Re: Researchers discover how a high-fat diet causes type 2 diabetes

On Tue, 19 Sep 2006 15:16:36 -0400, William Wagner
<not-to-here-williamwag@xxxxxxxxx> wrote:

In article <4naoaoF9h42qU1@xxxxxxxxxxxxxx>,
"Juhana Harju" <spamshantigiriorama.removespam@xxxxxxxxx> wrote:

William Wagner wrote:
: In article <4nah2nF9h5q0U1@xxxxxxxxxxxxxx>,
: "Juhana Harju" <spamshantigiriorama.removespam@xxxxxxxxx> wrote:
:: Peabody wrote:
::: Juhana Harju says...
:::
:::::: For sometime diabetes has been described as a disorder
:::::: of fat metabolism. This affects beta cells and leads
:::::: in time to high glucose levels for those with the
:::::: genetic disposition. What we consider as classic
:::::: symptoms of diabetes are several steps down the chain
:::::: of causes. Using large population studies high intake
:::::: of saturated fats is related to the risk of diabetes
:::::: and the metabolic syndrome with the level of insulin
:::::: resistance being a common theme. This study looks at
:::::: this origin of the fat handling disorder:
:::
:::::: http://www.NewsTarget.com/020449.html
:::
::::: I'm so confused!
:::
::::: Bill
:::
:::: This might clarify the issue a bit.
:::
:::: http://www.juvenon.com/jhj/vol5no01.htm
:::
::: No, it doesn't. At least not for me.
:::
::: The original article referred to a "high-fat diet", but the
::: Juvenon "explanation" refers to obesity, as being the bad
::: guy. They are not the same thing.
::
:: I guess you did not read the full text. Quote from the site: "There
:: are two toxic effects, one from high glucose, or glycotoxicity, and
:: the other from high fat (lipid), or lipotoxicity."
::
::: I guess I need to read the study itself.
:::
::: I also didn't know that "for sometime diabetes has been
::: described as a disorder of fat metabolism". Who knew?
::: Well, it just seems to me that there is a lot of really
::: fuzzy, conflicting language and thinking in both of these
::: explanations. Need to find the study, I guess.
:::
::: Rats!
:
: What is lipotoxicity ? My dictionary fails me ;))
:
: Glycotoxicity same question perhaps Finland has different ways of
: expressing this.
:
: Bill

I did not invent the words! ;-) As I understand it, those words describe two
pathways which can both induce type 2 diabetes. Lipotoxicity refers to
adverse effects fatty acids can have on tissues and glycotoxicity refers to
adverse effects high blood glucose can have.

http://tinyurl.com/m5zbv

Interesting in that it does not show up in various dictionaries.

Weird

Thanks again Juhana !

"Insight into these mechanisms may contribute to the development of
more effective therapies for common human disorders in which
lipotoxicity contributes to pathogenesis."

I guess this is still in limbo. Small steps for mankind comes to
mind. Perhaps best practice is...............


.................

Lipotoxicity: when tissues overeat.

Schaffer JE.

Department of Internal Medicine, Washington University School of
Medicine, St Louis, Missouri, USA. jschaff@xxxxxxxxxxxx

PURPOSE OF REVIEW: This review will provide the reader with an update on
our understanding of the adverse effects of fatty acid accumulation in
non-adipose tissues, a phenomenon known as lipotoxicity. Recent studies
will be reviewed. Cellular mechanisms involved in the lipotoxic response
will be discussed. Physiologic responses to lipid overload and
therapeutic approaches to decreasing lipid accumulation will be
discussed, as they add to our understanding of important
pathophysiologic mechanisms. RECENT FINDINGS: Excess lipid accumulation
in non-adipose tissues may arise in the setting of high plasma free
fatty acids or triglycerides. Alternatively, lipid overload results from
mismatch between free fatty acid import and utilization. Evidence from
human studies and animal models suggests that lipid accumulation in the
heart, skeletal muscle, pancreas, liver, and kidney play an important
role in the pathogenesis of heart failure, obesity and diabetes. Excess
free fatty acids may impair normal cell signaling, causing cellular
dysfunction. In some circumstances, excess free fatty acids induce
apoptotic cell death. SUMMARY: Recent studies provide clues regarding
the cellular mechanisms that determine whether excess lipid accumulation
is well tolerated or cytotoxic. Critical in this process are physiologic
mechanisms for directing excess free fatty acids to specific tissues as
well as cellular mechanisms for channeling excess fatty acid to
particular metabolic fates. Insight into these mechanisms may contribute
to the development of more effective therapies for common human
disorders in which lipotoxicity contributes to pathogenesis.

Publication Types:
? Review

PMID: 12840659 [PubMed - indexed for MEDLINE]

When I fed lipotoxicity to google, the first hit was

Sivitz WI.
Lipotoxicity and glucotoxicity in type 2 diabetes. Effects on
development and progression.
Postgrad Med. 2001 Apr;109(4):55-9, 63-4. Review.
PMID: 11317469 [PubMed - indexed for MEDLINE]
<http://www.postgradmed.com/issues/2001/04_01/sivitz.htm>

It seems to define lipotoxicity as the diabetogenic effect of
increased circulating free fatty acids or increased cellular fat
content. The excess circulating free fatty acids seem mostly arise
from obesity. A few citations:

"Lipotoxicity is the diabetogenic effect of increased circulating
free fatty acids or increased cellular fat content. This condition
is manifest in several tissues, most notably the liver, muscle,
and pancreatic islet

[...]

It also is thought that excess fuel in the form of fat may be
responsible for raising blood glucose concentrations to those seen
in diabetes. The association between diabetes and obesity is well
established.

[...]

The prevalence of obesity among diabetic patients and observations
that plasma levels of free fatty acids are elevated in most obese
persons suggest that free fatty acids themselves might induce
hyperglycemia."


Other related articles:

Diabetes & Free Fatty Acids, on MedicineNet.com
<http://www.medicinenet.com/script/main/art.asp?articlekey=52045>>

Koutsari C, Jensen MD.
Thematic review series: patient-oriented research. Free fatty acid
metabolism in human obesity.
J Lipid Res. 2006 Aug;47(8):1643-50. Epub 2006 May 9.
PMID: 16685078 [PubMed - in process]
<http://www.jlr.org/cgi/content/short/R600011-JLR200v1> (abstract)
<http://www.jlr.org/cgi/reprint/R600011-JLR200v1> (full text PDF)


--
Matti Narkia
.