Nicotine Improves Obesity and Hepatic Steatosis and ER Stress in Diet-Induced Obese Male Rats

Endocrinology. 2014 May;155(5):1679-89. doi: 10.1210/en.2013-1839. Epub 2014 Feb 11.

Abstract

Nicotine, the main addictive component of tobacco, promotes body weight reduction in humans and rodents. Recent evidence has suggested that nicotine acts in the central nervous system to modulate energy balance. Specifically, nicotine modulates hypothalamic AMP-activated protein kinase to decrease feeding and to increase brown adipose tissue thermogenesis through the sympathetic nervous system, leading to weight loss. Of note, most of this evidence has been obtained in animal models fed with normal diet or low-fat diet (LFD). However, its effectiveness in obese models remains elusive. Because obesity causes resistance towards many factors involved in energy homeostasis, the aim of this study has been to compare the effect of nicotine in a diet-induced obese (DIO) model, namely rats fed a high-fat diet, with rats fed a LFD. Our data show that chronic peripheral nicotine treatment reduced body weight by decreasing food intake and increasing brown adipose tissue thermogenesis in both LFD and DIO rats. This overall negative energy balance was associated to decreased activation of hypothalamic AMP-activated protein kinase in both models. Furthermore, nicotine improved serum lipid profile, decreased insulin serum levels, as well as reduced steatosis, inflammation, and endoplasmic reticulum stress in the liver of DIO rats but not in LFD rats. Overall, this evidence suggests that nicotine diminishes body weight and improves metabolic disorders linked to DIO and might offer a clear-cut strategy to develop new therapeutic approaches against obesity and its metabolic complications.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / antagonists & inhibitors
  • AMP-Activated Protein Kinases / metabolism
  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Animals
  • Appetite Depressants / administration & dosage
  • Appetite Depressants / adverse effects
  • Appetite Depressants / therapeutic use*
  • Appetite Regulation / drug effects*
  • Diet, Fat-Restricted
  • Diet, High-Fat / adverse effects
  • Dyslipidemias / etiology
  • Dyslipidemias / prevention & control
  • Endoplasmic Reticulum Stress / drug effects*
  • Fatty Liver / etiology
  • Fatty Liver / prevention & control*
  • Hyperinsulinism / etiology
  • Hyperinsulinism / prevention & control
  • Hypothalamus / drug effects
  • Hypothalamus / enzymology
  • Hypothalamus / metabolism
  • Injections, Subcutaneous
  • Liver / drug effects
  • Liver / enzymology
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Nicotine / administration & dosage
  • Nicotine / adverse effects
  • Nicotine / therapeutic use*
  • Nicotinic Agonists / administration & dosage
  • Nicotinic Agonists / adverse effects
  • Nicotinic Agonists / therapeutic use*
  • Non-alcoholic Fatty Liver Disease
  • Obesity / diet therapy
  • Obesity / drug therapy*
  • Obesity / etiology
  • Obesity / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Thermogenesis / drug effects
  • Weight Loss / drug effects

Substances

  • Appetite Depressants
  • Nicotinic Agonists
  • Nicotine
  • AMP-Activated Protein Kinases