Monoamine oxidase, catechol-O-methyltransferase, and norepinephrine levels in mice with the hereditary obese-hyperglycemic syndrome.

Abstract

There is some evidence that there are abnormalities in catecholamine metabolism in patients with obesity and diabetes mellitus. In this study we determined the tissue levels of catecholamine-metabolizing enzymes (monoamine oxidase [MAO] and catechol-O-methyltransferase [COMT]) and norepinephrine (NE) in mice with the hereditary obese-hyperglycemic syndrome (ob/ob mice). The ob/ob mice have greater MAO activity in their kidneys (+ 43 per cent), testes (+ 51 per cent), and white adipose tissue (+ 87 per cent) than their normal-weight Httermates. There is no difference in MAO activity of pancreas, liver, brain, brown fat, heart, and islets of Langerhans in ob/ob and normal mice. The ob/ob mice have less COMT activity in their liver (−39 per cent) than normal mice. There is no difference in COMT activity in the kidney, testis, pancreas, and brain between ob/ob and normal mice. The Michaelis constant of kidney MAO for the tryptamine substrate is similar in normal and obese mice, suggesting that the increased MAO activity is due to a greater amount of tissue MAO rather than an altered affinity of MAO for the tryptamine substrate. The ob/ob mice have a persistent elevation in MAO activity despite eugiycemia (older mice) and a reduction in weight (caloric restriction), suggesting that the elevated MAO activity in ob/ob mice is a primary rather than a secondary disturbance. The total NE content of kidney, white fat, and brown fat is similar in ob/ob and normal mice. The islet NE content is less than 3 pg. per islet in ob/ob and normal mice.