A Role for Hypocretin/Orexin in Metabolic and Sleep Abnormalities in a Mouse Model of Non-metastatic Breast Cancer

被引：60

作者：

Borniger, Jeremy C. ^{[1
,2
,3
]}

Walker, William H., II ^{[1
,2
,3
]}

Surbhi ^{[1
,2
,3
]}

Emmer, Kathryn M. ^{[1
,2
,3
,6
]}

Zhang, Ning ^{[1
,2
,3
]}

Zalenski, Abigail A. ^{[1
,2
,3
]}

Muscarella, Stevie L. ^{[1
,2
,3
]}

Fitzgerald, Julie A. ^{[1
,2
,3
]}

Smith, Alexandra N. ^{[1
,2
,3
]}

Braam, Cornelius J. ^{[1
,2
,3
]}

TinKai, Tial ^{[1
,2
,3
]}

Magalang, Ulysses J. ^{[1
,2
,4
]}

Lustberg, Maryam B. ^{[5
]}

Nelson, Randy J. ^{[1
,2
,3
]}

DeVries, A. Courtney ^{[1
,2
,3
]}

机构：

[1] Ohio State Univ, Wexner Med Ctr, Dept Neurosci, Columbus, OH 43210 USA

[2] Ohio State Univ, Wexner Med Ctr, Neurosci Res Inst, Columbus, OH 43210 USA

[3] Ohio State Univ, Wexner Med Ctr, Behav Neuroendocrinol Grp, Columbus, OH 43210 USA

[4] Ohio State Univ, Dept Med, Wexner Med Ctr, Columbus, OH 43210 USA

[5] Ohio State Univ, Wexner Med Ctr, Div Med Oncol, Comprehens Canc Ctr, Columbus, OH 43210 USA

[6] Ohio State Univ, Wexner Med Ctr, Dept Vet Preventat Med, Columbus, OH 43210 USA

来源：

CELL METABOLISM | 2018年 / 28卷 / 01期

关键词：

OREXIN NEURONS; INFLAMMATION; SYSTEM; GHRELIN; COMMON;

D O I：

10.1016/j.cmet.2018.04.021

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We investigated relationships among immune, metabolic, and sleep abnormalities in mice with non-metastatic mammary cancer. Tumor-bearing mice displayed interleukin-6 (IL-6)-mediated peripheral inflammation, coincident with altered hepatic glucose processing and sleep. Tumor-bearing mice were hyperphagic, had reduced serum leptin concentrations, and enhanced sensitivity to exogenous ghrelin. We tested whether these phenotypes were driven by inflammation using neutralizing monoclonal antibodies against IL-6; despite the reduction in IL-6 signaling, metabolic and sleep abnormalities persisted. We next investigated neural populations coupling metabolism and sleep, and observed altered activity within lateral-hypothalamic hypocretin/orexin (HO) neurons. Weused a dual HO-receptor antagonist to test whether increased HO signaling was causing metabolic abnormalities. This approach rescued metabolic abnormalities and enhanced sleep quality in tumor-bearing mice. Peripheral sympathetic denervation prevented tumor-induced increases in serum glucose. Our results link metabolic and sleep abnormalities via the HO system, and provide evidence that central neuromodulators contribute to tumor-induced changes in metabolism.

引用

页码：118 / +

页数：17

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