transported out of the peroxisome where oxidation is com-This study investigates the effects of either a high-fat pleted by the mitochondrial b-oxidation system. 3 The findings diet or endotoxin on peroxisome metabolism as assessed of Osmundsen et al. have suggested that: ''Induction of perby measuring catalase activity, catalase mass, and peroxisomal b-oxidation can be regarded as a detoxification oxisomal b-oxidation. Three mouse strains C3H/HeJ, pathway, induced when the organism is faced with a high BALB/c, and C57BL/6J were fed either a low-fat or a influx of fatty acids which are poorly oxidized by mitochonhigh-fat diet and injected intraperitoneally with 1 mg dria.'' 3 Escherichia coli lipopolysaccharide. These parameters Catabolism of fatty acids by the peroxisomal b-oxidation were not different in C3H/HeJ mice fed a high-fat diet pathway results in chain shortening and the production of compared with controls fed a low-fat diet. Total liver hydrogen peroxide. Catalase is present in high concentration catalase activity and peroxisomal b-oxidation were in peroxisomes and scavenges the reactive and potentially higher in BALB/c mice fed high-fat diet compared with harmful H 2 O 2 , producing O 2 and H 2 O. In vivo studies show low-fat controls. Total liver catalase activity, catalase that peroxisomal b-oxidation increases when rats are fed mass and peroxisomal b-oxidation increased to the high-fat diets. 5-7 We have observed that hepatic peroxisomes, greatest extent in C57BL/6J mice fed a high-fat diet. Enin three strains of mice commonly used as a model of atherodotoxin treatment did not alter any of the parameters sclerosis, showed different levels of response to a high-fat in mice fed a low-fat diet. Among mice fed a high-fat diet, diet (DeLamatre, et al., unpublished observations). Peroxiendotoxin did not affect hepatic catalase or peroxisomal somal b-oxidation did not change in response to a high-fat b-oxidation in the C3H/HeJ mice, decreased catalase acdiet in C3H/HeJ mice, increased in BALB/c mice (Hilltop tivity in BALB/c mice (28%), and greatly decreased both
Labs, Scottdake, PA) and increased to the greatest extent catalase (66%) and peroxisomal b-oxidation (69%) in in C57BL/6J mice (Jackson Laboratories, Bar Harbor, ME).
C57BL/6J mice. The decrease in catalase activity in
Higher levels of peroxisomal b-oxidation activity should in-C57BL/6J mice was apparently because of an inactivacrease H 2 O 2 production. Because H 2 O 2 is thought to be a tion of the enzyme as determined by the activity/mass mediator of endotoxemia, 8,9 the level of peroxisomal b-oxidaratio. Thus, endotoxin is showed to inhibit both catalase tion activity may influence the response to endotoxin. Cataand peroxisomal b-oxidation in mice and the sensitivity lase is probably important in this response because of its to endotoxin is greatest in C57BL/6J mice fed a high-fat critical role in scavenging H 2 O 2 . Thus, the peroxisome may diet. (HEPATOLOGY 1996;24:592-595.)
influence the response of the animal to endotoxin. In this report, we compare the endotoxin response of hepatic peroxi-Peroxisomes contain a diverse array of oxidative enzymes, somes in three mouse strains fed either a low-fat or a highincluding a b-oxidation system that is separate from the mitofat diet. chondrial b-oxidation pathway. 1 Peroxisomes have been shown to be important in the oxidation of long-chain (Β’16
Methods
carbon) fatty acids and some unusual fatty acids including the side chain of cholesterol, dicarboxylic fatty acids, certain Seven-week-old female C3H/HeJ, C57BL/6J (Jackson Laboradrugs, and xenobiotics. 2 Trans fatty acids are apparently oxitories) and BALB/c (Hilltop Labs) mice were fed either a low-fat dized in the peroxisomes because partially hydrogenated oils rodent chow (4% wt/wt; #5012, Purina, Richmond, IN) or a standard are more effective inducers of peroxisomes than their unproatherogenic, high-fat diet (15% wt/wt; polyunsaturated to saturated cessed forms. 3 Livers from vitamin E-deficient rats have an ratio, 0.7; ICN, Cleveland, OH) for 8 weeks ad libitum. 10 The fatty acid composition of the diet was as follows: 16:0, 20.7%; 16:1, 0.3%; increased peroxisomal b-oxidation activity that correlates