Elevated serum β-hydroxybutyrate, a circulating ketone metabolite, accelerates colorectal cancer proliferation and metastasis via ACAT1

Mao, Tianxiao; Qin, Fujian; Zhang, Mengdi; Li, Jing; Li, Jiankang; Lai, Maode

doi:10.1038/s41388-023-02700-y

Cited by 15 publications

(6 citation statements)

References 50 publications

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“…The anticancer properties of the ketone body β-HB have been reported in several instances 3,4 , however, we observed the absence of a KD-induced anticancer effect in the absence of robust gut microbial changes, despite confirmed induction of ketosis in these mice. Thus, ketosis alone seems to be insufficient to ensure CRC suppression, similarly to other studies showing no KD benefits in the context of cancer, despite the induction of ketosis 3,22 .…”

Section: Discussionsupporting

confidence: 66%

The gut microbiome-linked long chain fatty acid stearate suppresses colorectal cancer

Tsenkova,

Brauer,

Pozdeev

et al. 2023

Preprint

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Colorectal cancer (CRC) patients have been shown to possess an altered gut microbiome. Diet is a known microbiome modulator. An attenuating effect of the ketogenic diet (KD) on CRC cell growth has been previously observed, however the role of the gut microbiome in driving this effect remains unknown. Here, we describe a reduced colonic tumor burden upon KD consumption in a CRC mouse model with a humanized microbiome. Importantly, we demonstrate a causal relationship through microbiome transplantation into germ-free mice, whereby alterations in gut microbial function were maintained in the absence of continued selective pressure from the KD. Stearic acid is identified as a putative microbiome-derived anti-cancer metabolite. Taken together, the beneficial effects of the KD are mediated by the gut microbiome and may be dependent on a pre-existing “non-responder” or “responder” gut microbiome profile. These results have important implications for future clinical trials evaluating the effects of the ketogenic diet on human CRC.

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Section: Discussionsupporting

confidence: 66%

The gut microbiome-linked long chain fatty acid stearate suppresses colorectal cancer

Tsenkova,

Brauer,

Pozdeev

et al. 2023

Preprint

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“…Bioinformatic analysis identified the prognostic significance of ACAT1 in ccRCC, with patients exhibiting high ACAT1 expression levels demonstrating a more favorable prognosis than those with low ACAT1 expression. The complex biological processes governing tumor cell invasion and metastasis were emphasized, highlighting the crucial role of the equilibrium between cell proliferation and apoptosis in tumor development [ [19] , [20] ].…”

Section: Discussionmentioning

confidence: 99%

ACAT1 suppresses clear cell renal cell carcinoma progression by AMPK mediated fatty acid metabolism

Zheng,

Zhang,

Zhou

et al. 2024

Translational Oncology

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“…An unhealthy lifestyle such as fatigue, drinking a lot of alcohol, and eating foods high in fat and fat may lead to an increase in 3-hydroxybutyric acid . At the same time, Mao found that the level of 3-hydroxybutyrate was elevated in patients with colorectal cancer. The use of n-3 polyunsaturated fatty acids in dietary interventions is being evaluated for the prevention or treatment of other types of cancer, including breast, skin, and lymphoma .…”

Section: Discussionmentioning

confidence: 99%

Metabolites, Healthy Lifestyle, and Polygenic Risk Score Associated with Upper Gastrointestinal Cancer: Findings from the UK Biobank Study

Li,

Che,

et al. 2024

J. Proteome Res.

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Previous metabolomics studies have highlighted the predictive value of metabolites on upper gastrointestinal (UGI) cancer, while most of them ignored the potential effects of lifestyle and genetic risk on plasma metabolites. This study aimed to evaluate the role of lifestyle and genetic risk in the metabolic mechanism of UGI cancer. Differential metabolites of UGI cancer were identified using partial least-squares discriminant analysis and the Wilcoxon test. Then, we calculated the healthy lifestyle index (HLI) score and polygenic risk score (PRS) and divided them into three groups, respectively. A total of 15 metabolites were identified as UGI-cancer-related differential metabolites. The metabolite model (AUC = 0.699) exhibited superior discrimination ability compared to those of the HLI model (AUC = 0.615) and the PRS model (AUC = 0.593). Moreover, subgroup analysis revealed that the metabolite model showed higher discrimination ability for individuals with unhealthy lifestyles compared to that with healthy individuals (AUC = 0.783 vs 0.684). Furthermore, in the genetic risk subgroup analysis, individuals with a genetic predisposition to UGI cancer exhibited the best discriminative performance in the metabolite model (AUC = 0.770). These findings demonstrated the clinical significance of metabolic biomarkers in UGI cancer discrimination, especially in individuals with unhealthy lifestyles and a high genetic risk.

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Elevated serum β-hydroxybutyrate, a circulating ketone metabolite, accelerates colorectal cancer proliferation and metastasis via ACAT1

Cited by 15 publications

References 50 publications

The gut microbiome-linked long chain fatty acid stearate suppresses colorectal cancer

The gut microbiome-linked long chain fatty acid stearate suppresses colorectal cancer

ACAT1 suppresses clear cell renal cell carcinoma progression by AMPK mediated fatty acid metabolism

Metabolites, Healthy Lifestyle, and Polygenic Risk Score Associated with Upper Gastrointestinal Cancer: Findings from the UK Biobank Study

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