Ketogenic diet promotes tumor ferroptosis but induces relative corticosterone deficiency that accelerates cachexia

Ferrer, Miriam; Mourikis, Nicholas; Davidson, Emma E.; Kleeman, Sam O.; Zaccaria, Marta; Habel, Jill; Rubino, Rachel; Gao, Qing; Flint, Thomas R.; Young, Lisa R.; Connell, Claire M.; Lukey, Michael J.; Goncalves, Marcus D.; White, Eileen; Venkitaraman, Ashok R.; Janowitz, Tobias

doi:10.1016/j.cmet.2023.05.008

Cited by 30 publications

(16 citation statements)

References 58 publications

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“…Excitingly, the same research group found that applying dexamethasone during KD treatment might delay cachexia onset without affecting the inhibition of tumor growth, providing fundamental insight into reversing the limitations of the clinical application of KD. 156 …”

Section: Targeted Dietary Interventions and Mechanistic Insights Into...mentioning

confidence: 99%

Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential

Xiao,

Gong,

et al. 2024

Sig Transduct Target Ther

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Diet, serving as a vital source of nutrients, exerts a profound influence on human health and disease progression. Recently, dietary interventions have emerged as promising adjunctive treatment strategies not only for cancer but also for neurodegenerative diseases, autoimmune diseases, cardiovascular diseases, and metabolic disorders. These interventions have demonstrated substantial potential in modulating metabolism, disease trajectory, and therapeutic responses. Metabolic reprogramming is a hallmark of malignant progression, and a deeper understanding of this phenomenon in tumors and its effects on immune regulation is a significant challenge that impedes cancer eradication. Dietary intake, as a key environmental factor, can influence tumor metabolism. Emerging evidence indicates that dietary interventions might affect the nutrient availability in tumors, thereby increasing the efficacy of cancer treatments. However, the intricate interplay between dietary interventions and the pathogenesis of cancer and other diseases is complex. Despite encouraging results, the mechanisms underlying diet-based therapeutic strategies remain largely unexplored, often resulting in underutilization in disease management. In this review, we aim to illuminate the potential effects of various dietary interventions, including calorie restriction, fasting-mimicking diet, ketogenic diet, protein restriction diet, high-salt diet, high-fat diet, and high-fiber diet, on cancer and the aforementioned diseases. We explore the multifaceted impacts of these dietary interventions, encompassing their immunomodulatory effects, other biological impacts, and underlying molecular mechanisms. This review offers valuable insights into the potential application of these dietary interventions as adjunctive therapies in disease management.

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Section: Targeted Dietary Interventions and Mechanistic Insights Into...mentioning

confidence: 99%

Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential

Xiao,

Gong,

et al. 2024

Sig Transduct Target Ther

View full text Add to dashboard Cite

show abstract

“…While the ketogenic diet may impede the tumor's growth rate, persistent weight loss may engender cachexia. Recent studies indicate that the utilization of glucocorticoids alongside a ketogenic diet may avert the onset of cachexia and correspondingly elongate survival rates 258 . To date, most of the experiments conducted have only been based on animal models, and further studies are required to determine how the ketogenic diet can be safely applied in clinical anticancer therapy.…”

Section: Prevention and Treatment Of Obesity‐associated Diseasesmentioning

confidence: 99%

Epigenetic modifications in obesity‐associated diseases

Long,

Mao,

Liu

et al. 2024

MedComm

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The global prevalence of obesity has reached epidemic levels, significantly elevating the susceptibility to various cardiometabolic conditions and certain types of cancer. In addition to causing metabolic abnormalities such as insulin resistance (IR), elevated blood glucose and lipids, and ectopic fat deposition, obesity can also damage pancreatic islet cells, endothelial cells, and cardiomyocytes through chronic inflammation, and even promote the development of a microenvironment conducive to cancer initiation. Improper dietary habits and lack of physical exercise are important behavioral factors that increase the risk of obesity, which can affect gene expression through epigenetic modifications. Epigenetic alterations can occur in early stage of obesity, some of which are reversible, while others persist over time and lead to obesity‐related complications. Therefore, the dynamic adjustability of epigenetic modifications can be leveraged to reverse the development of obesity‐associated diseases through behavioral interventions, drugs, and bariatric surgery. This review provides a comprehensive summary of the impact of epigenetic regulation on the initiation and development of obesity‐associated cancers, type 2 diabetes, and cardiovascular diseases, establishing a theoretical basis for prevention, diagnosis, and treatment of these conditions.

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“…Therefore, targeting a novel iGPX4 alternative isoform could alleviate ferroptosis and treat metabolic-associated fatty liver disease. Moreover, in the mouse model of interleukin (IL)-6-associated cancer cachexia, ketogenic diet (KD)-fed mice exhibited delayed tumor growth and shortened survival [ 28 ]. This was attributed to the KD-induced increase in lipid peroxidation and systemic REDOX imbalance, subsequently leading to glutathione system oversaturation, triggering ferroptosis in cancer cells, and ultimately delaying tumor growth.…”

Section: Introductionmentioning

confidence: 99%

Microbial metabolite deoxycholic acid-mediated ferroptosis exacerbates high-fat diet-induced colonic inflammation

Wang,

Chu,

Dong

et al. 2024

Molecular Metabolism

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Ketogenic diet promotes tumor ferroptosis but induces relative corticosterone deficiency that accelerates cachexia

Cited by 30 publications

References 58 publications

Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential

Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential

Epigenetic modifications in obesity‐associated diseases

Microbial metabolite deoxycholic acid-mediated ferroptosis exacerbates high-fat diet-induced colonic inflammation

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