Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance

被引：551

作者：

Lopez, Miguel ^{[1
,2
,3
]}

Varela, Luis ^{[1
,2
]}

Vazquez, Maria J. ^{[1
,2
]}

Rodriguez-Cuenca, Sergio ^{[3
]}

Gonzalez, Carmen R. ^{[1
,2
]}

Velagapudi, Vidya R. ^{[4
]}

Morgan, Donald A. ^{[5
]}

Schoenmakers, Erik ^{[3
]}

Agassandian, Khristofor ^{[6
]}

Lage, Ricardo ^{[1
,2
]}

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

Tovar, Sulay ^{[1
,2
]}

Nogueiras, Ruben ^{[1
,2
]}

Carling, David ^{[7
]}

Lelliott, Christopher ^{[8
]}

Gallego, Rosalia ^{[9
]}

Oresic, Matej ^{[4
]}

Chatterjee, Krishna

Saha, Asish K. ^{[10
]}

Rahmouni, Kamal ^{[5
]}

Dieguez, Carlos ^{[1
,2
]}

Vidal-Puig, Antonio ^{[3
]}

机构：

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

[2] Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, La Coruna, Spain

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

[4] Tech Res Ctr Finland VTT, Espoo, Finland

[5] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA

[6] Univ Iowa, Dept Anat & Cell Biol, Carver Coll Med, Iowa City, IA 52242 USA

[7] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Ctr Clin Sci, MRC,Cellular Stress Grp, London, England

[8] AstraZeneca, Res & Dev, Dept Biosci, Molndal, Sweden

[9] Univ Santiago de Compostela, Sch Med, Dept Morphol Sci, Santiago De Compostela, A Coruna, Spain

[10] Boston Med Ctr, Diabet Res Unit, Boston, MA USA

来源：

NATURE MEDICINE | 2010年 / 16卷 / 09期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

BROWN ADIPOSE-TISSUE; ACTIVATED PROTEIN-KINASE; ACETYL-COA CARBOXYLASE; FOOD-INTAKE; VENTROMEDIAL HYPOTHALAMUS; INSULIN SENSITIVITY; SKELETAL-MUSCLE; NERVOUS-SYSTEM; ADULT HUMANS; MALONYL-COA;

D O I：

10.1038/nm.2207

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：

Thyroid hormones have widespread cellular effects; however it is unclear whether their effects on the central nervous system (CNS) contribute to global energy balance. Here we demonstrate that either whole-body hyperthyroidism or central administration of triiodothyronine (T3) decreases the activity of hypothalamic AMP-activated protein kinase (AMPK), increases sympathetic nervous system (SNS) activity and upregulates thermogenic markers in brown adipose tissue (BAT). Inhibition of the lipogenic pathway in the ventromedial nucleus of the hypothalamus (VMH) prevents CNS-mediated activation of BAT by thyroid hormone and reverses the weight loss associated with hyperthyroidism. Similarly, inhibition of thyroid hormone receptors in the VMH reverses the weight loss associated with hyperthyroidism. This regulatory mechanism depends on AMPK inactivation, as genetic inhibition of this enzyme in the VMH of euthyroid rats induces feeding-independent weight loss and increases expression of thermogenic markers in BAT. These effects are reversed by pharmacological blockade of the SNS. Thus, thyroid hormone-induced modulation of AMPK activity and lipid metabolism in the hypothalamus is a major regulator of whole-body energy homeostasis.

引用

页码：1001 / U97

页数：9

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