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Persistence of Dietary Suppression of 3-Hydroxy-3-Methylglutaryl Coenzyme-A Reductase During Development in Rats^1,2,

Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843

Rat pups suckled by dams fed either a semipurified diet or a commercial rat feed displayed an increase in hepatic 3-hydroxy-3-methyl-glutaryl Coenzyme-A reductase (HMG-CoA reductase) [mevalonate:NADP oxidoreductase (acylating CoA) EC 1.1.1.34] activity reaching a maximum at 4 days after weaning, after which time activity decreased to a minimal plateau. However, the enzyme level was significantly higher in the group consuming commercial feed. Also, the rats fed the semipurified diet reached their adult level (0.17 nmoles mevalonic acid formed/minute/mg protein) at 35 days of age while the level in the commercial rat feed group did not become constant (0.55 nmoles/minute/mg protein) until 60 days of age. Times of diurnal fluctuations were found to be independent of dietary constituents. There were no differences in growth rate, liver size, liver cholesterol or liver lipids due to the diet variables tested. No inhibitor of the enzyme was found in either the microsomal or 105,000 x g supernatant fractions. Insulin gave a normal response in both dietary groups. Rats fed the semipurified diet until 30 or 40 days of age and then fed the commercial rat feed did not maintain the low level of enzyme activity, but soon achieved the high level of the commercial rat feed group. However, those given the semipurified diet until 60 or 80 days of age and then fed the commercial rat feed for 20 days, maintained the low HMG-CoA reductase activity the entire 20 days. These data support the hypothesis that HMG-CoA reductase perturbation by diet manipulation during development may be long lasting or even permanent.

KEY WORDS: • HMG-CoA reductase • development • semipurified diet • stock diet

¹ Supported in part by grants from the National Institutes of Health (AM 06011), The National Dairy Council, National Live Stock and Meat Board, Texas A&M University Research Council and Robert A. Welch Foundation (A-618).

² Presented in part at the meeting of the American Oil Chemists' Society, April 1975.

³ Submitted by GRH in partial fulfillment of the requirements for the degree of Doctor of Philosophy. Present address, Department of Pathology, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27108.

Manuscript received 24 May 1976.