Abstract
The brain is the most cholesterol-rich organ in the body, most of which comes from in situ synthesis. Here we demonstrate that in insulin-deficient diabetic mice, there is a reduction in expression of the major transcriptional regulator of cholesterol metabolism, SREBP-2, and its downstream genes in the hypothalamus and other areas of the brain, leading to a reduction in brain cholesterol synthesis and synaptosomal cholesterol content. These changes are due, at least in part, to direct effects of insulin to regulate these genes in neurons and glial cells and can be corrected by intracerebroventricular injections of insulin. Knockdown of SREBP-2 in cultured neurons causes a decrease in markers of synapse formation and reduction of SREBP-2 in the hypothalamus of mice using shRNA results in increased feeding and weight gain. Thus, insulin and diabetes can alter brain cholesterol metabolism, and this may play an important role in the neurologic and metabolic dysfunction observed in diabetes and other disease states.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 567-579 |
| Number of pages | 13 |
| Journal | Cell Metabolism |
| Volume | 12 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 1 2010 |
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ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
- Physiology
Cite this
Diabetes and insulin in regulation of brain cholesterol metabolism. / Suzuki, Ryo; Lee, Kevin; Jing, Enxuan; Biddinger, Sudha B.; McDonald, Jeffrey G.; Montine, Thomas J.; Craft, Suzanne; Kahn, C. Ronald.
In: Cell Metabolism, Vol. 12, No. 6, 01.12.2010, p. 567-579.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Diabetes and insulin in regulation of brain cholesterol metabolism
AU - Suzuki, Ryo
AU - Lee, Kevin
AU - Jing, Enxuan
AU - Biddinger, Sudha B.
AU - McDonald, Jeffrey G.
AU - Montine, Thomas J.
AU - Craft, Suzanne
AU - Kahn, C. Ronald
PY - 2010/12/1
Y1 - 2010/12/1
N2 - The brain is the most cholesterol-rich organ in the body, most of which comes from in situ synthesis. Here we demonstrate that in insulin-deficient diabetic mice, there is a reduction in expression of the major transcriptional regulator of cholesterol metabolism, SREBP-2, and its downstream genes in the hypothalamus and other areas of the brain, leading to a reduction in brain cholesterol synthesis and synaptosomal cholesterol content. These changes are due, at least in part, to direct effects of insulin to regulate these genes in neurons and glial cells and can be corrected by intracerebroventricular injections of insulin. Knockdown of SREBP-2 in cultured neurons causes a decrease in markers of synapse formation and reduction of SREBP-2 in the hypothalamus of mice using shRNA results in increased feeding and weight gain. Thus, insulin and diabetes can alter brain cholesterol metabolism, and this may play an important role in the neurologic and metabolic dysfunction observed in diabetes and other disease states.
AB - The brain is the most cholesterol-rich organ in the body, most of which comes from in situ synthesis. Here we demonstrate that in insulin-deficient diabetic mice, there is a reduction in expression of the major transcriptional regulator of cholesterol metabolism, SREBP-2, and its downstream genes in the hypothalamus and other areas of the brain, leading to a reduction in brain cholesterol synthesis and synaptosomal cholesterol content. These changes are due, at least in part, to direct effects of insulin to regulate these genes in neurons and glial cells and can be corrected by intracerebroventricular injections of insulin. Knockdown of SREBP-2 in cultured neurons causes a decrease in markers of synapse formation and reduction of SREBP-2 in the hypothalamus of mice using shRNA results in increased feeding and weight gain. Thus, insulin and diabetes can alter brain cholesterol metabolism, and this may play an important role in the neurologic and metabolic dysfunction observed in diabetes and other disease states.
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U2 - 10.1016/j.cmet.2010.11.006
DO - 10.1016/j.cmet.2010.11.006
M3 - Article
VL - 12
SP - 567
EP - 579
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 6
ER -