Nicotine induces negative energy balance through hypothalamic AMP-activated protein kinase

Pablo Blanco Martinez De Morentin, Andrew J Whittle, Johan Fernø, Rubén Nogueiras, Carlos Diéguez, Antonio Vidal-Puig, Miguel López

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)807-817
Number of pages11
JournalDiabetes
Volume61
Issue number4
Early online date7 Feb 2012
DOIs
Publication statusPublished - Apr 2012

Fingerprint

AMP-Activated Protein Kinases
Nicotine
Brown Adipose Tissue
Hypothalamus
Appetite Depressants
Thermogenesis
Smoking Cessation
Locomotion
Energy Metabolism
Weight Loss
Rodentia
Homeostasis
Central Nervous System
Obesity
Body Weight

Keywords

  • AMP-Activated Protein Kinases
  • Adipose Tissue, Brown
  • Animals
  • Appetite
  • Eating
  • Energy Metabolism
  • Gene Expression Regulation
  • Hypothalamus
  • Male
  • Motor Activity
  • Neuropeptide Y
  • Nicotine
  • Pro-Opiomelanocortin
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Nicotinic
  • Temazepam
  • Thermogenesis

Cite this

Martinez De Morentin, P. B., Whittle, A. J., Fernø, J., Nogueiras, R., Diéguez, C., Vidal-Puig, A., & López, M. (2012). Nicotine induces negative energy balance through hypothalamic AMP-activated protein kinase. Diabetes, 61(4), 807-817. https://doi.org/10.2337/db11-1079

Nicotine induces negative energy balance through hypothalamic AMP-activated protein kinase. / Martinez De Morentin, Pablo Blanco; Whittle, Andrew J; Fernø, Johan; Nogueiras, Rubén; Diéguez, Carlos; Vidal-Puig, Antonio; López, Miguel.

In: Diabetes, Vol. 61, No. 4, 04.2012, p. 807-817.

Research output: Contribution to journalArticle

Martinez De Morentin, PB, Whittle, AJ, Fernø, J, Nogueiras, R, Diéguez, C, Vidal-Puig, A & López, M 2012, 'Nicotine induces negative energy balance through hypothalamic AMP-activated protein kinase', Diabetes, vol. 61, no. 4, pp. 807-817. https://doi.org/10.2337/db11-1079
Martinez De Morentin, Pablo Blanco ; Whittle, Andrew J ; Fernø, Johan ; Nogueiras, Rubén ; Diéguez, Carlos ; Vidal-Puig, Antonio ; López, Miguel. / Nicotine induces negative energy balance through hypothalamic AMP-activated protein kinase. In: Diabetes. 2012 ; Vol. 61, No. 4. pp. 807-817.
@article{ffc10931adbf42238cf7eb104d0ad468,
title = "Nicotine induces negative energy balance through hypothalamic AMP-activated protein kinase",
abstract = "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.",
keywords = "AMP-Activated Protein Kinases, Adipose Tissue, Brown, Animals, Appetite, Eating, Energy Metabolism, Gene Expression Regulation, Hypothalamus, Male, Motor Activity, Neuropeptide Y, Nicotine, Pro-Opiomelanocortin, Rats, Rats, Sprague-Dawley, Receptors, Nicotinic, Temazepam, Thermogenesis",
author = "{Martinez De Morentin}, {Pablo Blanco} and Whittle, {Andrew J} and Johan Fern{\o} and Rub{\'e}n Nogueiras and Carlos Di{\'e}guez and Antonio Vidal-Puig and Miguel L{\'o}pez",
year = "2012",
month = "4",
doi = "10.2337/db11-1079",
language = "English",
volume = "61",
pages = "807--817",
journal = "Diabetes",
issn = "0012-1797",
publisher = "AMER DIABETES ASSOC",
number = "4",

}

TY - JOUR

T1 - Nicotine induces negative energy balance through hypothalamic AMP-activated protein kinase

AU - Martinez De Morentin, Pablo Blanco

AU - Whittle, Andrew J

AU - Fernø, Johan

AU - Nogueiras, Rubén

AU - Diéguez, Carlos

AU - Vidal-Puig, Antonio

AU - López, Miguel

PY - 2012/4

Y1 - 2012/4

N2 - 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.

AB - 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.

KW - AMP-Activated Protein Kinases

KW - Adipose Tissue, Brown

KW - Animals

KW - Appetite

KW - Eating

KW - Energy Metabolism

KW - Gene Expression Regulation

KW - Hypothalamus

KW - Male

KW - Motor Activity

KW - Neuropeptide Y

KW - Nicotine

KW - Pro-Opiomelanocortin

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptors, Nicotinic

KW - Temazepam

KW - Thermogenesis

U2 - 10.2337/db11-1079

DO - 10.2337/db11-1079

M3 - Article

VL - 61

SP - 807

EP - 817

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 4

ER -