Hypothalamic ΔFosB prevents age-related metabolic decline and functions via SNS

DSpace/Manakin Repository

Hypothalamic ΔFosB prevents age-related metabolic decline and functions via SNS

Citable link to this page


Title: Hypothalamic ΔFosB prevents age-related metabolic decline and functions via SNS
Author: Sato, Kazusa; Idelevich, Anna; Nagano, Kenichi; Rowe, Glenn C.; Gori, Francesca; Baron, Roland

Note: Order does not necessarily reflect citation order of authors.

Citation: Sato, Kazusa, Anna Idelevich, Kenichi Nagano, Glenn C. Rowe, Francesca Gori, and Roland Baron. 2017. “Hypothalamic ΔFosB prevents age-related metabolic decline and functions via SNS.” Aging (Albany NY) 9 (2): 353-369. doi:10.18632/aging.101157. http://dx.doi.org/10.18632/aging.101157.
Full Text & Related Files:
Abstract: The ventral hypothalamus (VHT) integrates several physiological cues to maintain glucose homeostasis and energy balance. Aging is associated with increased glucose intolerance but the underlying mechanisms responsible for age-related metabolic decline, including neuronal signaling in the VHT, remain elusive. We have shown that mice with VHT-targeted overexpression of ΔFosB, a splice variant of the AP1 transcription factor FosB, exhibit increased energy expenditure, leading to decreased adiposity. Here, we show that VHT-targeted overexpression of ΔFosB also improves glucose tolerance, increases insulin sensitivity in target organs and thereby suppresses insulin secretion. These effects are also observed by the overexpression of dominant negative JunD, demonstrating that they occur via AP1 antagonism within the VHT. Furthermore, the improved glucose tolerance and insulin sensitivity persisted in aged animals overexpressing ΔFosB in the VHT. These beneficial effects on glucose metabolism were abolished by peripheral sympathectomy and α-adrenergic, but not β-adrenergic, blockade. Taken together, our results show that antagonizing AP1 transcription activity in the VHT leads to a marked improvement in whole body glucose homeostasis via activation of the SNS, conferring protection against age-related impairment in glucose metabolism. These findings may open novel avenues for therapeutic intervention in diabetes and age-related glucose intolerance.
Published Version: doi:10.18632/aging.101157
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5361668/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:32071919
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)


Search DASH

Advanced Search