Anti-Obesity Drug Discovery and Development

Anti-Obesity Drug Discovery and Development

Volume: 2

Indexed in: EBSCO, Ulrich's Periodicals Directory

Obesity is a complex health problem, caused by a number of factors such as excessive food intake, lack of physical activity, genetic predisposition, endocrine disorders, medications and psychiatric ...
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An Approach to Obesity as a Cardiometabolic Disease: Potential Implications for Clinical Practice

Pp. 3-85 (83)

José Sabán-Ruíz, Martin Fabregate-Fuente, Rosa Fabregate-Fuente, Ana Alonso-Pacho, Cristina de la Puerta González-Quevedo, Susana Tello Blasco, Asunción Guerri and Alcira Andrés and Delia Barrio

Abstract

Obesity is a multifactorial disease that is currently developing a threatening tendency towards becoming the main cause of chronic disease in the world. Obesity can induce type 2 diabetes mellitus, dyslipidemia, cardiovascular disease and other chronic disorders with high social and health costs. Obesity was firstly described in 2000 as a cardiometabolic disease, even before Metabolic Syndrome, type 2 diabetes mellitus and coronary disease were considered as such. In this chapter we recover this approach to obesity, which has remained almost forgotten for the last decade. In obese subjects, adipokines and miokines interact to promote reticulum stress, insulin resistance, metabolic inflexibility and endothelial dysfunction. These pathological processes are amplified when hyperglycemia is present, leading to an increased risk for atherosclerosis. A number of potential implications for clinical practice are derived from the cardiometabolic state underlying obesity and its comorbidities. The first step in the therapeutic strategy against obesity should be the correct diagnosis of its causes and the promotion of lifestyle changes including physical exercise and a healthy diet. In the usual case of failing to achieve results, we can still resort to the pharmacological therapy. While awaiting the release of new drugs, topiramate, alone or combined with phentermine, has been proposed as a novel anti-obesity drug, showing relevant effects not only on weight loss but also on cardiometabolic alterations and biomarkers, even though new studies should clarify the mechanisms of these findings. Finally, our own experience with topiramate is described, focusing on its effects upon weight loss and inflammatory markers.

Keywords:

Adipokine, adiposity, adiposopathy endoplasmic reticulum stress, anti-obesity drugs, atherosclerosis, cardiometabolic disease, coronary heart disease, diet, endothelial dysfunction, inflammation, insulin resistance, lifestyle changes, metabolic inflexibility, miokine, obesity, physical activity, topiramate, weight loss.

Affiliation:

Endothelium and Cardiometabolic Medicine Unit, Internal Medicine Service, Ramón y Cajal Hospital, Madrid, Spain.