Metabolic control Insig(ht)s

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Hi All,

With CR, our cholesterol levels tend to be significant lower than those of ad

libbers. Do our bodies ensure adequate blood cholesterol levels? The below

appears

to detail a new Insi(gh)t into the blood level cholesterol control mechanism.

Editors' Choice: Highlights of the recent literature

Science 19 August 2005: 1155

BIOMEDICINE: Insig(ht)s into Metabolic Control

Cholesterol has received a lot of bad press, but it is essential for human

health.

When we don't get enough cholesterol from our diet, our bodies--specifically our

liver--begin to synthesize it. Conversely, when we eat lots of high- cholesterol

foods, this biosynthetic machinery shuts down. How this feedback regulation

works

has fascinated scientists for over 70 years, and in the past decade,

considerable

progress has been made toward answering that question at the molecular level.

Among the potentially important metabolic regulators identified in studies of

cultured cells are the membrane proteins Insigs-1 and -2, so named because they

are

encoded by insulin-induced genes. The Insigs reside in the endoplasmic

reticulum,

and they appear to act in part by trapping within this compartment a

transcription

factor that is required in the nucleus to turn on the expression of genes

involved

in cholesterol biosynthesis. Engelking et al. show that mice with liver-

specific

deletions of the Insig genes display a severely blunted feedback response; that

is,

they continue making cholesterol even when fed a high-cholesterol diet. These

results establish the physiological significance of the Insigs in a whole-animal

setting and highlight the importance of the liver as the site where the

cholesterol

feedback system operates. -- PAK

The reference for Engelking et al, 2005 is:

Engelking LJ, Liang G, Hammer RE, Takaishi K, Kuriyama H, Evers BM, Li WP,

Horton

JD, Goldstein JL, Brown MS.

Schoenheimer effect explained - feedback regulation of cholesterol synthesis in

mice

mediated by Insig proteins.

J Clin Invest. 2005 Aug 11; [Epub ahead of print]

PMID: 16100574

which is full-text available to all from:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstra\

ct & list_uids=16100574 & query_hl=18

Al Pater, PhD; email: old542000@...

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