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Hepatic hyperplasia in noncirrhotic fatty livers: is obesity-related hepatic steatosis a premalignant condition?

Publication ,  Journal Article
Yang, S; Lin, HZ; Hwang, J; Chacko, VP; Diehl, AM
Published in: Cancer Res
July 1, 2001

It is not known whether obesity increases the risk for hepatocellular carcinoma (HCC) simply because it promotes cirrhosis, a general risk factor for HCC, or via some other mechanism that operates independently of cirrhosis. If the latter occurs, then hepatocyte hyperplasia, an early event during the neoplastic process, might begin before liver cirrhosis develops. Genetically obese, leptin-deficient ob/ob mice are models for nonalcoholic fatty liver disease (NAFLD), a type of liver disease that is strongly associated with obesity and type 2 diabetes. Similar to obese, diabetic patients, ob/ob mice have an increased incidence of HCC. However, unlike humans with NAFLD, they rarely, if ever, develop cirrhosis spontaneously. To determine whether the noncirrhotic livers of ob/ob mice with NAFLD exhibit hepatocyte hyperplasia, parameters of proliferation and apoptosis were compared in adult ob/ob mice and their healthy litter mates. Adult ob/ob mice have an increase in liver mass relative to body mass. This hepatomegaly cannot be explained solely by lipid accumulation and is accompanied by significant increases in hepatocyte proliferative activity (as evidenced by increased Erk activation, cell-cycle related gene expression, bromodeoxyuridine incorporation, and hepatic DNA content) with concomitant inhibition of hepatocyte apoptosis (as evidenced by decreased numbers of apoptotic hepatocytes, induction of several antiapoptotic mechanisms, and decreased activation of procaspase 3). Thus, liver hyperplasia is evident at the earliest stage of NAFLD in ob/ob mice, which supports the concept that obesity-related metabolic abnormalities, rather than cirrhosis, initiate the hepatic neoplastic process during obesity.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

July 1, 2001

Volume

61

Issue

13

Start / End Page

5016 / 5023

Location

United States

Related Subject Headings

  • Precancerous Conditions
  • Oncology & Carcinogenesis
  • Obesity
  • Mice, Obese
  • Mice, Inbred C57BL
  • Mice
  • MAP Kinase Signaling System
  • Liver Neoplasms, Experimental
  • Liver
  • Hyperplasia
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yang, S., Lin, H. Z., Hwang, J., Chacko, V. P., & Diehl, A. M. (2001). Hepatic hyperplasia in noncirrhotic fatty livers: is obesity-related hepatic steatosis a premalignant condition? Cancer Res, 61(13), 5016–5023.
Yang, S., H. Z. Lin, J. Hwang, V. P. Chacko, and A. M. Diehl. “Hepatic hyperplasia in noncirrhotic fatty livers: is obesity-related hepatic steatosis a premalignant condition?Cancer Res 61, no. 13 (July 1, 2001): 5016–23.
Yang S, Lin HZ, Hwang J, Chacko VP, Diehl AM. Hepatic hyperplasia in noncirrhotic fatty livers: is obesity-related hepatic steatosis a premalignant condition? Cancer Res. 2001 Jul 1;61(13):5016–23.
Yang, S., et al. “Hepatic hyperplasia in noncirrhotic fatty livers: is obesity-related hepatic steatosis a premalignant condition?Cancer Res, vol. 61, no. 13, July 2001, pp. 5016–23.
Yang S, Lin HZ, Hwang J, Chacko VP, Diehl AM. Hepatic hyperplasia in noncirrhotic fatty livers: is obesity-related hepatic steatosis a premalignant condition? Cancer Res. 2001 Jul 1;61(13):5016–5023.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

July 1, 2001

Volume

61

Issue

13

Start / End Page

5016 / 5023

Location

United States

Related Subject Headings

  • Precancerous Conditions
  • Oncology & Carcinogenesis
  • Obesity
  • Mice, Obese
  • Mice, Inbred C57BL
  • Mice
  • MAP Kinase Signaling System
  • Liver Neoplasms, Experimental
  • Liver
  • Hyperplasia