Abstract
Obesity and the associated comorbidities are a growing health threat worldwide. Adipose tissue dysfunction, impaired adipokine activity, and inflammation are central to metabolic diseases related to obesity. In particular, the excess storage of lipids in adipose tissues disturbs cellular homeostasis. Amongst others, organelle function and cell signaling, often related to the altered composition of specialized membrane microdomains (lipid rafts), are affected. Within this context, the conserved family of annexins are well known to associate with membranes in a calcium (Ca2+)- and phospholipid-dependent manner in order to regulate membrane-related events, such as trafficking in endo- and exocytosis and membrane microdomain organization. These multiple activities of annexins are facilitated through their diverse interactions with a plethora of lipids and proteins, often in different cellular locations and with consequences for the activity of receptors, transporters, metabolic enzymes, and signaling complexes. While increasing evidence points at the function of annexins in lipid homeostasis and cell metabolism in various cells and organs, their role in adipose tissue, obesity and related metabolic diseases is still not well understood. Annexin A1 (AnxA1) is a potent pro-resolving mediator affecting the regulation of body weight and metabolic health. Relevant for glucose metabolism and fatty acid uptake in adipose tissue, several studies suggest AnxA2 to contribute to coordinate glucose transporter type 4 (GLUT4) translocation and to associate with the fatty acid transporter CD36. On the other hand, AnxA6 has been linked to the control of adipocyte lipolysis and adiponectin release. In addition, several other annexins are expressed in fat tissues, yet their roles in adipocytes are less well examined. The current review article summarizes studies on the expression of annexins in adipocytes and in obesity. Research efforts investigating the potential role of annexins in fat tissue relevant to health and metabolic disease are discussed.
Highlights
In most countries, the increasing prevalence of obesity represents a rapidly growing risk factor for chronic liver diseases, type 2 diabetes (T2D), cardiovascular diseases and most types of cancer
In follow-up studies, we identified Annexin A6 (AnxA6)-induced cholesterol imbalance to cause mislocalization and dysfunction of several cholesterol-sensitive SNARE proteins in the secretory pathway [72,73], all of which are fundamental for the metabolic response that facilitates glucose transporter type 4 (GLUT4) translocation in adipocytes [124]
AnxA2 has been linked to the insulin-dependent translocation of GLUT4 as well as CD36-mediated fatty acid uptake [51,57,59], the latter providing a protective function in the postprandial state
Summary
The increasing prevalence of obesity represents a rapidly growing risk factor for chronic liver diseases, type 2 diabetes (T2D), cardiovascular diseases and most types of cancer. Adipose tissue is central to the development of obesity and is composed of different cell populations including fibroblasts, preadipocytes, mature adipocytes, macrophages, mesenchymal stem cells, endothelial cells, and vascular smooth muscle cells, with cellular function as well as their quantity being affected by obesity [1]. All these different cell types, through various mechanisms, contribute to obesity and associated comorbidities, which has been reviewed in detail elsewhere [1,2,3].
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