Countries as diverse as England and Ghana are suffering from mass obesity. Food, especially processed food is readily available and becoming quite inexpensive.
A recent note in NEJM by Abate-Shen, details the connection between fat and prostate cancer. This is a compelling presentation of data and well worth following. She notes:
Although most prostate cancers are relatively indolent
and therefore not life-threatening, highly aggressive and metastatic
disease develops in a subgroup of patients, and obesity has been
associated with increased aggressiveness of prostate cancer. Chen et al. analyzed two key tumor-suppressor genes, PTEN and PML,
that protect against prostate cancer. Tumor-suppressor genes promote
cell functions that prevent cancer; therefore, their loss is often
associated with accelerated development of cancer phenotypes. The loss
of both PTEN and PML often occurs in the most aggressive
forms of prostate cancer. Chen et al. investigated the functional
consequences of the loss of PTEN and PML using mice that had been engineered to be deficient in these genes. They found that in mice deficient in Pten in the prostate, locally invasive prostate cancer developed, whereas in 30% of mice lacking both Pten and Pml,
prostate cancer that metastasized to lymph nodes developed. These
findings were interpreted to indicate that these genes work together to
suppress a more aggressive prostate cancer phenotype. ...They found that among the top genes and
biologic pathways affected were those involved in lipid production, a
finding that suggests an association between fat production by the
prostate cancer cells and an aggressive phenotype. In fact, they showed
that the tumors that developed in the mice after the loss of Pten and Pml
had high levels of key lipids in their cells. They also found evidence
that increased lipid production is triggered by activation of the
mitogen-activated protein kinase (MAPK) signaling pathway, which is
frequently deregulated in prostate cancer. These findings led the investigators to consider whether fat may
provide a cell-intrinsic signal to promote aggressive subtypes of
prostate cancer by activating MAPK signaling. To test this idea, they
fed the tumor-prone mice a high-fat diet and investigated whether more
prevalent or more aggressive prostate cancer developed in these mice.
The high-fat diet mimicked the effect of the loss of tumor-suppressor
genes; in particular, the “obese” ... mice had a
greater tendency toward the development of metastases, which occurred
not only in lymph nodes but also in soft tissues such as the lung.
Leveraging these findings, the authors then investigated whether
fatostatin, a small-molecule inhibitor that targets a key regulator of
fat production, could prevent metastasis. Indeed, the mice that were
given fatostatin had less tumor growth and a lower incidence of
metastasis than the control mice. Overall, these findings suggest that
reducing levels of fat in prostate cells may improve outcomes of
prostate cancer.
Yes, fat is a driver, and a powerful one. Just think, many diseases could readily be prevented by just shutting one's mouth!
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