Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression. / Pouladi, Mahmoud A; Xie, Yuanyun; Skotte, Niels Henning; Ehrnhoefer, Dagmar E; Graham, Rona K; Kim, Jeong Eun; Bissada, Nagat; Yang, X William; Paganetti, Paolo; Friedlander, Robert M; Leavitt, Blair R; Hayden, Michael R.

In: Human Molecular Genetics, Vol. 19, No. 8, 15.04.2010, p. 1528-38.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Pouladi, MA, Xie, Y, Skotte, NH, Ehrnhoefer, DE, Graham, RK, Kim, JE, Bissada, N, Yang, XW, Paganetti, P, Friedlander, RM, Leavitt, BR & Hayden, MR 2010, 'Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression', Human Molecular Genetics, vol. 19, no. 8, pp. 1528-38. https://doi.org/10.1093/hmg/ddq026

APA

Pouladi, M. A., Xie, Y., Skotte, N. H., Ehrnhoefer, D. E., Graham, R. K., Kim, J. E., Bissada, N., Yang, X. W., Paganetti, P., Friedlander, R. M., Leavitt, B. R., & Hayden, M. R. (2010). Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression. Human Molecular Genetics, 19(8), 1528-38. https://doi.org/10.1093/hmg/ddq026

Vancouver

Pouladi MA, Xie Y, Skotte NH, Ehrnhoefer DE, Graham RK, Kim JE et al. Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression. Human Molecular Genetics. 2010 Apr 15;19(8):1528-38. https://doi.org/10.1093/hmg/ddq026

Author

Pouladi, Mahmoud A ; Xie, Yuanyun ; Skotte, Niels Henning ; Ehrnhoefer, Dagmar E ; Graham, Rona K ; Kim, Jeong Eun ; Bissada, Nagat ; Yang, X William ; Paganetti, Paolo ; Friedlander, Robert M ; Leavitt, Blair R ; Hayden, Michael R. / Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression. In: Human Molecular Genetics. 2010 ; Vol. 19, No. 8. pp. 1528-38.

Bibtex

@article{2f630886adf54e66a5519748b454846d,
title = "Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression",
abstract = "Levels of full-length huntingtin (FL htt) influence organ and body weight, independent of polyglutamine length. The growth hormone-insulin like growth factor-1 (GH-IGF-1) axis is well established as a regulator of organ growth and body weight. In this study, we investigate the involvement of the IGF-1 pathway in mediating the effect of htt on body weight. IGF-1 expression was examined in transgenic mouse lines expressing different levels of FL wild-type (WT) htt (YAC18 mice), FL mutant htt (YAC128 and BACHD mice) and truncated mutant htt (shortstop mice). We demonstrate that htt influences body weight by modulating the IGF-1 pathway. Plasma IGF-1 levels correlate with body weight and htt levels in the transgenic YAC mice expressing human htt. The effect of htt on IGF-1 expression is independent of CAG size. No effect on body weight is observed in transgenic YAC mice expressing a truncated N-terminal htt fragment (shortstop), indicating that FL htt is required for the modulation of IGF-1 expression. Treatment with 17beta-estradiol (17beta-ED) lowers the levels of circulating IGF-1 in mammals. Treatment of YAC128 with 17beta-ED, but not placebo, reduces plasma IGF-1 levels and decreases the body weight of YAC128 animals to WT levels. Furthermore, given the ubiquitous expression of IGF-1 within the central nervous system, we also examined the impact of FL htt levels on IGF-1 expression in different regions of the brain, including the striatum, cerebellum of YAC18, YAC128 and littermate WT mice. We demonstrate that the levels of FL htt influence IGF-1 expression in striatal tissues. Our data identify a novel function for FL htt in influencing IGF-1 expression.",
keywords = "Animals, Body Weight, Brain, Disease Models, Animal, Gene Expression, Humans, Huntington Disease, Insulin-Like Growth Factor I, Male, Mice, Mice, Transgenic, Nerve Tissue Proteins, Nuclear Proteins, Signal Transduction",
author = "Pouladi, {Mahmoud A} and Yuanyun Xie and Skotte, {Niels Henning} and Ehrnhoefer, {Dagmar E} and Graham, {Rona K} and Kim, {Jeong Eun} and Nagat Bissada and Yang, {X William} and Paolo Paganetti and Friedlander, {Robert M} and Leavitt, {Blair R} and Hayden, {Michael R}",
year = "2010",
month = apr,
day = "15",
doi = "10.1093/hmg/ddq026",
language = "English",
volume = "19",
pages = "1528--38",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "8",

