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Reduced Brain Norepinephrine Metabolism in Obese (ob/ob) Mice is Not Normalized by Tyrosine Supplementation^1,2,

Departments of Food Science and Human Nutrition ^* Animal Science, Michigan State University, East Lansing, MI 48824-1224

Five-week-old female lean and obese (ob/ob) mice were fed a 20% protein diet (1.1% tyrosine) or a 20% protein diet supplemented with tyrosine (4% tyrosine). On d 4 of supplementation, brain norepinephrine (NE) synthesis rate and brain efflux of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), a major metabolite of NE in mouse brain, were measured after administration of the monoamine oxidase inhibitor pargyline. Control obese mice had a lower rate of NE synthesis and a lower MHPG efflux than lean controls. Tyrosine supplementation elevated brain tyrosine concentration twofold, but had no effect on NE synthesis rate or MHPG efflux in either group. Likewise, tyrosine supplementation for up to 1 mo had no effect on food intake, oxygen consumption or body weight in obese mice and only a transient effect in lean mice, in which oxygen consumption was higher on d 2 and 3 and food intake was higher on d 3 and 4 compared with nonsupplemented lean mice. We conclude that tyrosine availability is not a limiting factor in the reduced brain noradrenergic activity of obese mice.

KEY WORDS: • tyrosine • brain norepinephrine turnover • obese (ob/ob) mice

¹ Supported by the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases of the NIH, AM 15847. Michigan State University Agricultural Experiment Station journal article 11,565.

² Presented in part at Fourth International Congress on Obesity, New York, NY, October 8, 1983, and at 68th Annual Meeting of Federation of American Societies for Experimental Biology St. Louis, MO, April 3, 1984.

³ Supported by a postdoctoral fellowship from National Health Research and Development Program, Health and Welfare Canada.

⁴ Present address: Department of Foods and Nutrition, University of Alberta, Edmonton, Alberta, Canada T6G 2M8.

⁵ To whom requests for reprints should be sent.

Manuscript received 4 April 1985. Revision accepted 30 October 1985.