36 II. BIOSYNTHESIS 



non-ruminants (mouse, rat, and rabbit), as judged by its influence on the 

 R.Q. Glucose is required in the medium. Acetate is also converted to 

 fat in the presence of glucose. The threshold concentration of insulin re- 

 quired to initiate this reaction was found to be only approximately 0.1 ng. 

 (0.0022 I.U./ml). 



The action of insulin in effecting fat synthesis is also a function of species. 

 Thus, although insulin can stimulate fat synthesis in mammary tissue of 

 the non-ruminants, it is unable to effect a similar augmentation in udder 

 slices of ruminants such as sheep. The effect of species on lipogenesis, as 

 demonstrated by the use of the R.Q., has been confirmed by the employ- 

 ment of labeled substrates. Thus, Balmain and co-workers''" reported 

 that increased fat synthesis occurred with mammary slices of the rat 

 when insulin was added to the medium, as judged from the C^*-fatty 

 acids synthesized after C^^-carboxyl-labeled acetate and unlabeled glucose, 

 respectively, were used. The effect of insulin in fat formation was con- 

 firmed later by the use of tritium in the medium. ^^' Finally, it was like- 

 wise found by the use of isotope experiments that fat synthesis from ace- 

 tate or from glucose and acetate in the udder of sheep is uninfluenced by 

 insulin; this confirms the R.Q. studies. Insulin, by itself, was shown to be 

 inactive in stimulating lipogenesis in mammary tissue. 



b. The Effect of the Hormones of the Anterior Lobe of the Pituitary. 

 Brady, Lukens, and Gurin'^° are of the opinion that neither insulin nor the 

 anterior pituitary hormones are required for the synthesis of fatty acids 

 from acetate by the liver. It is suggested that the pituitary secretes a 

 principle which inhibits lipogenesis either directly, or indirectly through 

 the mediation of some other endocrine organ. Insulin appears to act as 

 an antagonist to an inhibitory substance of this nature. Normal fatty 

 acid syiithesis requires an appropriate balance between the insulin and 

 the hypophyseal activity. 



The results of a number of investigations are readily understood if one 

 accepts the premise that fat synthesis depends upon the balance between 

 insulin and the anterior pituitary hormone. Thus, Brady et al.^^^ noted 

 that pancreatectomy inhibited lipogenesis, while hypophysectomy and 

 adrenalectomy produced an augmented fat synthesis. Hepatic lipogenesis 

 proceeded at a normal rate in liver slices from depancreatized-hypophy- 

 sectomized cats; the rate was variable in hepatic tissue from depancrea- 

 tized-adrenalectomized animals. It is claimed'^^ that growth hormone 

 prevents lipogenesis in Houssay cats (depancreatized and hypophysec- 



iM R. O. Brady, F. D. W. Lukens, and S. Gurin, Science, 113, 413-415 (1951). 



1" R. O. Brady, F. D. W. Lukens, and S. Gurin, /. Biol. Chem., 193, 459-464 (1951). 



