• 'Keto' molecule may be useful in prevent

    From ScienceDaily@1:317/3 to All on Wednesday, April 27, 2022 22:30:48
    'Keto' molecule may be useful in preventing and treating colorectal
    cancer, study suggests

    Date:
    April 27, 2022
    Source:
    University of Pennsylvania School of Medicine
    Summary:
    Beta-hydroxybutyrate, an alternative-energy molecule produced by
    the body in response to starvation or low-carb diets, strongly
    suppresses the growth of colorectal tumors in lab experiments,
    according to a new study.



    FULL STORY ==========================================================================
    A molecule produced in the liver in response to low-carb "ketogenic"
    diets has a powerful effect in suppressing colorectal tumor growth and
    may be useful as a preventive and treatment of such cancers, according
    to a new study from researchers at the Perelman School of Medicine at
    the University of Pennsylvania.


    ==========================================================================
    In the study, published in Nature, researchers initially found that
    mice on low-carb, high-fat ketogenic diets have a striking resistance
    to colorectal tumor development and growth. The scientists then traced
    this effect to beta- hydroxybutyrate (BHB), a small organic molecule
    produced in the liver in response to keto diets or starvation.

    "Our findings suggest that this natural molecule, BHB, could someday
    become a standard part of colorectal cancer care and prevention,"
    said study co-senior author Maayan Levy, PhD, an assistant professor of Microbiology at Penn Medicine, whose laboratory collaborated with the lab
    of Christoph Thaiss, PhD, also an assistant professor of Microbiology. The study's first author was Oxana Dmitrieva-Posocco, PhD, a postdoctoral researcher in Levy's lab.

    Colorectal cancer is one of the most common cancer types and kills more
    than 50,000 Americans annually, making it the country's third leading
    cause of cancer mortality. Alcohol use, obesity, red meat, and low-fiber
    and high-sugar diets have all been linked to greater colorectal cancer
    risk.

    In the study, Levy, Thaiss and their teams set out to determine, with experiments in mice, whether different types of diet could inhibit
    colorectal cancer development and growth. They put six groups of mice
    on diets that had varying fat-to-carb ratios, and then used a standard
    chemical technique that normally induces colorectal tumors.

    They found that the two most ketogenic diets, with 90 percent fat-to-carb ratios -- one used lard (pig fat), the other Crisco (mostly soybean oil)
    - - prevented colorectal tumor development in most of the animals on
    those diets.

    By contrast, all the animals on the other diets, including low-fat,
    high-carb diets, developed tumors. Even when the researchers started
    the mice on these diets after colorectal tumors had started growing,
    the diets showed a "treatment effect" by markedly slowing further tumor
    growth and proliferation.



    ==========================================================================
    In subsequent experiments, the scientists determined that this tumor suppression is associated with a slower production, by stem cells,
    of new epithelial cells lining the colon. Ultimately, they traced this
    gut-cell growth slowdown to BHB -- normally produced by the liver as part
    of a "starvation response," and triggered in this case by the low-carb
    keto diets.

    BHB is known to work as an alternative fuel source for key organs in
    low-carb conditions. However, the researchers showed that it is not
    only a fuel source but also a potent growth-slowing signal, at least
    for gut-lining cells. They were able to reproduce the tumor-suppressing
    effects of the keto diets simply by giving the mice BHB, either in
    their water or via an infusion mimicking the liver's natural secretion
    of the molecule.

    The team showed that BHB exerts its gut-cell growth-slowing effect by activating a surface receptor called Hcar2. This in turn stimulates the expression of a growth-slowing gene, Hopx.

    Experiments with gut-lining cells from humans provided evidence that
    BHB has the same growth-slowing effect on these cells, via the human
    versions of Hcar2 and Hopx.Colorectal tumor cells that don't express
    these two genes were not responsive to BHB treatment, suggesting their
    utility as possible predictors of treatment efficiency.

    "Clinical trials of BHB supplementation are needed before any
    recommendation can be made about its use in prevention or treatment,"
    Thaiss said.

    The researchers are now setting up just such a clinical trial of BHB
    -- which is widely available as a dieting supplement -- in colorectal
    cancer patients.

    They are also continuing to study BHB's potential anticancer effects
    in other parts of the body, and are investigating the effects of other molecules produced under ketogenic conditions.

    The study was funded by the National Institutes of Health (R01 CA218133,
    R01 CA227629, P30 CA-006927, DP2AG067511, P30 ES013508, DP2AG067492, P30-DK-050306, P30-AR-069589, P30-DK-019525), the BSF US-Israel
    Foundation, the Searle Scholar program, the Pew Charitable Trust,
    the Edward Mallinckrodt, Jr. Foundation, the Abramson Cancer Center,
    the Borrelli Family, the Global Probiotics Council, the National Mouse Metabolic Phenotyping Centers, the IDSA Foundation, and the Thyssen
    Foundation.


    ========================================================================== Story Source: Materials provided by University_of_Pennsylvania_School_of_Medicine. Note: Content may be
    edited for style and length.


    ========================================================================== Journal Reference:
    1. Oxana Dmitrieva-Posocco, Andrea C. Wong, Patrick Lundgren,
    Aleksandra M.

    Golos, He'le`ne C. Descamps, Lenka Dohnalova', Zvi Cramer, Yuhua
    Tian, Brian Yueh, Onur Eskiocak, Gabor Egervari, Yemin Lan, Jinping
    Liu, Jiaxin Fan, Jihee Kim, Bhoomi Madhu, Kai Markus Schneider,
    Svetlana Khoziainova, Natalia Andreeva, Qiaohong Wang, Ning Li,
    Emma E. Furth, Will Bailis, Judith R. Kelsen, Kathryn E. Hamilton,
    Klaus H. Kaestner, Shelley L.

    Berger, Jonathan A. Epstein, Rajan Jain, Mingyao Li, Semir Beyaz,
    Christopher J. Lengner, Bryson W. Katona, Sergei I. Grivennikov,
    Christoph A. Thaiss, Maayan Levy. b-Hydroxybutyrate suppresses
    colorectal cancer. Nature, 2022; DOI: 10.1038/s41586-022-04649-6 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220427115716.htm

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