Modeling fat cell stresses: paving the way for improved management of obesity and diabetes

Abstract

now well recognized as interdependent diseases, are leading preventable causes of mortality and morbidity worldwide, with increasing prevalences in adults as well as in children [1]. National health authorities now view both obesity and diabetes as being two of the most serious public health problems of the 21st century, especially given the inter-relationships between these diseases and hypertension, atherosclerosis and dyslipidemia. Understanding the function of adipose tissue is key to successfully addressing these problems. Adipose tissue is a complex organ that, other than serving as a means for energy storage in the form of triglycerides, is able to secrete hormones and cytokines [2]. The increased mass of adipose tissue, which is characteristic of obesity, is due to hypertrophy of adipocytes and also an increase in the number of adipocytes, as is evident from tissue histology [3]. The number of adipocytes can increase through mitosis (mostly in adipocytes that have not yet started to produce lipids) or through differentiation from preadipocyte cells. Despite the fact that it is unknown which of these two mechanisms actually functions, or which is more dominant in humans in vivo, it is often hypothesized that maturation of preadipocytes into adipocytes is an important cause of obesity [4,5]. Adipogenesis is initiated and regulated through the activation of key transcription factors such as peroxisome proliferator-activated receptor (PPAR)-g 2 , which is an adipocyte-specific nuclear hormone receptor/adipogenic transcription factor, and through subsequent cascades of biochemical signaling involving members of the CCAAT/enhancer-binding protein family and the Kruppel-like factor family, as well as several extracellular-mediated signaling pathways [6]. Lipolysis, the breakdown of lipids stored in the adipocytes, occurs in response to signaling from other tissues that are energetically deprived, and involves hydrolization of triglycerides to glycerol and fatty acids (each triglyceride molecule breaks into one glycerol and three fatty acid molecules) [7]. Other than responding to stimuli caused by energy deprivation at other tissues in the body, adipocytes also go through a basal lipolytic activity, which is mediated primarily by expression of adipose triglyceride lipase [8].