@article{59756d4b6753430fac7b02048956adfd,
title = "Diabetes and insulin in regulation of brain cholesterol metabolism",
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.",
author = "Ryo Suzuki and Kevin Lee and Enxuan Jing and Biddinger, {Sudha B.} and McDonald, {Jeffrey G.} and Montine, {Thomas J.} and Suzanne Craft and Kahn, {C. Ronald}",
note = "Funding Information: We thank David Russell (University of Texas Southwestern Medical School) for helpful discussion and the LIPID MAPS Large Scale Collaborative Grant (GM069338) for assay of brain sterols. We also thank Jay Horton and Guosheng Liang for providing SREBP-1 and SREBP-2 antibodies; and Wenyu Jiang and Diane Mathis for providing NOD diabetic mice. We are grateful to M. Rourk and G. Smyth for animal care; C. Cahill (Joslin DERC Advanced Microscopy Core); and A. Clermont, M. Poillucci (DERC Physiology Core), H. Li (DERC Specialized Assay Core), and J. Schroeder (DERC Genomics Core) for technical assistance. This work was supported by NIH grants DK31036, 33210, and 60937 (to C. R. K.), ADRC AG05136 (to S. C.), GM069338 (to J. G. M), and P30 DK036836 (Joslin DERC Core Facilities). R.S. is a recipient of research fellowships from the Manpei Suzuki Diabetes Foundation of Tokyo, Japan, and the Uehara Memorial Foundation, Japan. Copyright: Copyright 2011 Elsevier B.V., All rights reserved.",
year = "2010",
month = dec,
day = "1",
doi = "10.1016/j.cmet.2010.11.006",
language = "English (US)",
volume = "12",
pages = "567--579",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "6",
}