Secretin-Activated Brown Fat Mediates Prandial Thermogenesis to Induce Satiation

被引：167

作者：

Li, Yongguo ^{[1
,2
]}

Schnabl, Katharina ^{[1
,2
,3
]}

Gabler, Sarah-Madeleine ^{[1
,2
,3
]}

Willershaeuser, Monja ^{[1
,2
]}

Reber, Josefine ^{[4
,5
]}

Karlas, Angelos ^{[4
,5
]}

Laurila, Sanna ^{[6
]}

Lahesmaa, Minna ^{[6
]}

Din, Mueez U. ^{[6
]}

Bast-Habersbrunner, Andrea ^{[1
,2
]}

Virtanen, Kirsi A. ^{[6
]}

Fromme, Tobias ^{[1
,2
,3
]}

Bolze, Florian ^{[1
,2
]}

O'Farrell, Libbey S. ^{[7
]}

Alsina-Fernandez, Jorge ^{[7
]}

Coskun, Tamer ^{[7
]}

Ntziachristos, Vasilis ^{[4
,5
]}

Nuutila, Pirjo ^{[6
,8
]}

Klingenspor, Martin ^{[1
,2
,3
]}

机构：

[1] Tech Univ Munich, TUM Sch Life Sci, Chair Mol Nutr Med, Freising Weihenstephan, Germany

[2] Tech Univ Munich, EKFZ Else Kroner Fresenius Ctr Nutr Med, Freising Weihenstephan, Germany

[3] Tech Univ Munich, ZIEL Inst Food & Hlth, Freising Weihenstephan, Germany

[4] Helmholtz Zentrum Munchen, IBMI, Neuherberg, Germany

[5] Tech Univ Munich, Chair Biol Imaging, Munich, Germany

[6] Univ Turku, Turku PET Ctr, Turku, Finland

[7] Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA

[8] Turku Univ Hosp, Dept Endocrinol, Turku, Finland

来源：

CELL | 2018年 / 175卷 / 06期

基金：

欧洲研究理事会; 芬兰科学院;

关键词：

ADIPOSE-TISSUE THERMOGENESIS; FOOD-INTAKE; COLD-ACCLIMATION; GASTROINTESTINAL HORMONES; INSULIN SENSITIVITY; ENERGY-EXPENDITURE; GLUCOSE; MEAL; ADIPOCYTES; HUMANS;

D O I：

10.1016/j.cell.2018.10.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The molecular mediator and functional significance of meal-assosiated brown fat (BAT) thermogenesis remains elusive. Here, we identified the gut hormone secretin as a non-synmpathetic BAT activator mediating prandial thermogenesis, which consequentially induces satiation, thereby establishing a gut-secretin-BAT-brain axis in mammals with a physiological role of prandial thermogenesis in the control of satiation. Mechanistically, meal-associated rise in circulating secretin activates BAT thermogenesis by stimulating lipolysis upon binding to secretin receptors in brown adipocytes, is sensed in the brain and promotes satiation. Chronic infusion of a modified human secretin transiently elevates energy expenditure in diet-induced obese mice. Clinical trials with human subjects showed that thermogenesis after a single-meal ingestion correlated with postprandial secretin levels and that secretin infusions increased glucose uptake in BAT. Collectively, our findings highlight the largely unappreciated function of BAT in the control of satiation and qualify BAT as an even more attractive target for treating obesity.

引用

页码：1561 / +

页数：26

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