Is high fat diet deleterious in metastatic patients?

CD36

10.1038/nature20791

http://www.cell-stress.com/wp-content/uploads/2017/11/2017A-Aznar-Benitah-Cell-Stress-Advanced-Pub.pdf

"CD36+ cells respond to dietary lipids The histological analyses of the few lymph node metastases that grew from CD36-depleted cells presented an intriguing pattern of large swollen cells that were filled with lipid droplets containing non-metabolized lipids (Fig. 2c, d and Extended Data Fig. 4g). These structures were not present in the oral lesions generated by OSCC cells depleted of CD36 (Extended Data Fig. 4h). We therefore hypothesized that CD36+ cells might specifically require lipid metabolism to exert their metastatic potential. In fact, CD36+ CD44bright cells isolated from primary oral orthotopic tumours, but not their CD36+ CD44bright counterparts, expressed numerous genes involved in lymphatic metastasis and lipid metabolism, which overlapped with the dye+ signature (Extended Data Fig. 5a–d and Supplementary Table 2a–c). Second, CD36+ CD44bright cells expressed higher levels of three key enzymes involved in fatty acid β-oxidation (ACADVL, ACADM and HADHA; Extended Data Fig. 5e). Third, depletion of ACSL1, which adds an acyl-coenzyme A moiety to fatty acids to activate their oxidation27,28, significantly reduced the lymph node metastatic penetrance of parental OSCC cells and OSCC cells overexpressing CD36, but not primary tumour uptake (Extended Data Fig. 5f–j). Notably, NSG mice fed with a high-fat diet developed more and larger lymph node metastases, in a CD36-dependent manner (Fig. 3a, Extended Data Fig. 6a and Supplementary Table 3). The boost in metastatic potential of OSCCs in high-fat diet-fed mice correlated with an increase in the percentage of CD36+ cells in oral and metastatic lesions, suggesting that the expression of CD36 might be sensitive to the concentration of fatty acids (Extended Data Fig. 6a). Indeed, the percentage of CD36+ cells was also strongly elevated when OSCC cells were co-cultured with OP9-derived adipocytes, but not with non-adipogenic OP9 parental cells or with squamous cell carcinoma-associated fibroblasts (Extended Data Fig. 6b, c). In addition, exposure of cultured OSCC cells to palmitic acid, a dietary fatty acid recognized by CD36 (ref. 29), for 2 days also robustly increased the percentage of CD36+ cells (Extended Data Fig. 6e). Palmitic acid increased the size and frequency of lymph node metastases in a manner dependent on CD36, without affecting primary tumour growth. Notably, palmitic even promoted lung metastasis in 10% of mice, something we did not observe in the more than 100 mice inoculated with control SCC-25 tumour cells (Fig. 3b). Importantly, OSCC cells expressing mutant CD36 (CD36-K164A) with an impaired ability to internalize lipids30 generated primary lesions with the same penetrance as cells harbouring wild-type CD36, but displayed substantially fewer and much smaller metastases (Fig. 3c and Extended Data Fig. 5f–h). Lymph node metastases generated by CD36-K164A tumour cells contained large lipid droplets similar to those formed after endogenous CD36 depletion (Extended Data Fig. 7a). As CD36 can activate fatty acid β-oxidation31,32, we hypothesized that CD36 inhibition leads to accumulation of endogenously synthesized, unmetabolized lipids. This continuous lipid accumulation would ultimately result in metastatic lipotoxicity and cell death. Indeed, caspase-3 immunoreactivity was observed within and surrounding the lipid droplet-rich areas, both in metastases expressing the CD36-K164A mutant and in those depleted of endogenous CD36 (Extended Data Fig. 7b, c)."
doi:10.1038/nature20791 Targeting metastasis-initiating cells through the fatty acid receptor CD36 Gloria Pascual1 , Alexandra Avgustinova1 , Stefania Mejetta2 , Mercè Martín1 , Andrés Castellanos1 , Camille Stephan-Otto Attolini1 , Antoni Berenguer1 , Neus Prats1 , Agustí Toll3, Juan Antonio Hueto4, Coro Bescós4, Luciano Di Croce2,5,6 & Salvador Aznar Benitah1,5


I have read this paper and my analysis is not that DIETARY palmitic acid enhances the metastatic potential of malignant tumours even in mice.