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World J Gastroenterol. Oct 14, 2010; 16(38): 4762-4772
Published online Oct 14, 2010. doi: 10.3748/wjg.v16.i38.4762
Fat: A matter of disturbance for the immune system
Alessandro Federico, Elena D’Aiuto, Francesco Borriello, Giusi Barra, Antonietta Gerarda Gravina, Marco Romano, Raffaele De Palma
Alessandro Federico, Antonietta Gerarda Gravina, Marco Romano, Section of Gastroenterology, Department of Clinical and Experimental Medicine, Second University of Naples, 80131 Napoli, Italy
Elena D’Aiuto, Francesco Borriello, Giusi Barra, Raffaele De Palma, Section of Clinical Immunology, Department of Clinical and Experimental Medicine, Second University of Naples, 80131 Napoli, Italy
Author contributions: Federico A, Romano M and De Palma R contributed equally to this work; Federico A, Gravina AG, Romano M, D’Aiuto E, Borriello F, Barra G and De Palma R revised the literature data; Federico A, Romano M and De Palma R wrote the manuscript.
Correspondence to: Raffaele De Palma, MD, PhD, Professor, Section of Clinical Immunology, Department of Clinical and Experimental Medicine, Second University of Naples, c/o II Policlinico (ed.3) via S. Pansini, 5, 80131 Napoli, Italy. raffaele.depalma@unina2.it
Telephone: +39-81-5666717 Fax: +39-81-5666732
Received: May 8, 2010
Revised: June 23, 2010
Accepted: June 30, 2010
Published online: October 14, 2010
Abstract

Obesity is increasingly being recognized as a risk factor for a number of benign and malignant gastrointestinal conditions. However, literature on the underlying pathophysiological mechanisms is sparse and ambiguous. There is compelling evidence that both overnutrition and undernutrition negatively interfere with the immune system. Overnutrition has been found to increase susceptibility to the development of inflammatory diseases, autoimmune diseases and cancer. In the regulation of immune and inflammatory processes, white adipose tissue plays a critical role, not only as an energy store but also as an important endocrine organ. The obese state is characterised by a low-grade systemic inflammation, mainly as a result of increased adipocytes as well as fat resident- and recruited-macrophage activity. In the past few years, various products of adipose tissue including adipokines and cytokines have been characterised and a number of pathways linking adipose tissue metabolism with the immune system have been identified. Activation of the innate immune system plays a major role in hepatic steatosis. Non-alcoholic fatty liver disease includes a wide spectrum of diseases, from pure steatosis to non-alcoholic steatohepatitis in the absence of significant alcohol consumption. Although steatosis is considered a non-progressive disease, non-alcoholic steatohepatitis may deteriorate in advanced chronic liver diseases, cirrhosis, and hepatocellular carcinoma. An important parallel between obesity-related pathology of adipose tissue and liver pertains to the emerging role of macrophages, and growing evidence suggests that Kupffer cells critically contribute to progression of non-alcoholic fatty liver disease. Moreover, a close link between specific immune activation and atherosclerosis has been well established, suggesting that fat can directly trigger immune responses. This review discusses the role of fat as “a matter of disturbance for the immune system” with a focus on hepatic steatosis.

Keywords: Adipocytokine; Adipose tissue; Fat; Immune system; Kupffer cell; Natural killer; Steatosis