Influence of Genetic Obesity, Food Intake and Adrenalectomy in Mice on Selected Trace Element-Dependent Protective Enzymes

Abstract

Experiments were conducted to determine if food intake and adrenalectomy influenced abnormal antioxidant defense mechanisms observed in obese mice. Paired male C57BL/6J mice of two genotypes, obese (ob/ob) and lean (+/?), were fed a nonpurified diet ad libitum or restricted (2.5 g/d) until 3 mo old. Obese mice had larger livers and kidneys but smaller brains than lean mice. Plasma ceruloplasmin activity of obese mice was 240% of that of lean mice. Restricting food intake but not adrenalectomy reduced this difference, but ceruloplasmin activity of obese mice was still 150% of that of restricted-fed lean mice. Glutathione peroxidase (GSH-Px) activity in liver of obese mice was 70% of that in control lean mice; however, in kidney GSH-Px activity was 135% of that in obese mice. Both liver and kidney GSH-Px differences were eliminated by food restriction but not by adrenalectomy. Blood and brain GSH-Px activity was not influenced by the mutation. Liver and kidney copper-zinc superoxide dismutase activity was lower in obese mice than in lean littermates, 30 and 20%, respectively. Food restriction eliminated this difference in liver but not in kidney. Glutathione S-transferase activity using 1-chloro-2,4-dinitrobenzene as substrate was 55% lower in liver (not kidney) of obese mice than in lean mice and this difference was not markedly influenced by food restriction. Obese mice have marked changes in the steady-state activities of a number of protective enzymes that are organ dependent and, in part, due to the hyperphagia associated with this mutation.

Pivotal role of superoxide anion and beneficial effect of antioxidant molecules in murine steatohepatitis

“…Although several groups have found increased extracellular 23 and mitochondrial 24 MnSOD activities, others have observed a decrease in MnSOD caused by altered Mn metabolism in ob/ob mice, 25 in patients with a human leptin gene mutation, 26 and a decrease in both mRNA levels 27 and enzymatic activity 28 of Cu/Zn SOD. These discrepancies are probably related to the age of the experimental animals and suggest that an increase in SOD-like activity occurs early in life of ob/ob mice.…”

Increased glutathione conjugate transport: a possible compensatory protection mechanism against oxidative stress in obesity?

“…[16][17][18] Different results showing decreased, increased or unchanged GST activity in obese subjects and animals when compared with lean subjects and animals were also reported. 5,6,[19][20][21][22] However, the glutathione S-conjugate transport have not been tested for obese subjects. It is also currently unclear whether glutathione levels in various models of obesity are related to a compensatory upregulation of components of the glutathione system or whether there is a continual depletion of glutathione with increasing adiposity.…”

Consumption of Jeju Ground Water Containing Vanadium Components Enhances Hepatic Antioxidant Defense Systems in ob/ob Mice

“…It has been reported that hepatic Cu/Zn SOD, GPx and CAT activities are all reduced in the livers of ob/ob mice in comparison with the livers of wild type mice [16]. In this regard, Jeju ground water S3 and S1 compared with tap water enhanced the protein expression and activity of SOD ( Fig.…”