Drp1 is required for AgRP neuronal activity and feeding

被引：18

作者：

Jin, Sungho ^{[1
]}

Yoon, Nal Ae ^{[1
]}

Liu, Zhong-Wu ^{[2
,3
]}

Song, Jae Eun ^{[2
,3
]}

Horvath, Tamas L. ^{[2
,3
]}

Kim, Jung Dae ^{[1
]}

Diano, Sabrina ^{[1
,4
,5
]}

机构：

[1] Columbia Univ, Inst Human Nutr, Irving Med Ctr, New York, NY 10032 USA

[2] Yale Univ, Sch Med, Dept Comparat Med, New Haven, CT USA

[3] Yale Univ, Program Integrat Cell Signaling & Neurobiol Metab, Sch Med, New Haven, CT USA

[4] Columbia Univ, Dept Mol Pharmacol & Therapeut, Irving Med Ctr, New York, NY 10027 USA

[5] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA

来源：

ELIFE | 2021年 / 10卷

关键词：

MITOCHONDRIAL DYNAMICS; ENERGY; FISSION; DISEASE; FUSION; LEPTIN;

D O I：

10.7554/eLife.64351

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The hypothalamic orexigenic Agouti-related peptide (AgRP)-expressing neurons are crucial for the regulation of whole-body energy homeostasis. Here, we show that fasting-induced AgRP neuronal activation is associated with dynamin-related peptide 1 (DRP1)-mediated mitochondrial fission and mitochondrial fatty acid utilization in AgRP neurons. In line with this, mice lacking Dnm1l in adult AgRP neurons (Drp1 cKO) show decreased fasting-or ghrelin-induced AgRP neuronal activity and feeding and exhibited a significant decrease in body weight, fat mass, and feeding accompanied by a significant increase in energy expenditure. In support of the role for mitochondrial fission and fatty acids oxidation, Drp1 cKO mice showed attenuated palmitic acid-induced mitochondrial respiration. Altogether, our data revealed that mitochondrial dynamics and fatty acids oxidation in hypothalamic AgRP neurons is a critical mechanism for AgRP neuronal function and body-weight regulation.

引用

页数：24

共 50 条

[41] Restraining the Divider: A Drp1-Phospholipid Interaction Inhibits Drp1 Activity and Shifts the Balance from Mitochondrial Fission to Fusion
Kashatus, David F.
MOLECULAR CELL, 2016, 63 (06) : 913 - 915
[42] Sustained inhibition of NPY/AgRP neuronal activity by FGF1
Hwang, Eunsang
Scarlett, Jarrad M.
Baquero, Arian F.
Bennett, Camdin M.
Dong, Yanbin
Chau, Dominic
Brown, Jenny M.
Mercer, Aaron J.
Meek, Thomas H.
Grove, Kevin L.
Phan, Bao Anh N.
Morton, Gregory J.
Williams, Kevin W.
Schwartz, Michael W.
JCI INSIGHT, 2022, 7 (17)
[43] RhoA Regulation of Drp1 and Cardiac Mitochondrial Fission
Brand, Cameron S.
Tan-Sah, Valerie P.
Brown, Joan Heller
Miyamoto, Shigeki
FASEB JOURNAL, 2016, 30
[44] Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria
Cereghetti, G. M.
Stangherlin, A.
de Brito, O. Martins
Chang, C. R.
Blackstone, C.
Bernardi, P.
Scorrano, L.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (41) : 15803 - 15808
[45] Inhibition of Drp1 provides neuroprotection in vitro and in vivo
J Grohm
S-W Kim
U Mamrak
S Tobaben
A Cassidy-Stone
J Nunnari
N Plesnila
C Culmsee
Cell Death & Differentiation, 2012, 19 : 1446 - 1458
[46] Inhibition of Drp1 provides neuroprotection in vitro and in vivo
Grohm, J.
Kim, S-W
Mamrak, U.
Tobaben, S.
Cassidy-Stone, A.
Nunnari, J.
Plesnila, N.
Culmsee, C.
CELL DEATH AND DIFFERENTIATION, 2012, 19 (09): : 1446 - 1458
[47] The role of Drp1 in adult skeletal muscle physiology
Dablainville, Valentin
Sanchez, Anthony M. J.
JOURNAL OF PHYSIOLOGY-LONDON, 2020, 598 (21): : 4761 - 4763
[48] Role of disordered regions on Drp1 structure and function
Hutson, Anelise
Mears, Jason A.
BIOPHYSICAL JOURNAL, 2024, 123 (03) : 67A - 67A
[49] Drp1—a regulator of mitochondrial dynamics in cardiorenal syndrome
Nature Reviews Nephrology, 2015, 11 (4) : 196 - 196
[50] Fis1 and Drp1 cooperate in mitochondrial homeostasis
Hill, Blake
Manlandro, Cara Marie
Cleland, Megan
Kennedy, Nolan
Bakkum, Amber
FASEB JOURNAL, 2014, 28 (01):

← 1 2 3 4 5 →