Switch to fat harm

[Guest guest]

Hi All,

The below is a review of a pdf-unavailable paper

on a molecular switch than seems to be responsible

for the risk from fats.

This JAMA review is not in Medline yet for the

citation and probably has no Medline abstract, as

in:

1: Hampton T.

Antiangiogenic therapy a two-trick pony?

JAMA. 2005 Mar 2;293(9):1051. No abstract available.

PMID: 15741519 [PubMed - indexed for MEDLINE]

2: Hampton T.

Genetic variant boosts fertility: inverted region of DNA gives

reproductive

edge.

JAMA. 2005 Mar 2;293(9):1050. No abstract available.

PMID: 15741518 [PubMed - indexed for MEDLINE]

Molecular Switch Triggers Fats' Harm

Hampton

It was of possible interest that:

'the investigators do not foresee the research as a means to

helping people freely indulge in fatty foods.

" That's obviously not our goal, " Spiegleman said. " We're not

devoting our professional lives to the freedom of burgers. " '

Hampton T.

JAMA. 2005;293:1180.

Figure: Scientists are gaining insights into how foods rich in

saturated and trans-fats trigger a rise in blood cholesterol and

triglycerides. (Photo credit: Ted Grudzinski/AMA)

Most people know consuming fatty foods can have negative health

effects. Now, researchers studying rats and mice have identified the

molecular mechanism by which saturated and trans-fats trigger a rise

in blood cholesterol and triglycerides, increasing the risk of

cardiovascular disease (Lin et al. Cell. 2005;120:261-273).

The molecular players in this scenario are also found in humans.

Although it remains to be seen whether the results will have clinical

relevance, pharmaceutical companies have already expressed interest

in the implications of the new findings for treating individuals with

elevated blood cholesterol levels.

The researchers, Bruce Spiegelman, PhD, and colleagues at the Dana-

Farber Cancer Institute, in Boston, found that saturated and trans-

fats in the diet induce a molecule called PPAR-coactivator-1, or PGC-

1, to set into action certain biochemical signals in the liver. These

signals result in the production of very low-density lipoprotein

cholesterol, the precursor of the low-density lipoprotein cholesterol

that is secreted into the bloodstream.

Spiegelman and his team came across these findings after they

discovered the family of PGC-1 coactivators (Puigserver et al. Cell.

1998;92:829-839). " It's something we bumped into, " he said. They

found that PGC-1 turned on the genes of lipogenesis in the

liver. " But then when we looked at the lipid levels, they were

actually down in the liver. "

Ultimately, the researchers solved this mystery by revealing that

PGC-1 was performing two functions simultaneously. " It's turning on

the genes of lipogenesis while it's turning on the genes of

transport, " Spiegelman explained. As a result, the newly produced

lipid proteins made in the liver are pumped out into the bloodstream.

PGC-1 produces the first of these effects by binding to members of

a protein family called sterol-responsive element binding proteins

(SREBPs), which go on to stimulate lipogenesis. PGC-1 also promotes

pumping lipoprotein out of the liver by activating a receptor in

liver cells that is known to play a role in hepatic lipid transport.

The researchers now plan to see what happens when the effects of

PGC-1 are hindered, either by blocking the production of PGC-1 itself

or by blocking PGC-1's interaction with SREBP. They also hope to

reveal the molecular mechanism whereby fat induces PGC-1.

Spiegelman's main goal is to understand the broad implications and

physiology of this pathway. " In the metabolic syndrome, or syndrome

X, people have speculated . . . that hepatic lipogenesis may be a

central feature, may be even causal, in other aspects of the

syndrome, " he said. Technologies such as RNA interference should

enable the researchers to suppress this pathway and look at its

consequences in syndrome X. " So I'm pretty excited about that, " he

added.

Even if these efforts provide clues to syndrome X or other

conditions, the investigators do not foresee the research as a means

to helping people freely indulge in fatty foods.

" That's obviously not our goal, " Spiegleman said. " We're not

devoting our professional lives to the freedom of burgers. "

The Cell paper is:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=15680331

=

http://tinyurl.com/4xu45

Al Pater