Obesity is a multifactorial illness with severe associated metabolic comorbidities whose prevalence is increasing throughout the world at an alarming rate. Most of the pathophysiology of insulin resistance and, indeed, Type 2 diabetes begins with excess of energy intake and, in most cases, enlargement of adipocytes. Inflammatory changes occurring in expanding adipose tissue are associated with increased lipolysis and the secretion of peptide and other factors that can adversely affect metabolic processes in other key insulin-target tissues, especially the liver and skeletal muscle.
The main goal of my research is the study of the mechanisms underlying how RAGE regulates adiposity. We have recently shown that RAGE contributes to the development of adiposity and obesity, at least in part via reduction in metabolic rate and energy expenditure. An efficient mechanism to dissipate energy is through brown adipocytes, which are located at the brown adipose tissue and also interspersed within the white adipose tissue. Our data revealed fundamental metabolic sensing roles for RAGE in response to high fat diet feeding and suggest that blockade of RAGE may be a rational strategy for prevention of diet induced obesity and metabolic dysfunction.
1. Tinahones FJ, Coín-Aragüez L, Mayas MD, Garcia-Fuentes E, Hurtado-Del-Pozo C, Vendrell J, Cardona F, Calvo RM, Obregon MJ, El Bekay R. Obesity-associated insulin resistance is correlated to adipose tissue vascular endothelial growth factors and metalloproteinase levels. BMC Physiol. 2012 Apr 2. 12:4. doi: 10.1186/1472-6793-12-4.
2. Hurtado del Pozo C, Vesperinas-García G, Rubio MÁ, Corripio-Sánchez R, Torres-García AJ, Obregon MJ, Calvo RM. ChREBP expression in the liver, adipose tissue and differentiated preadipocytes in human obesity. Biochim Biophys Acta. 2011 Dec; 1811(12):1194-200. Epub 2011 Jul 30.
3. Hurtado del Pozo C, Calvo RM, Vesperinas G, Gómez Ambrosi J, Fruhbeck G, Rubio MA, Obregon MJ. Expression profile in omental and subcutaneous adipose tissue from lean and obese subjects. Repression of lipolytic and lipogenic genes. Obes Surg. 2011 May; 21(5):633-43.
4. Hurtado del Pozo C, Calvo RM, Vesperinas-García G, Gómez-Ambrosi J, Frühbeck G, Corripio-Sánchez R, Rubio MA, Obregon MJ. IPO8 and FBXL10: new reference genes for gene expression studies in human adipose tissue. Obesity (Silver Spring). 2010 May; 18(5):897-903. Epub 2009 Oct 29.
Dissipating energy stores by promoting thermogenic capacity in white adipose tissue has been proposed as an approach to treating obesity and its complications. My current research focuses on hypothesis that RAGE could regulate the conversion of white to brown adipocyte.