Kofi 2012-02-25 22:44:56
PLoS One. 2010 Sep 30;5(9)
Decreased fat storage by Lactobacillus paracasei is associated with
increased levels of angiopoietin-like 4 protein (ANGPTL4).
Aronsson L, Huang Y, Parini P, Korach-Andre M, Hakansson J, Gustafsson
JA, Pettersson S, Arulampalam V, Rafter J.
Department of Microbiology, Cell and Tumor Biology, Karolinska
Institutet, Stockholm, Sweden.
BACKGROUND: Intervention strategies for obesity are global issues that
require immediate attention. One approach is to exploit the growing
consensus that beneficial gut microbiota could be of use in intervention
regimes. Our objective was to determine the mechanism by which the
probiotic bacteria Lactobacillus paracasei ssp paracasei F19 (F19) could
alter fat storage. Angiopoietin-like 4 (ANGPTL4) is a circulating
lipoprotein lipase (LPL) inhibitor that controls triglyceride deposition
into adipocytes and has been reported to be regulated by gut microbes.
METHODOLOGY/PRINCIPAL FINDINGS: A diet intervention study of mice fed
high-fat chow supplemented with F19 was carried out to study potential
mechanistic effects on fat storage. Mice given F19 displayed
significantly less body fat, as assessed by magnetic resonance imaging,
and a changed lipoprotein profile. Given that previous studies on fat
storage have identified ANGPTL4 as an effector, we also investigated
circulating levels of ANGPTL4, which proved to be higher in the
F19-treated group. This increase, together with total body fat and
triglyceride levels told a story of inhibited LPL action through ANGPTL4
leading to decreased fat storage. Co-culture experiments of colonic cell
lines and F19 were set up in order to monitor any ensuing alterations in
ANGPTL4 expression by qPCR. We observed that potentially secreted
factors from F19 can induce ANGPTL4 gene expression, acting in part
through the peroxisome proliferator activated receptors alpha and gamma.
To prove validity of in vitro findings, germ-free mice were
monocolonized with F19. Here we again found changes in serum
triglycerides as well as ANGPTL4 in response to F19.
CONCLUSIONS/SIGNIFICANCE: Our results provide an interesting mechanism
whereby modifying ANGPTL4, a central player in fat storage regulation,
through manipulating gut flora could be an important gateway upon which
intervention trials of weight management can be based.
* Research Support, Non-U.S. Gov’t