Dietary and Genetic Obesity Promote Liver Inflammation and Tumorigenesis by Enhancing IL-6 and TNF Expression

被引：1437

作者：

Park, Eek Joong ^{[1
,2
]}

Lee, Jun Hee ^{[1
,2
]}

Yu, Guann-Yi ^{[1
,2
]}

He, Guobin ^{[1
,2
]}

Ali, Syed Raza ^{[1
,2
]}

Holzer, Ryan G. ^{[1
,2
]}

Oesterreicher, Christoph H. ^{[1
,2
,3
]}

Takahashi, Hiroyuki ^{[1
,2
]}

Karin, Michael ^{[1
,2
]}

机构：

[1] Univ Calif San Diego, Sch Med, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Sch Med, Dept Pathol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA

来源：

CELL | 2010年 / 140卷 / 02期

基金：

加拿大自然科学与工程研究理事会; 英国惠康基金;

关键词：

INDUCED INSULIN-RESISTANCE; SUBCUTANEOUS ADIPOSE-TISSUE; HEPATOCELLULAR-CARCINOMA; KAPPA-B; CHEMICAL HEPATOCARCINOGENESIS; COMPENSATORY PROLIFERATION; CANCER DEVELOPMENT; INTERLEUKIN-6; CELLS; SERUM;

D O I：

10.1016/j.cell.2009.12.052

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Epidemiological studies indicate that overweight and obesity are associated with increased cancer risk. To study how obesity augments cancer risk and development, we focused on hepatocellular carcinoma (HCC), the common form of liver cancer whose occurrence and progression are the most strongly affected by obesity among all cancers. We now demonstrate that either dietary or genetic obesity is a potent bona fide liver tumor promoter in mice. Obesity-promoted HCC development was dependent on enhanced production of the tumor-promoting cytokines IL-6 and TNF, which cause hepatic inflammation and activation of the oncogenic transcription factor STAT3. The chronic inflammatory response caused by obesity and enhanced production of IL-6 and TNF may also increase the risk of other cancers.

引用

页码：197 / 208

页数：12

共 53 条

[1] IKK-β links inflammation to obesity-induced insulin resistance [J].