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From: ironjustice on 9 Oct 2008 10:06
"Intracellular oxidative stress might accelerate aging by favoring fat
deposition and fat-related disorders"

p66Shc-generated oxidative signal promotes fat accumulation.
Berniakovich I, Trinei M, Stendardo M, Migliaccio E, Minucci S,
Bernardi P, Pelicci PG, Giorgio M
J Biol Chem 2008 Oct 6.

Reactive oxygen species (ROS) and insulin signaling in the adipose
tissue are critical determinants of aging and age-associated
diseases.
It is not clear, however, if they represent independent factors or
they are mechanistically linked.
We investigated the effects of ROS on insulin signaling using, as
model system, the p66Shc-null mice.
P66Shc is a redox enzyme that generates mitochondrial ROS and promotes
aging in mammals.
We report that insulin activates the redox enzyme-activity of p66Shc
specifically in adipocytes, and that p66Shc-generated ROS regulate
insulin signaling through multiple mechanisms, including AKT
phosphorylation, Foxo localization and regulation of selected insulin
target genes.
Deletion of p66Shc resulted in increased mitochondrial uncoupling and
reduced trygliceride accumulation in adipocytes, and, in vivo,
increased metabolic rate, decreased fat mass and resistance to diet-
induced obesity. In addition, p66Shc-/- mice showed impaired thermo-
insulation.
These findings demonstrate that p66Shc-generated ROS regulate the
effect of insulin on the energetic metabolism in mice, and suggest
that intracellular oxidative stress might accelerate aging by favoring
fat deposition and fat-related disorders.

The Journal of biological chemistry [J Biol Chem]
--------------------------------------------------------------------------------

http://www.medwire-news.md/news/service.aspx?k=40&id=39660

Ferritin reveals systemic fat content
07 October 2005
Diabetes Care 2005; 28: 2486-2491


In what they say is a research first, Japanese clinicians have shown
that serum levels of ferritin indicate systemic fat content and
insulin resistance.


Serum ferritin levels, which indicate the level of iron stored in the
body, are known to relate to fasting plasma glucose and insulin
concentrations.


Noting that body fat distribution is also linked with insulin
sensitivity, Tomoyuki Iwasaki (Yokohama City University Graduate
School of Medicine) and team hypothesized that ferritin levels,
adiposity, and insulin sensitivity might all be related.


To test their idea, they used computed tomography to measure visceral
fat area (VFA) and subcutaneous fat area (SFA) in 248 Japanese
individuals, 140 of whom had Type 2 diabetes, and the remainder of
whom were generally healthy.


To eliminate the possibility of the results being affected by the
presence of fatty liver disease, individuals with a history of
abnormally high alcohol intake were excluded from the study.


The scientists then showed that increased serum ferritin
concentrations were significantly correlated with increased VFA, SFA,
and hepatic fat content, as well as insulin sensitivity.


Of note, the authors found a significant relationship between serum
ferritin concentrations and the liver spleen ratio, which measures
hepatic fat content, only in patients with diabetes.


Speculating on the mechanisms behind the links they describe, the
investigators explain: "Increased iron stores in the liver are
postulated to induce liver-mediated insulin resistance, with a reduced
ability of insulin to suppress hepatic glucose production."


"Serum ferritin levels have been reported previously to be associated
with decreased insulin sensitivity and increased fasting plasma
insulin and glucose levels. These abnormalities might lead to
increased adiposity," they continue.


The team therefore concludes: "Measurement of the serum ferritin
concentration may be a highly useful non-invasive and cost-effective
test for the assessment of the fat distribution and degree of insulin
resistance."


Who loves ya.
Tom


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