Obesity, oxidative stress, and
inflammation are risk factors for
hepatocellular carcinoma (HCC). We examined, in mice, the effects of Krüppel-like
factor 9 (KLF9) knockout on: adiposity, hepatic and systemic oxidative stress, and hepatic expression of pro-inflammatory and NOX/DUOX family genes, in a high-fat diet (HFD) context. Male and female Klf9+/+ (wild type, WT) and Klf9-/- (knockout, KO) mice were fed HFD (beginning at age 35 days) for 12 weeks, after which liver and adipose tissues were obtained, and serum
adiponectin and
leptin levels, liver fat content, and markers of oxidative stress evaluated. Klf9-/- mice of either sex did not exhibit significant alterations in
weight gain, adipocyte size,
adipokine levels, or liver fat content when compared to WT counterparts. However, Klf9-/- mice of both sexes had increased liver weight/size (
hepatomegaly). This was accompanied by increased hepatic oxidative stress as indicated by decreased GSH/
GSSG ratio and increased
homocysteine,
3-nitrotyrosine,
3-chlorotyrosine, and 4HNE content. Decreased GSH to
GSSG ratio and a trend toward increased
homocysteine levels were observed in the corresponding Klf9-/- mouse serum. Gene expression analysis showed a heightened pro-inflammatory state in livers from Klf9-/- mice. KLF9 suppresses hepatic oxidative stress and
inflammation, thus identifying potential mechanisms for KLF9 suppression of HCC and perhaps
cancers of other tissues.