title: Could metabolic syndrome lead to hepatocarcinoma via non-alcoholic fatty liver disease?
abstract: It was estimated that from 2002 to 2008 the risk of developing cancer increased a quarter-fold in men and two-fold in women due to excessive BMI. Obesity, metabolic syndrome and type 2 diabetes mellitus are strictly related and are key pathogenetic factors of non-alcoholic fatty liver disease (NAFLD), the most frequent liver disease worldwide. The most important consequence of the "metabolic epidemics" is the probable rise in the incidence of hepatocarcinoma (HCC), and NAFLD is the major causative factor. Adipose tissue is not merely a storage organ where lipids are preserved as an energy source. It is an active organ with important endocrine, paracrine, and autocrine actions in addition to immune functions. Adipocytes produce a wide range of hormones, cytokines, and growth factors that can act locally in the adipose tissue microenvironment and systemically. In this article, the main roles of insulin growth factor (IGF)-1 and IGF-2 are discussed. The role of IGF-2 is not only confined to HCC, but it may also act in early hepato-carcinogenesis, as pre-neoplastic lesions express IGF-2 mRNA. IGF-1 and IGF-2 interact with specific receptors (IGF-1R and IGF-2R). IGF-1R is over-expressed in in vitro and in animal models of HCC and it was demonstrated that IGF ligands exerted their effects on HCC cells through IGF-1R and that it was involved in the degeneration of pre-neoplastic lesions via an increase in their mitotic activity. Both IGF-2R and TGF β, a growth inhibitor, levels are reduced in human HCC compared with adjacent normal liver tissues. Another key mechanism involves peroxisome proliferator-activated receptor (PPAR)γ. In in vitro studies, PPARγ inhibited various carcinomas including HCC, most probably by regulating apoptosis via the p21, p53 and p27 pathways. Finally, as a clinical consequence, to improve survival, efforts to achieve a "healthier diet" should be promoted by physicians and politicians.
authors: Antonella Scalera, Giovanni Tarantino, Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, 80131 Naples, Italy.
authors: Antonella
authors: A
authors: Scalera
authors: Antonella Scalera, Giovanni Tarantino, Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, 80131 Naples, Italy.
authors: Giovanni
authors: G
authors: Tarantino
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000378:metabolism / Q000517:prevention & control; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D004032:Diet / Q000009:adverse effects; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008019:Life Style; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000378:metabolism / Q000517:prevention & control; D024821:Metabolic Syndrome / Q000453:epidemiology* / Q000378:metabolism / Q000517:prevention & control; D065626:Non-alcoholic Fatty Liver Disease / Q000453:epidemiology* / Q000378:metabolism / Q000517:prevention & control; D047495:PPAR gamma / Q000378:metabolism; D012307:Risk Factors; D040242:Risk Reduction Behavior; D015398:Signal Transduction
chemical_list: D054392:Adipokines; D047495:PPAR gamma; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II
keywords: Adipokines; Hepatocarcinoma; Insulin growth factor; Non-alcoholic fatty liver disease; Peroxisome proliferator-activated receptor γ