title: Glucose intolerance and hepatocellular carcinoma: recent findings for old diseases.
abstract: In the last years, an increasing number of evidences on the influence of metabolic syndrome on the occurrence of hepatocellular carcinoma (HCC) have been developed. Type 2 mellitus diabetes (T2MD) has been found to increase the occurrence of primary liver tumors and to define a more aggressive carcinogenetic process. Furthermore, several preclinical and observational studies and a recent meta-analysis have shown that anti-diabetic drugs can modify the risk of HCC development in patients with T2DM. However, despite these evidences, underlying molecular mechanisms linking both pathological conditions have to be completely cleared yet. The study published by Gao et al. has found a possible molecular link between the two conditions, describing the predisposition to T2DM and HCC given by the haploinsufficiency of nuclear receptor coactivator 5 (NCOA5) in murine models. The authors have generated Ncoa5+/- (haploinsufficient) male mice and shown that 94% of male mutant mice developed HCC within 18 months of age, this in contrast with Ncoa5+/+ and Ncoa5+/- female mice. These results suggest that NCOA5 haploinsufficiency is linked to HCC development in male mice. Moreover, mutant male mice showed significantly elevated levels of fasting blood glucose and markedly decreased glucose tolerance and insulin sensitivity compared to Ncoa5+/+ littermates. This well-constructed work sheds light on the molecular link between T2DM and HCC and opens the way to further biological and clinical studies in the field of liver tumor prevention and treatment.
authors.affiliation: Department of Medical Sciences, Gastroenterology Unit, University of Foggia, AOU Ospedali Riuniti, Foggia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Facciorusso
authors.affiliation: Department of Medical Sciences, Gastroenterology Unit, University of Foggia, AOU Ospedali Riuniti, Foggia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Barone
keywords: Nuclear receptor coactivator 5 (NCOA5); diabetes mellitus; hepatocellular carcinoma (HCC); interleukine-6 (IL-6)