Obesity, visceral adiposity, and prostate cancer: What is the role of lifestyle interventions?

Shirazipour, Celina H.; Freedland, Stephen J.

doi:10.1002/cncr.32165

Cited by 2 publications

(3 citation statements)

References 21 publications

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“…Prostate cancer represents the second cause of cancer-related death in men in the US and the third in Europe ( 10, 11 ). Although AR signaling is the major driver of the disease, evidence is accumulating that obesity and high consumption of saturated FAs contribute to the development of more advanced and lethal prostate cancer ( 12, 13, 42, 58 ). This is particularly worrisome in Western countries where prostate cancer incidence is rising and both obesity and consumption of unhealthy diets are increasing at alarming rates.…”

Section: Discussionmentioning

confidence: 99%

“…Prostate cancer is the second cause of cancer-related death in men in the United States, and the third in Europe ( 10, 11 ). Obesity status, lifestyle, and environmental factors, including diet, profoundly affect the course of the disease ( 12 ). Although the association between obesity and worse prostate cancer progression/lethality is well established ( 13 ), the link between increased consumption of saturated fatty acids (FA) and fatal prostate cancer is still the object of debate ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

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Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer

Boufaied,

Chetta,

Hallal

et al. 2024

Cancer Research

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Cancer cells exhibit metabolic plasticity to meet oncogene-driven dependencies while coping with nutrient availability. A better understanding of how systemic metabolism impacts the accumulation of metabolites that reprogram the tumor microenvironment (TME) and drive cancer could facilitate development of precision nutrition approaches. Using the Hi-MYC prostate cancer mouse model, we demonstrated that an obesogenic high-fat diet (HFD) rich in saturated fats accelerates the development of c-MYC–driven invasive prostate cancer through metabolic rewiring. Although c-MYC modulated key metabolic pathways, interaction with an obesogenic HFD was necessary to induce glycolysis and lactate accumulation in tumors. These metabolic changes were associated with augmented infiltration of CD206+ and PD-L1+ tumor-associated macrophages (TAM) and FOXP3+ regulatory T cells, as well as with the activation of transcriptional programs linked to disease progression and therapy resistance. Lactate itself also stimulated neoangiogenesis and prostate cancer cell migration, which were significantly reduced following treatment with the lactate dehydrogenase inhibitor FX11. In patients with prostate cancer, high saturated fat intake and increased body mass index were associated with tumor glycolytic features that promote the infiltration of M2-like TAMs. Finally, upregulation of lactate dehydrogenase, indicative of a lactagenic phenotype, was associated with a shorter time to biochemical recurrence in independent clinical cohorts. This work identifies cooperation between genetic drivers and systemic metabolism to hijack the TME and promote prostate cancer progression through oncometabolite accumulation. This sets the stage for the assessment of lactate as a prognostic biomarker and supports strategies of dietary intervention and direct lactagenesis blockade in treating advanced prostate cancer. Significance: Lactate accumulation driven by high-fat diet and MYC reprograms the tumor microenvironment and promotes prostate cancer progression, supporting the potential of lactate as a biomarker and therapeutic target in prostate cancer. See related commentary by Frigo, p. 1742

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer

Boufaied,

Chetta,

Hallal

et al. 2024

Cancer Research

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“… 28 Number of recent studies reported that VO is more reliable clinical marker for predicting outcome than traditional view on obesity defined by BMI. 29 , 30 , 31 , 32 , 33 The useful predictor of VO is visceral-to-subcutaneous adipose tissue area ratio (VSR), and high VSR is associated with poor oncologic outcome. 34 , 35 , 36 , 37 Also, another body composition abnormality, the new concept of sarcopenic obesity (SO), a combination of excess adiposity and sarcopenia, seems to have powerful negative prognostic impact in oncology treatment and is gaining increased attention in cancer research.…”

Section: Introductionmentioning

confidence: 99%

Influence of nutritional status and body composition on postoperative events and outcome in patients treated for primary localized retroperitoneal sarcoma

Ramanovic,

Novak,

Perhavec

et al. 2024

Radiology and Oncology

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Background Retroperitoneal sarcomas (RPS) are rare tumours of mesenchymal origin, commonly presented as a large tumour mass at time of diagnosis. We investigated the impact of body composition on outcome in patients operated on for primary localized RPS. Patients and methods We retrospectively analysed data for all patients operated on for primary RPS at our institution between 1999 and 2020. Preoperative skeletal muscle area (SMA), visceral and subcutaneous adipose tissue area (VAT and SAT) and muscle radiation attenuation (MRA) were calculated using computed tomography scans at the level of third lumbar vertebra. European Working Group on Sarcopenia in Older People (EWGSOP2) criteria were applied to define myopenia. Using maximum log-rank statistic method we determined the optimal cut-off values of body composition parameters. Myosteatosis was defined based on determined MRA cut-offs. Results In total 58 patient were eligible for the study. With a median follow-up of 116 months, the estimated 5-year overall survival (OS) and local-recurrence free survival (LRFS) were 66.8% and 77.6%, respectively. Patients with myopenia had significantly lower 5-year OS compared to non-myopenic (p = 0.009). Skeletal muscle index and subcutaneous adipose tissue index predicted LRFS on univariate analysis (p = 0.052 and p = 0.039, respectively). In multivariate analysis high visceral-to-subcutaneous adipose tissue area ratio (VSR) independently predicted higher postoperative complication rate (89.2% vs. 10.8%, p = 0.008). Myosteatosis was associated with higher postoperative morbidity. Conclusions Myopenia affected survival, but not postoperative outcome in RPS. Visceral obesity, VSR (> 0.26) and myosteatosis were associated with higher postoperative morbidity. VSR was better prognostic factor than VAT in RPS.

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Obesity, visceral adiposity, and prostate cancer: What is the role of lifestyle interventions?

Abstract: The findings from Dickerman et al's research highlight the need to consider and implement lifestyle interventions to target weight loss and the risk of prostate cancer. Interventions that combine 2 lifestyle behaviors, diet and exercise, may be most impactful.

Cited by 2 publications

References 21 publications

Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer

Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer

Influence of nutritional status and body composition on postoperative events and outcome in patients treated for primary localized retroperitoneal sarcoma

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