Differences in AMPK expression between subcutaneous and visceral adipose tissue in morbid obesity O. Martínez-Agustin a , J.J. Hernández-Morante b , E. Martínez-Plata a , F. Sánchez de Medina c , M. Garaulet b, ⁎ a Department of Biochemistry and Molecular Biology II, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBER-EHD), School of Pharmacy, University of Granada, Spain b Department of Physiology, University of Murcia, Murcia, Spain c Department of Pharmacology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBER-EHD), School of Pharmacy, University of Granada, Spain abstract article info Article history: Received 30 September 2009 Received in revised form 21 April 2010 Accepted 28 April 2010 Available online 10 May 2010 Keywords: Adenine monophosphate activated protein kinase Adiponectin Adipose tissue Morbid obesity Metabolic syndrome Adenine monophosphate (AMP) activated protein kinase (AMPK) is an important regulator of obesity. The objective of the present work was to study and compare AMPK protein expression in visceral vs. subcutaneous adipose tissue of morbid obese subjects and to correlate it with adipose tissue characteristics. We selected a total population of 17 extreme obese (BMI ≥ 40 kg/m 2 ) aged 42.8 ± 10.2 years were included in this study. We measured anthropometric and body composition parameters. Adiponectin expression by qRT-PCR, isoproterenol-stimulated lipolytic rates, and AMPK alpha subunits expression by Western blot in adipose tissue explants were determined. Finally plasma concentrations of glucose, triacylglycerols, total cholesterol, HDL-c, LDL-c and insulin were also measured. Our results showed that AMPK alpha expression was higher in subcutaneous than in visceral tissue. A positive correlation between AMPK expression and adiponectin expression in human subcutaneous adipose tissue was observed. Furthermore, a positive correlation between AMPK expression and isoproterenol evoked upregulation of lipolysis rate was also observed. In conclusion, AMPK alpha expression differed according to adipose tissue location. The positive correlation between subcutaneous adipose tissue AMPK and adiponectin or the evoked lipolysis rate could indicate a protective role of AMPK in this tissue, counteracting insulin resistance in morbid obese patients. © 2010 Elsevier B.V. All rights reserved. 1. Introduction The adenine monophosphate (AMP) activated protein kinase (AMPK) is a heterotrimeric complex that is activated by an increase in the AMP/ATP ratio, and it constitutes a major regulator of energy metabolism at both the cell and the whole body level [1]. AMPK also participates in glycolysis regulation, glucose uptake, lipid oxidation, fatty acid synthesis, cholesterol synthesis and gluconeogenesis, and it has been considered as a possible target enzyme in the treatment of some diseases, such as type 2 diabetes and cardiovascular diseases [1–4]. Moreover, changes in AMPK activity have been reported in obesity and the metabolic syndrome (MetS) [5]. MetS is a cluster of clinical and biochemical abnormalities characterized by central obesity, dyslipidaemia (hypertriglyceridaemia and decreased HDL-C (high-density lipoprotein cholesterol)), glucose intolerance, insulin resistance and hypertension [6]. Adiponectin has been described as a “guardian angel” against MetS features [7]. Activation of the AMPK pathway, together with a subsequent increase in fatty acid oxidation, appears to constitute the main mechanism of action of adiponectin in the regulation of lipid metabolism [2]. In fact, decreased activation of AMPK seems to have a role in the appearance of the MetS [8]. In addition, alteration of AMPK signalling in the hypothalamus, which may function as a sensor of nutrient availability, integrating multiple nutritional and hormonal signals, may have a key role in total energy intake [8]. The distribution of body fat has a singular impact on the development of obesity-related alterations, mainly MetS and type 2 diabetes. In fact, abdominal adipose accumulation represents per se a risk factor [9]. Thus, both the localization and type of adipose tissue are crucial features. Indeed, visceral and subcutaneous depots differ considerably from the histological, physiological and metabolic point of view [10]. Many studies have focused on the metabolism of AMPK in muscle [11] and even in hypothalamus [12]. However, the particular mechanism whereby AMPK seems to exert its protective role against obesity-related alterations in human adipose tissue remains to be determined, even though this is the most abundant tissue in morbid obese patients. The aim of the present study was to analyze the differential protein levels of AMPK between subcutaneous and visceral adipose tissue from morbid obese individuals and to correlate it with adipose tissue characteristics such as adiponectin expression and lipolysis degree. Regulatory Peptides 163 (2010) 31–36 ⁎ Corresponding author. Department of Physiology, University of Murcia, Campus de Espinardo, 30100 Murcia, Spain. Tel.: +34 968 363930; fax: +34 968 363963. E-mail address: garaulet@um.es (M. Garaulet). 0167-0115/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.regpep.2010.04.008 Contents lists available at ScienceDirect Regulatory Peptides journal homepage: www.elsevier.com/locate/regpep