Oct 2007
IRIG: Obesity without insulin resistance and AMPK crystal
10/15/2007 15:41
There are many hypotheses for insulin resistance
under lipotoxicity. These include inflammation, liver
steatosis, ER stress, oxidative stress, PKC/Ceramide
and hyperinsulinemia. These concepts are generated to
explain pathogenesis of insulin resistance in
obesity. In the current issue of Nature Medicine, a
report suggests that the length of fatty acid chain
is critical for the lipotoxicity. If synthesis of 18C
fatty acid is abolished in the body, the gene
knockout mice will develop obesity on high fat diet
as the wild type mice do. However, insulin
sensitivity will not be severely damaged by the
obesity. The gene is called Elovl6 that catalyze
biosynthesis of 18C fatty acid from 16C fatty acid.
The study suggests that fatty acid with a chain
longer than 16C is “Toxic” (See
attachment 1
and
2).
Elovl6 is similar to SCD1, but SCD1 KO mice are
not obese on HFD. This paper is recommended by Dr.
Eric Ravussin at Pennington.
AMPK is an intracellular sensor of energy (ATP) supply. Activation of MAPK leads to an increase in fat and glucose oxidation in mitochondria in liver and muscle, promotes insulin sensitivity in peripheral tissues, and regulate food intake through the hypothalamus. In “Nature”, the crystal structure of AMPK is reported. The study suggests that in normal condition, AMPK binds to ATP for inactivation (See attachment 3).
By Jianping at PBRC
------------------------------------------------------
Jianping Ye, MD
Professor of Molecular Biology
Pennington Biomedical Research Center
Louisiana State University System
6400 Perkins Road
Baton Rouge, LA 70808
Phone: (225)763-3163
E-mail: yej@pbrc.edu
Webpage: http://labs.pbrc.edu/generegulation/index.htm
AMPK is an intracellular sensor of energy (ATP) supply. Activation of MAPK leads to an increase in fat and glucose oxidation in mitochondria in liver and muscle, promotes insulin sensitivity in peripheral tissues, and regulate food intake through the hypothalamus. In “Nature”, the crystal structure of AMPK is reported. The study suggests that in normal condition, AMPK binds to ATP for inactivation (See attachment 3).
By Jianping at PBRC
------------------------------------------------------
Jianping Ye, MD
Professor of Molecular Biology
Pennington Biomedical Research Center
Louisiana State University System
6400 Perkins Road
Baton Rouge, LA 70808
Phone: (225)763-3163
E-mail: yej@pbrc.edu
Webpage: http://labs.pbrc.edu/generegulation/index.htm
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