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World J Gastroenterol. Feb 14, 2008; 14(6): 831-844
Published online Feb 14, 2008. doi: 10.3748/wjg.14.831
The blind men ‘see’ the elephant-the many faces of fatty liver disease
Madhusudana Girija Sanal
Madhusudana Girija Sanal, Special Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India
Correspondence to: Dr. Madhusudana Girija Sanal, Senior Fellow Research, Special Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India.
Telephone: +91-11-26717608
Fax: +91-11-26161781
Received: October 9, 2007
Revised: December 24, 2007
Published online: February 14, 2008

Nonalcoholic fatty liver disease (NAFLD) is a group of diseases with excess fat in liver in the absence of a poorly defined limit of alcohol consumption. Most common variety, a universal public health problem, is associated with insulin resistance caused by a host of genetic and epigenetic defects modulated by life style and environmental factors. In fact the term NAFLD is loose to incorporate so many etiologies except alcoholism and few other etiologies, presenting as fat in liver. However as a sign fatty liver is very important in predicting the risk of diabetes, cardiovascular disease, stroke, cirrhosis and cancer. Abnormal fat accumulation can result from several defects in nuclear receptors associated with lipid sensing, synthesis and oxidation like LXR, FXR, SREBP, ChREBP and PPAR; defects in the lipid influx-efflux channels, insulin signaling, proteins involved in fatty acid catabolism, defects in adipose tissue development and function, inappropriate nutrition and finally defects in neural regulatory mechanisms. The progress of the disease is determined by the basic defects which results in fat accumulation, an individual’s immunological response to the accumulated fat and its derivatives and the oxidant stress response. Congregation of unrelated genetic defects under same diagnosis ‘NAFLD’ can result in inefficient patient management. Further studies are required to understand the molecular basis of fatty liver to enable a personalized management of diseases presenting as fatty liver in the absence of alcohol abuse.

Keywords: Nonalcoholic fatty liver disease, Insulin resistance, Lipid homeostasis, Primate evolution, Lipid channels, Lipoprotein, Adipokines, Nuclear receptors, Bile acid metabolism, Personalized medicine