Nicotine Induces Negative Energy Balance Through Hypothalamic AMP-Activated Protein Kinase

被引：143

作者：

Martinez de Morentin, Pablo B. ^{[1
,2
]}

Whittle, Andrew J. ^{[3
]}

Ferno, Johan ^{[4
,5
]}

Nogueiras, Ruben ^{[1
,2
]}

Dieguez, Carlos ^{[1
,2
]}

Vidal-Puig, Antonio ^{[3
]}

Lopez, Miguel ^{[1
,2
]}

机构：

[1] Univ Santiago de Compostela, Inst Invest Sanitaria, Sch Med, Dept Physiol,CIMUS, Santiago De Compostela, A Coruna, Spain

[2] CIBER Fisiopatol Obesidad & Nutr CIBERobn, Santiago De Compostela, Spain

[3] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs,NIHR Cambridge Biomed Res Ctr, Cambridge CB2 2QQ, England

[4] Univ Bergen, Dept Clin Med, Dr Einar Martens Res Grp Biol Psychiat, Bergen, Norway

[5] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway

来源：

DIABETES | 2012年 / 61卷 / 04期

基金：

英国生物技术与生命科学研究理事会;

关键词：

BROWN ADIPOSE-TISSUE; NEUROPEPTIDE-Y; FOOD-INTAKE; UNCOUPLING PROTEIN-1; BODY-WEIGHT; EXPRESSION; LEPTIN; NPY; INHIBITION; PATHWAYS;

D O I：

10.2337/db11-1079

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Smokers around the world commonly report increased body weight after smoking cessation as a major factor that interferes with their attempts to quit. Numerous controlled studies in both humans and rodents have reported that nicotine exerts a marked anorectic action. The effects of nicotine on energy homeostasis have been mostly pinpointed in the central nervous system, but the molecular mechanisms controlling its action are still not fully understood. The aim of this study was to investigate the effect of nicotine on hypothalamic AMP-activated protein kinase (AMPK) and its effect on energy balance. Here we demonstrate that nicotine-induced weight loss is associated with inactivation of hypothalamic AMPK, decreased orexigenic signaling in the hypothalamus, increased energy expenditure as a result of increased locomotor activity, increased thermogenesis in brown adipose tissue (BAT), and alterations in fuel substrate utilization. Conversely, nicotine withdrawal or genetic activation of hypothalamic AMPK in the ventromedial nucleus of the hypothalamus reversed nicotine-induced negative energy balance. Overall these data demonstrate that the effects of nicotine on energy balance involve specific modulation of the hypothalamic AMPK-BAT axis. These targets may be relevant for the development of new therapies for human obesity. Diabetes 61:807-817, 2012

引用

页码：807 / 817

页数：11