Glucagon and fasting do not activate peroxisomal fatty acid β-oxidation in rat liver

Abstract

In a study of the endocrine control of peroxisomes, the effects of acute glucagon treatment and fasting on hepatic peroxisomal β-oxidation in rats have been investigated. The activity of the rate-limiting peroxisomal β-oxidation enzyme, fatty acyl-CoA oxidase, was measured to determine whether activation of peroxisomal β-oxidation could account for the increase in total hepatic fatty acid oxidation following acute glucagon exposure. Catalase, a peroxisomal enzyme not directly involved in β-oxidation, was also measured as a control for total peroxisomal activity. No changes with acute glucagon treatment of intact animals were observed with either activity as measured in liver homogenates or partially purified peroxisomal fractions. These observations indicate the lack of acute control by glucagon of peroxisomal function at the level of total enzyme activity. Previous work on the effects of fasting on hepatic fatty acid β-oxidation [ H. Ishii, S. Horie, and T. Suga (1980), J. Biochem., 87, 1855–1858] suggested an enhanced role for the peroxisomal β-oxidation pathway during starvation. It was found that the peroxisomal β-oxidation system, as measured by fatty acyl-CoA oxidase activity, does increase with duration of fast when expressed on a per gram wet weight liver basis. However, when this activity is expressed as total liver capacity, a decline in activity with increasing duration of fast is observed. Furthermore, this decline in peroxisomal capacity parallels the decline in total liver capacity for citrate synthase, a mitochondrial matrix enzyme, and total liver protein. These data indicate that peroxisomal β-oxidation activity is neither stimulated nor even preferentially spared from proteolysis during fasting.