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

• Published in: Endocrinology (Philadelphia) 2014-05, Vol.155 (5), p.1679-1689
• Main Authors: Seoane-Collazo, Patricia, de Morentin, Pablo B. Martínez, Fernø, Johan, Diéguez, Carlos, Nogueiras, Rubén, López, Miguel
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose tissue (brown); Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - metabolism; AMP-activated protein kinase; AMP-Activated Protein Kinases - antagonists & inhibitors; AMP-Activated Protein Kinases - metabolism; Animal models; Animals; Appetite Depressants - administration & dosage; Appetite Depressants - adverse effects; Appetite Depressants - therapeutic use; Appetite Regulation - drug effects; Body fat; Body weight; Body weight loss; Central nervous system; Diet; Diet, Fat-Restricted; Diet, High-Fat - adverse effects; Dyslipidemias - etiology; Dyslipidemias - prevention & control; Endoplasmic reticulum; Endoplasmic Reticulum Stress - drug effects; Energy balance; Fatty liver; Fatty Liver - etiology; Fatty Liver - prevention & control; Food intake; High fat diet; Homeostasis; Hyperinsulinism - etiology; Hyperinsulinism - prevention & control; Hypothalamus; Hypothalamus - drug effects; Hypothalamus - enzymology; Hypothalamus - metabolism; Injections, Subcutaneous; Kinases; Lipids; Liver - drug effects; Liver - enzymology; Liver - metabolism; Liver - pathology; Liver diseases; Low fat diet; Low protein diet; Male; Metabolic disorders; Metabolism; Nervous system; Nicotine; 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; Nutrient deficiency; Obesity; Obesity - diet therapy; Obesity - drug therapy; Obesity - etiology; Obesity - metabolism; Proteins; Rats; Rats, Sprague-Dawley; Resistance factors; Serum levels; Steatosis; Sympathetic nervous system; Thermogenesis; Thermogenesis - drug effects; Tobacco; Weight control; Weight loss; Weight Loss - drug effects; Weight reduction
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2013-1839

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.