Essential fatty acids, diabetes, and cholesterol

520

LETTERS

Essential

Fatty

TO

Acids,

THE

EDITORS

Diabetes,

and

Cholesterol

Although the essentiality of certain unsaturated fatty acids has been recognized since the classical findings of Burr and Burr (l), the biochemical role of these essential fatty acids (EFA) has only recently received attention. In an attempt to discover the specific role for these substances in living systems, several different metabolic approaches have been carried out using the rat. One approach, reported briefly here, relates EFA, diabetes, and cholesterol. Because of the accelerated mobilization and catabolism of fats associated with diabetes, it seemed that the diabetic animal might deplete its EFA reserves faster. Reports of hypercholesterolemia and lipemia in diabetics prompted us to study the influence of dietary cholesterol upon alloxan-diabetic animals. Male weanling rats were placed on an EFA-deficient diet (a), and rendered diabetic 4 days later by injection of alloxan, 16 mg./lOO g. b.w. after prior fasting. The rats were then placed on the experimental diets. A second dose of alloxan was administered 2 weeks later to ensure diabetes. The following results were obtained:

Alloxan-Diabetic Group

Number rats

1 2 3 4

4 6 7 7

of

Cornoil ester

1% 0 1% 0

Rats

Cholesterol

0 0 1% 1%

31.day weight change k.)

31.day dermal store(2)

51 32 51 37

0.8 5.1 1.4 5.2

These results support the assumption that the diabetic rat is more rapidly depleted of his EFA, because both growth differences and dermal symptoms are those usually found in EFA deficient rats only after 3 months depletion (3). Dietary cholesterol does not significantly influence the development of the deficiency in the diabetic animal. The influence of cholesterol in transporting EFA has been suggested by Kelsey and Longenecker (4) and by Alfin-Slayter et al. (5). A study of the influence of dietary cholesterol on (nondiabetic) EFA-deficient rats produced striking results. We have repeatedly obtained an EFA deficiency syndrome, judged by growth and dermal symptoms, within periods of 2 weeks to 1 month by the addition of 1% cholesterol to the fat-deficient diet. Comparable EFA deficiency symptoms are observed only after 3 months on fat-free diets without cholesterol. EFA deficiency in the diabetic animal and EFA deficiency intensified by dietary cholesterol in the nondiabetic animal are similar. It is possible that both syndromes are reflections of the same phenomenon. Accelerated transport of EFA due either to endogenous hypercholesterolemia in the diabetic animal, or to exogenous hypercholesterolemia in the nondiabetic animal, leads to the more rapid depletion of body stores of EFA. Because of the evident relationships of cholesterol and diabetes to atherosclerosis, it might be suggested that atherosclerosis is an expression of EFA deficiency or its faulty metabolism.

LETTERS

TO

THE

521

EDITORS

REFERENCES

1. BURR, 2.

3. 4. 5.

G. O., AND BURR, M. M., J. Biol. Chem. 82,345 (1929). HOLMAN, R. T., AND ENER, S., J. Nutrition 63, 461 (1954). HOLMAN, R. T., in “The Vitamins,” (W. H. Sebrell, J. and R. S. Harris, eds.) Vol. II, p. 267. Academic Press, New York 1954. KELSEY, F. E., AND LONGENECKER, H. E., J. Biol. Chem. 139,727 (1941). ALFIN~LAYTER, R. B., AFTERGOOD, L., WELLS, H. F., AND DEUEL, H. J., JR., Arch. Biochem. and Biophys. 62, 180 (1954).

The Hormel University

Austin, Received

J. J. PEIFER RALPH T. HOLMAS

Institute, of Minnesota,

Minnesota May

13, 1965

Magnesium

Protection

in Mechanical

Trauma

While investigating nucleotide alterations following tourniquet trauma in rats (l), the question arose as to whether the almost complete destruction of ATP in the occluded limbs may play an important part in the development of shock upon tourniquet release. If the destruction of ATP is a causative factor, any means by which ATP decomposition can be inhibited or slowed down during the application of tourniquets would be evidenced by a decrease in mortality. Since DuBois, Albaum, and Potter (2) found that in animals subjected to magnesium anesthesia the available ATP content of the muscle and brain is higher than that in animals anesthetized with ether, it was decided to treat the rats with magnesium sulfate in conjunction with tourniquet shock. Our standard tourniquet-shocked rat was produced by the application of rubber band, arterial tourniquets to both hind legs of a 200-300 g. Sprague-Dawley rat under light ether anesthesia. The incisor teeth were clipped to prevent self-mutilation and the tourniquets were maintained for 4 hr. Magnesium-treated rats were injected at lo-min. intervals intraperitoneally with three 100 mg. doses of MgS01.7Hz0, contained in 1 ml. of H20. Ten minut,es after the third injection, the tourniquets were applied as above. ATP in the hind limbs was determined by ion exchange chromatography as previously reported (1). The concentration of ATP in the occluded leg muscle of rats treated prior to tourniquet with magnesium sulfate (Table I) is higher than that of untreated rats, indicating the possibility of an inhibition of the nucleotide breakdown. An examination of Table II indicates that the treatment of rats with magnesium sulfate prior to the tourniquet application significantly decreases the mortality rate. Further investigation is under way to try to correlate the ATP content and electrolyte levels of the occIuded muscIe at the time of tourniquet release and the survival of the animals.