Liza Makowski1, Gökhan S Hotamisligil. 1. Sarah W. Stedman Nutrition and Metabolism Center, Department of Medicine, Division of Endocrinology, Metabolism, and Nutrition, Duke University Medical Center, Durham, NC 27704, USA.
Abstract
PURPOSE OF REVIEW: The global prevalence of obesity is increasing epidemically. Obesity causes an array of health problems, reduces life expectancy, and costs over US dollar 100 billion annually. More than a quarter of the population suffers from an aggregation of co-morbidities, including obesity, atherosclerosis, insulin resistance, dyslipidemias, coagulopathies, hypertension, and a pro-inflammatory state known as the metabolic syndrome. Patients with metabolic syndrome have high risk of atherosclerosis as well as type 2 diabetes and other health problems. Like obesity, atherosclerosis has very limited therapeutic options. RECENT FINDINGS: Fatty acid binding proteins integrate metabolic and immune responses and link the inflammatory and lipid-mediated pathways that are critical in the metabolic syndrome. This review will highlight recent studies on fatty acid binding protein-deficient models and several fatty acid binding protein-mediated pathways specifically modified in macrophages, cells that are paramount to the initiation and persistence of cardiovascular lesions. SUMMARY: Adipocyte/macrophage fatty acid binding proteins, aP2 and mal1, act at the interface of metabolic and inflammatory pathways. These fatty acid binding proteins are involved in the formation of atherosclerosis predominantly through the direct modification of macrophage cholesterol trafficking and inflammatory responses. In addition to atherosclerosis, these fatty acid binding proteins also exert a dramatic impact on obesity, insulin resistance, type 2 diabetes and fatty liver disease. The creation of pharmacological agents to modify fatty acid binding protein function will provide tissue or cell-type-specific control of these lipid signaling pathways, inflammatory responses, atherosclerosis, and the other components of the metabolic syndrome, therefore offering a new class of multi-indication therapeutic agents.
PURPOSE OF REVIEW: The global prevalence of obesity is increasing epidemically. Obesity causes an array of health problems, reduces life expectancy, and costs over US dollar 100 billion annually. More than a quarter of the population suffers from an aggregation of co-morbidities, including obesity, atherosclerosis, insulin resistance, dyslipidemias, coagulopathies, hypertension, and a pro-inflammatory state known as the metabolic syndrome. Patients with metabolic syndrome have high risk of atherosclerosis as well as type 2 diabetes and other health problems. Like obesity, atherosclerosis has very limited therapeutic options. RECENT FINDINGS: Fatty acid binding proteins integrate metabolic and immune responses and link the inflammatory and lipid-mediated pathways that are critical in the metabolic syndrome. This review will highlight recent studies on fatty acid binding protein-deficient models and several fatty acid binding protein-mediated pathways specifically modified in macrophages, cells that are paramount to the initiation and persistence of cardiovascular lesions. SUMMARY: Adipocyte/macrophage fatty acid binding proteins, aP2 and mal1, act at the interface of metabolic and inflammatory pathways. These fatty acid binding proteins are involved in the formation of atherosclerosis predominantly through the direct modification of macrophage cholesterol trafficking and inflammatory responses. In addition to atherosclerosis, these fatty acid binding proteins also exert a dramatic impact on obesity, insulin resistance, type 2 diabetes and fatty liver disease. The creation of pharmacological agents to modify fatty acid binding protein function will provide tissue or cell-type-specific control of these lipid signaling pathways, inflammatory responses, atherosclerosis, and the other components of the metabolic syndrome, therefore offering a new class of multi-indication therapeutic agents.
Authors: Steven E Nissen; E Murat Tuzcu; Paul Schoenhagen; Tim Crowe; William J Sasiela; John Tsai; John Orazem; Raymond D Magorien; Charles O'Shaughnessy; Peter Ganz Journal: N Engl J Med Date: 2005-01-06 Impact factor: 91.245
Authors: Romeo Ricci; Grzegorz Sumara; Izabela Sumara; Izabela Rozenberg; Michael Kurrer; Alexander Akhmedov; Martin Hersberger; Urs Eriksson; Franz R Eberli; Burkhard Becher; Jan Borén; Mian Chen; Myron I Cybulsky; Kathryn J Moore; Mason W Freeman; Erwin F Wagner; Christian M Matter; Thomas F Lüscher Journal: Science Date: 2004-11-26 Impact factor: 47.728
Authors: L Scheja; L Makowski; K T Uysal; S M Wiesbrock; D R Shimshek; D S Meyers; M Morgan; R A Parker; G S Hotamisligil Journal: Diabetes Date: 1999-10 Impact factor: 9.461
Authors: Andrew C Li; Christoph J Binder; Alejandra Gutierrez; Kathleen K Brown; Christine R Plotkin; Jennifer W Pattison; Annabel F Valledor; Roger A Davis; Timothy M Willson; Joseph L Witztum; Wulf Palinski; Christopher K Glass Journal: J Clin Invest Date: 2004-12 Impact factor: 14.808
Authors: Nancy Levin; Eric D Bischoff; Chris L Daige; Diane Thomas; Calvin T Vu; Richard A Heyman; Rajendra K Tangirala; Ira G Schulman Journal: Arterioscler Thromb Vasc Biol Date: 2004-11-11 Impact factor: 8.311