MM致病因素的治疗策略。
新出现的流行病学证据表明，肥胖不仅影响MM的发生，还会改变其生物学行为，影响骨髓瘤的发生和临床结果。从生物学角度来看，脂肪组织可能通过多种途径驱动MM的发生和进展。肥胖会引发慢性炎症状态，功能失调的脂肪细胞和浸润脂肪的免疫细胞会释放促炎细胞因子、生长因子、脂肪因子和脂肪酸，促进MM的增殖和扩展。此外，骨髓中MM细胞与脂肪细胞之间的相互作用在MM生物学中至关重要。总的来说，本综述中描述的这些发现强调了进行更广泛的临床前和临床研究的必要性，以更好地描述肥胖与MM之间复杂的相互作用，并确定生活方式干预是否会影响MM的发病率和临床结果，特别是在高危人群中。
