I liked the headline for the email.

Evidently, obesity modifies or distorts some functions of fat cells that
can even lead to cell death. Among other things, this "obesity stress"
can activate proteins that cause insulin resistance. Some chemicals
appear to alleviate the condition - in mice. There are hints that some
(unidentified) diabetic drugs work to prevent this cellular damage.

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Source:      American Society for Biochemistry and Molecular Biology
Date:     August 30, 2007
   
Understanding How Obese Fat Cells Work

Science Daily — In obese individuals, fat cells are bloated and inflamed
because they receive too many nutrients, including lipids. In these
cells, various components cannot work properly anymore and, instead,
they activate new proteins to cope with the situation. One of the most
challenged organelles in obese fat cells is a maze-like compartment
called the endoplasmic reticulum (ER) that makes proteins and lipid
droplets and senses the amount of nutrients that enter the cell.

Margaret F. Gregor and Gokhan S. Hotamisligil review current knowledge
about how the ER works in fat cells and is modified in obesity. They
show that when a fat cell receives too many nutrients, the ER is
overwhelmed and triggers a process called the unfolded protein response
(UPR). This process is one of many cellular responses that activate
proteins that increase inflammation and can even result in the death of
the cell. UPR also causes insulin resistance, a condition in which the
production and function of insulin -- a hormone produced by the pancreas
-- is impaired and blood sugar is too high.

The scientists show that by better understanding how the ER works, it
may be possible to devise a therapy that enhances the function of the ER
and maybe improve the health of obese people. Already, two molecules
that protect the ER from obesity-related stress have shown some success
in mice. Called PBA and TUDCA, the molecules decreased blood sugar and
insulin levels and improved overall response to insulin production.

ER stress may also be reduced by targeting molecules involved in the UPR
process. For example, a drug called Salubrinal was recently shown to
inhibit one of the UPR-involved molecules and to protect cells from ER
stress-induced cell death. Also, there is emerging evidence that
anti-diabetic drugs may also work, at least in part, through this mechanism.

A deeper knowledge of how fat cells become dysfunctional will be
critical in devising successful therapies in the future, the scientists
conclude.

Article: "Adipocyte stress: the endoplasmic reticulum and metabolic
disease," by Margaret F. Gregor and Gokhan S. Hotamisligil

Note: This story has been adapted from a news release issued by American
Society for Biochemistry and Molecular Biology.