Sep 2008
IRIG: Adipose Tissue - Hometown of insulin resistance
09/10/2008 08:12
It is generally
accepted that accumulation of free fatty
acids (FFA) or its derivatives (such as DAG or Ceramide) contributes to
the pathogenesis of insulin resistance. This may be the molecular basis
of hypothesis of ectopic fat deposition or lipotoxicity. Many studies
suggest that the lipid accumulation is a result of adipose tissue
failure in collection and storage of FFA or triglycerides. If adipose
tissue function is enhanced in this regard, there will be no insulin
resistance. This possibility is supported by the metabolic phenotype of
ob/ob mice with overexpression of adiponectin (see attachment 1, JCI
paper). This line of transgenic mice is more obese than ob/ob mice, but
their insulin sensitivity is as good as that in the lean mice. There is
no chronic inflammation in the adipose tissue of these mice. They are
obese, but healthy.
In contrast, if the adipose tissue function is reduced, insulin
resistance may strike much earlier. This possibility is supported by the
metabolic phenotype of db/db mice with leptin receptor reconstitution in
adipose tissue (see attachment 2, PNAS paper). This line of transgenic
db/db mice is resistant to obesity as adipose tissue can not expand as
needed. However, their insulin resistance is more severe than the native
db/db mice. They are lean, but not healthy as a result of ectopic lipid
overload. It seems that adipose tissue is the hometown of insulin
resistance (=lipids). If the hometown is peaceful and good for living,
insulin resistance will stay there quietly. If the hometown is insulted
by "hurricane" and "curfew", insulin resistance will be subject to
evacuation and make a strike. Insulin may act as a policeman to force
lipids (insulin resistance) back into adipose tissue. If adipose tissue
reaches its limit in expansion without extra room, a high dose of
insulin may have a side effect, such as heart attack. This point is in a
recent review in JAMA (attachment 3).
Have a nice day,
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
acids (FFA) or its derivatives (such as DAG or Ceramide) contributes to
the pathogenesis of insulin resistance. This may be the molecular basis
of hypothesis of ectopic fat deposition or lipotoxicity. Many studies
suggest that the lipid accumulation is a result of adipose tissue
failure in collection and storage of FFA or triglycerides. If adipose
tissue function is enhanced in this regard, there will be no insulin
resistance. This possibility is supported by the metabolic phenotype of
ob/ob mice with overexpression of adiponectin (see attachment 1, JCI
paper). This line of transgenic mice is more obese than ob/ob mice, but
their insulin sensitivity is as good as that in the lean mice. There is
no chronic inflammation in the adipose tissue of these mice. They are
obese, but healthy.
In contrast, if the adipose tissue function is reduced, insulin
resistance may strike much earlier. This possibility is supported by the
metabolic phenotype of db/db mice with leptin receptor reconstitution in
adipose tissue (see attachment 2, PNAS paper). This line of transgenic
db/db mice is resistant to obesity as adipose tissue can not expand as
needed. However, their insulin resistance is more severe than the native
db/db mice. They are lean, but not healthy as a result of ectopic lipid
overload. It seems that adipose tissue is the hometown of insulin
resistance (=lipids). If the hometown is peaceful and good for living,
insulin resistance will stay there quietly. If the hometown is insulted
by "hurricane" and "curfew", insulin resistance will be subject to
evacuation and make a strike. Insulin may act as a policeman to force
lipids (insulin resistance) back into adipose tissue. If adipose tissue
reaches its limit in expansion without extra room, a high dose of
insulin may have a side effect, such as heart attack. This point is in a
recent review in JAMA (attachment 3).
Have a nice day,
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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