Direct delivery of leptin to the hypothalamus using recombinant adeno-associated virus vectors results in increased therapeutic efficacy
Lundberg, Cecilia LU
; Jungles, Steven J.
and Mulligan, Richard C.
(2001)
In Nature Biotechnology
19(2).
p.169-172
- Abstract
- The hormone leptin has been shown to be an afferent signal in a negative-feedback loop regulating body weight, and consequently, the administration of the gene product for the treatment of obesity has recently attracted considerable attention. Leptin is produced by adipocytes in response to increased trigyceride storage, and appears to affect body weight primarily through target cells in the hypothalamus. Although plasma levels of leptin correlate positively with adipose tissue mass in normal humans and animals, recent studies have shown that obese humans and animals appear to be relatively resistant to the increased plasma levels of leptin. Analysis of the levels of leptin in the cerebrospinal fluid suggests that the uptake of leptin... (More)
- The hormone leptin has been shown to be an afferent signal in a negative-feedback loop regulating body weight, and consequently, the administration of the gene product for the treatment of obesity has recently attracted considerable attention. Leptin is produced by adipocytes in response to increased trigyceride storage, and appears to affect body weight primarily through target cells in the hypothalamus. Although plasma levels of leptin correlate positively with adipose tissue mass in normal humans and animals, recent studies have shown that obese humans and animals appear to be relatively resistant to the increased plasma levels of leptin. Analysis of the levels of leptin in the cerebrospinal fluid suggests that the uptake of leptin across the blood-brain barrier may be saturable. Taken together, these results suggest that therapeutic approaches to deliver leptin through the circulation may prove to be problematic. Although recent clinical trials have suggested that peripherally administered leptin might lead to a reduction in body weight in humans, it is likely that the more effective delivery of leptin to cellular targets within the central nervous system will be necessary in order to fully reveal the therapeutic potential of the gene product. In an effort to provide a means for the delivery of leptin that obviates the need for the gene product to traverse the blood-brain barrier, we have evaluated the use of recombinant adeno-associated vectors to deliver leptin intraventricularly or directly to the hypothalamus. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1121229
- author
- Lundberg, Cecilia
LU
; Jungles, Steven J.
and Mulligan, Richard C.
- organization
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Biotechnology
- volume
- 19
- issue
- 2
- pages
- 169 - 172
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:11175734
- scopus:0035122529
- ISSN
- 1546-1696
- DOI
- 10.1038/84448
- language
- English
- LU publication?
- yes
- id
- 17f315ab-1928-44b8-8969-085ea2bd17c1 (old id 1121229)
- date added to LUP
- 2016-04-01 16:24:57
- date last changed
- 2022-02-05 08:05:10
@article{17f315ab-1928-44b8-8969-085ea2bd17c1,
abstract = {{The hormone leptin has been shown to be an afferent signal in a negative-feedback loop regulating body weight, and consequently, the administration of the gene product for the treatment of obesity has recently attracted considerable attention. Leptin is produced by adipocytes in response to increased trigyceride storage, and appears to affect body weight primarily through target cells in the hypothalamus. Although plasma levels of leptin correlate positively with adipose tissue mass in normal humans and animals, recent studies have shown that obese humans and animals appear to be relatively resistant to the increased plasma levels of leptin. Analysis of the levels of leptin in the cerebrospinal fluid suggests that the uptake of leptin across the blood-brain barrier may be saturable. Taken together, these results suggest that therapeutic approaches to deliver leptin through the circulation may prove to be problematic. Although recent clinical trials have suggested that peripherally administered leptin might lead to a reduction in body weight in humans, it is likely that the more effective delivery of leptin to cellular targets within the central nervous system will be necessary in order to fully reveal the therapeutic potential of the gene product. In an effort to provide a means for the delivery of leptin that obviates the need for the gene product to traverse the blood-brain barrier, we have evaluated the use of recombinant adeno-associated vectors to deliver leptin intraventricularly or directly to the hypothalamus.}},
author = {{Lundberg, Cecilia and Jungles, Steven J. and Mulligan, Richard C.}},
issn = {{1546-1696}},
language = {{eng}},
number = {{2}},
pages = {{169--172}},
publisher = {{Nature Publishing Group}},
series = {{Nature Biotechnology}},
title = {{Direct delivery of leptin to the hypothalamus using recombinant adeno-associated virus vectors results in increased therapeutic efficacy}},
url = {{http://dx.doi.org/10.1038/84448}},
doi = {{10.1038/84448}},
volume = {{19}},
year = {{2001}},
}