Lifestyle intervention and fatty liver disease: The importance of both disrupting inflammation and reducing visceral fat
Authors: Alexis Elias Malavazos, Giulia Gobbo, Roberta Francesca Zelaschi, Emanuele Cereda
Journal: Hepatology (2009)

We enthusiastically saw the consistent interest given by HEPATOLOGY to the importance of lifestyle interventions in the treatment of both nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Johnson et al.1 have shown that a 4-week aerobic exercise training per se results in a significant reduction in both hepatic lipids and visceral adipose tissue (VAT). Beside this, Promrat et al.2 have demonstrated that a 48-week program based on both physical activity and diet-induced weight loss is able to also improve liver histology of patients with NASH. Indeed, these two trials complement each other in clarifying the role of behavioral treatment in the management of chronic fatty liver disease. Along with this, the importance of combined lifestyle therapy (diet plus physical activity) is strongly supported. The exact mechanisms by which VAT exerts its damaging metabolic consequences remain controversial, but a number of mechanisms have been proposed. It seems likely that both the inflammatory nature of adipose tissue and the amount of abdominal fat accumulation are critical factors in tissue damage. This is what we have previously observed for cardiac dysfunction and morpho-functional abnormalities.3, 4 Thus, both these targets should be addressed in the treatment. Indeed, NASH develops, and potentially progresses to cirrhosis, on a chronic inflammatory background.5, 6 However, liver disease seems to be associated with systemic degenerative disease and metabolic derangements independently of VAT accumulation.7 Adipose tissue is a dynamic organ resulting from the balance of new fat deposition and reabsorption. Several factors are involved in this turnover, such as diet, physical activity, but also inflammation, which is considered per se a major determinant of insulin resistance.8, 9 The portal/fatty acid flux theory suggests that visceral fat, via its unique location and enhanced lipolytic activity, releases toxic free fatty acids, which are delivered in high concentrations directly to the liver. This leads to the accumulation and storage of hepatic fat and the development of hepatic insulin resistance.9 Nonetheless, a study by van der Poorten et al. has recently shown that visceral fat remained an independent predictor of liver inflammation and fibrosis even when measures of insulin resistance, adipokines, and increasing age are considered.10 A 4-week aerobic program can result in a significant reduction of VAT, thus positively affecting the levels of circulating free fatty acids and hepatic lipid accumulation, but appears to be too short a time frame to reduce insulin resistance. Unfortunately, the disruption of inflammatory biomarkers has been not addressed by Johnson et al.1 This is what Promrat et al. were able to demonstrate,2 providing evidence that patients undergoing consistent abdominal adipose tissue loss have improved lobular inflammation and also reduced insulin resistance. Altogether, these results support that both the disruption of inflammation and the reduction of VAT should be targets of therapeutic strategies to reduce local tissue damage. This has been supported for cardiac dysfunction11, 12 and there is some rationale also for treatment of both NAFLD and NASH. However, it must be recognized that it is frequently difficult to keep the patient focused on maintaining changes in lifestyle habits. Alexis Elias Malavazos M.D.*, Giulia Gobbo M.D. , Roberta Francesca Zelaschi M.D.*, Emanuele Cereda M.D., Ph.D. , * Endocrinology Unit, Department of Medical and Surgical Sciences, Istituto di Ricovero e Cura a Carattere Scientifico, (IRCCS) Policlinico San Donato, Università degli Studi di Milano, San Donato Milanese, Italy, Department of Internal Medicine, Department of Medical and Surgical Sciences, IRCCS Policlinico San Donato, Università degli Studi di Milano, San Donato Milanese, Italy, International Center for the Assessment of Nutritional Status (ICANS), Dipartimento di Scienze e Tecnologie Alimentari e Microbiologiche (DISTAM), Università degli Studi di Milano, Milano, Italy.