Suppression of food intake by Glp1r/Lepr-coexpressing neurons prevents obesity in mouse models

被引：12

作者：

Rupp, Alan C. ^{[1
]}

Tomlinson, Abigail J. ^{[1
]}

Affinati, Alison H. ^{[1
]}

Yacawych, Warren T. ^{[1
,2
]}

Duensing, Allison M. ^{[1
,2
]}

True, Cadence ^{[3
]}

Lindsley, Sarah R. ^{[3
]}

Kirigiti, Melissa A. ^{[3
]}

MacKenzie, Alexander ^{[1
]}

Polex-Wolf, Joseph ^{[4
]}

Li, Chien ^{[4
]}

Knudsen, Lotte Bjerre ^{[4
]}

Seeley, Randy J. ^{[5
]}

Olson, David P. ^{[6
]}

Kievit, Paul ^{[3
]}

Myers Jr, Martin G. ^{[1
,2
,7
]}

机构：

[1] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI USA

[3] Oregon Natl Primate Res Ctr, Beaverton, OR USA

[4] Novo Nordisk, Copenhagen, Denmark

[5] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA

[6] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA

[7] Univ Michigan, Sch Med, Dept Internal Med, Div Metab Endocrinol & Diabet, 2800 Plymouth Rd,Bldg 20,Room 2822, Ann Arbor, MI 48109 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2023年 / 133卷 / 19期

关键词：

LEPTIN ACTION; GLUCOSE-HOMEOSTASIS; BODY-WEIGHT; ENERGY-EXPENDITURE; HYPOTHALAMUS; NUCLEUS; INSULIN; SYSTEM; MICE;

D O I：

10.1172/JCI157515

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The adipose-derived hormone leptin acts via its receptor (LepRb) in the brain to control energy balance. A potentially unidentified population of GABAergic hypothalamic LepRb neurons plays key roles in the restraint of food intake and body weight by leptin. To identify markers for candidate populations of LepRb neurons in an unbiased manner, we performed single-nucleus RNA-Seq of enriched mouse hypothalamic LepRb cells, identifying several previously unrecognized populations of hypothalamic LepRb neurons. Many of these populations displayed strong conservation across species, Similarly, improvements in energy balance caused by Lepr reactivation in GABA neurons of otherwise Lepr-null mice required otherwise Glp1r-null mice enabled food intake suppression by the GLP1R agonist, liraglutide. Thus, the conserved GABAergic LepRbGlp1r neuron population plays crucial roles in the suppression of food intake by leptin and GLP1R agonists.

引用

页数：12

共 1 条

[1] Obesity medication lorcaserin activates brainstem GLP-1 neurons to reduce food intake and augments GLP-1 receptor agonist induced appetite suppression
Wagner, Stefan
Brierley, Daniel I.
Leeson-Payne, Alasdair
Jiang, Wanqing
Chianese, Raffaella
Lam, Brian Y. H.
Dowsett, Georgina K. C.
Cristiano, Claudia
Lyons, David
Reimann, Frank
Gribble, Fiona M.
de Morentin, Pablo B. Martinez
Yeo, Giles S. H.
Trapp, Stefan
Heisler, Lora K.
MOLECULAR METABOLISM, 2023, 68

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