Fatty acid biosynthesis and RNA function in fasting, aging and diabetes

1.1.Acetate incorporation into the total lipid of adipose tissue and mono-unsaturated fatty acid synthesis is markedly depressed in fasted rats. These observations have been associated with a depression in RNA synthesis. Refeeding a fasted animal leads to return of RNA synthesis to normal within 4 hr which precedes the increase of fatty acid biosynthesis.2.2.During aging, in the rat, there is a progressive decline in saturated and monounsaturated fatty acid synthesis in adipose tissue. These biosynthetic changes can be restored toward the pattern of young animals either by the feeding of a fat-free diet or by the administration of insulin. The RNA concentration of the adipose tissue from old rats is significantly lower than in young rats, but the specific activity of the RNA species isolated from adipose tissue after incubation with uridine-5-T is significantly greater in the old than in the young. This finding may be due to a decrease in the size of the precursor nucleotide pool.3.3.In alloxan diabetes, there is a decrease in acetate incorporation into total lipid and a defect in microsomal monoenoic fatty acid synthesis. These defects are repaired by the administration of insulin after a lag period of 6–12 hr. The coincident administration of actinomycin-D with insulin prevents the restoration of lipid biosynthetic activity but does not modify the hypoglycemic action of the hormone. These observations indicate that insulin stimulates the renewal of cellular RNA necessary for the synthesis of specific anabolic enzymes. The action of insulin on increasing the transport of glucose across cell membranes is not dependent on new enzyme synthesis.Following a single injection of insulin, the restoration of lipid biosynthesis to normal is maintained for more than 24 hr. Evidence has been obtained which indicates that the informational RNA-ribosome complex formed under the influence of insulin is more stable than the enzyme(s) synthesized on the template.4.4.From the direct and indirect evidence relating RNA function to fatty acid synthesis, it is proposed that the fundamental disturbances in fasting, aging, and diabetes affect RNA synthesis primarily and the enzymatic failures are secondary to this.