}

RIS

TY - JOUR

T1 - Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression

AU - Pouladi, Mahmoud A

AU - Xie, Yuanyun

AU - Skotte, Niels Henning

AU - Ehrnhoefer, Dagmar E

AU - Graham, Rona K

AU - Kim, Jeong Eun

AU - Bissada, Nagat

AU - Yang, X William

AU - Paganetti, Paolo

AU - Friedlander, Robert M

AU - Leavitt, Blair R

AU - Hayden, Michael R

PY - 2010/4/15

Y1 - 2010/4/15

N2 - Levels of full-length huntingtin (FL htt) influence organ and body weight, independent of polyglutamine length. The growth hormone-insulin like growth factor-1 (GH-IGF-1) axis is well established as a regulator of organ growth and body weight. In this study, we investigate the involvement of the IGF-1 pathway in mediating the effect of htt on body weight. IGF-1 expression was examined in transgenic mouse lines expressing different levels of FL wild-type (WT) htt (YAC18 mice), FL mutant htt (YAC128 and BACHD mice) and truncated mutant htt (shortstop mice). We demonstrate that htt influences body weight by modulating the IGF-1 pathway. Plasma IGF-1 levels correlate with body weight and htt levels in the transgenic YAC mice expressing human htt. The effect of htt on IGF-1 expression is independent of CAG size. No effect on body weight is observed in transgenic YAC mice expressing a truncated N-terminal htt fragment (shortstop), indicating that FL htt is required for the modulation of IGF-1 expression. Treatment with 17beta-estradiol (17beta-ED) lowers the levels of circulating IGF-1 in mammals. Treatment of YAC128 with 17beta-ED, but not placebo, reduces plasma IGF-1 levels and decreases the body weight of YAC128 animals to WT levels. Furthermore, given the ubiquitous expression of IGF-1 within the central nervous system, we also examined the impact of FL htt levels on IGF-1 expression in different regions of the brain, including the striatum, cerebellum of YAC18, YAC128 and littermate WT mice. We demonstrate that the levels of FL htt influence IGF-1 expression in striatal tissues. Our data identify a novel function for FL htt in influencing IGF-1 expression.

AB - Levels of full-length huntingtin (FL htt) influence organ and body weight, independent of polyglutamine length. The growth hormone-insulin like growth factor-1 (GH-IGF-1) axis is well established as a regulator of organ growth and body weight. In this study, we investigate the involvement of the IGF-1 pathway in mediating the effect of htt on body weight. IGF-1 expression was examined in transgenic mouse lines expressing different levels of FL wild-type (WT) htt (YAC18 mice), FL mutant htt (YAC128 and BACHD mice) and truncated mutant htt (shortstop mice). We demonstrate that htt influences body weight by modulating the IGF-1 pathway. Plasma IGF-1 levels correlate with body weight and htt levels in the transgenic YAC mice expressing human htt. The effect of htt on IGF-1 expression is independent of CAG size. No effect on body weight is observed in transgenic YAC mice expressing a truncated N-terminal htt fragment (shortstop), indicating that FL htt is required for the modulation of IGF-1 expression. Treatment with 17beta-estradiol (17beta-ED) lowers the levels of circulating IGF-1 in mammals. Treatment of YAC128 with 17beta-ED, but not placebo, reduces plasma IGF-1 levels and decreases the body weight of YAC128 animals to WT levels. Furthermore, given the ubiquitous expression of IGF-1 within the central nervous system, we also examined the impact of FL htt levels on IGF-1 expression in different regions of the brain, including the striatum, cerebellum of YAC18, YAC128 and littermate WT mice. We demonstrate that the levels of FL htt influence IGF-1 expression in striatal tissues. Our data identify a novel function for FL htt in influencing IGF-1 expression.

KW - Animals

KW - Body Weight

KW - Brain

KW - Disease Models, Animal

KW - Gene Expression

KW - Humans

KW - Huntington Disease

KW - Insulin-Like Growth Factor I

KW - Male

KW - Mice

KW - Mice, Transgenic

KW - Nerve Tissue Proteins

KW - Nuclear Proteins

KW - Signal Transduction

U2 - 10.1093/hmg/ddq026

DO - 10.1093/hmg/ddq026

M3 - Journal article

C2 - 20097678

VL - 19

SP - 1528

EP - 1538

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 8

ER -

ID: 153451393