Other Wnt Signaling

Supplementary MaterialsSupplementary figures S1CS4

Supplementary MaterialsSupplementary figures S1CS4. degrees of fatty acid synthase PSI-7976 and a largely distinct protein electrophoresis profile from hepatocytes but comparable between different hepatoma lines. We conclude that hepatoma cell lines do not accurately model the hepatocyte for insulin action but may be useful tools to investigate the proteomic changes conferring to hepatocellular carcinoma its peculiar metabolisms. strong class=”kwd-title” Subject terms: Malignancy, Cell biology, Physiology, Diseases, Endocrinology, Gastroenterology, Medical research, Molecular medicine, Oncology, Pathogenesis Introduction Obesity and type-2 diabetes have reached unprecedented proportions and may be the largest pandemic in the history of humanity1. Rabbit Polyclonal to IR (phospho-Thr1375) Furthermore, fatty liver disease is usually a condition closely associated with obesity and insulin resistance, which at advanced stage progresses to cirrhosis and hepatocellular carcinoma, and it was predicted that fatty liver disease will be the first cause for liver transplantation in the near future2. The liver is a major insulin target organ, is the main source of endogenous glucose production, plays a chief role in the control of systemic lipid metabolism, and is central to the link between obesity and type-2 diabetes3C5. Hence, identifying the molecular mechanisms linking obesity to the pathogenesis of hepatic insulin resistance and the progression of fatty liver disease is a major challenge of modern biomedical research. The metabolic function of the liver is highly integrated with other organs and insulin action around the hepatocyte implicates indirect mechanisms involving signals from adipocytes and the brain4,6. PSI-7976 However, recent studies PSI-7976 indicate that direct insulin action around the hepatocyte plays a dominant role in the control of glucose metabolism7,8. A better understanding of the direct insulin action on hepatocyte metabolism in physiological conditions and in obesity is therefore necessary to unravel the link between obesity, insulin resistance, and fatty liver disease. This research field to progress needs a solid cell culture model to investigate and define the molecular mechanisms of insulin action in the hepatocyte and its role in metabolic homeostasis and disease progression. Cultures of hepatoma-derived cell lines display typical morphological features of hepatocytes, express specific hepatocyte markers and therefore can be seen as a practical and ethical alternative to main hepatocyte cell cultures. Indeed, planning of principal hepatocytes requires pets and it is more demanding and labor intensive than immortalized cell lines technically. Furthermore, the option of hepatoma cell lines of individual origin, such as for example HepG2, may be regarded a significant advantage, as human being main hepatocytes have a limited availability at a prohibitive cost. It is therefore not surprising that thousands of studies used hepatoma cell lines, most commonly HepG2 cells, to model hepatocytes in insulin signaling or in rate of metabolism. However, whereas HepG2 proteome was shown to be qualitatively similar to the one of human being main hepatocytes9, principal component analysis of these proteomes could distinguish between these cell-types, indicating significant quantitative variations9,10. Most importantly, insulin actions in hepatoma cell lines continues to be uncharacterized generally. To our understanding, only one latest study has straight compared insulin actions in HepG2 and various other immortalized hepatocyte cell lines, to the main one in principal mouse PSI-7976 hepatocytes, and PSI-7976 many metabolic distinctions between these cell types had been found11. However, the writers cannot measure insulin-induced phosphorylation of AKT and insulin-receptor in HepG2 cells, due to specialized complications most likely, and have not really.