found to be very active in inducing free fatty acid 

 release from adipose tissue in vitro (43, 61). However, 

 such an effect is not readily demonstrated in vivo. 

 The reason for this discrepancy is not clear, although 

 a difference in species response to ACTH with respect 

 to free fatty acid release has been offered as a possible 

 explanation (61 ). 



The role of thyroid in the metabolism of depot fat 

 also is under study. The lipolytic response of adipose 

 tissue from thyroidectomized animals (which had 

 been suppressed) was made normal by restoration of 

 the euthyroid state, while hyperthyroidism accen- 

 tuated such a response (170). Moreover, it has been 

 shown that the treatment of hypothyroid patients 

 with thyroid restored to normal their free fatty acid 

 response to growth hormone (167). Thus the thyroid 

 appears to play a permissive role in fat mobilization, 

 potentiating the action of certain lipolytic agents. 



The autonomic nervous system was long suspected 

 of playing an important part in the metabolism of 

 depot fat (24, 207). Early observations on the auto- 

 nomic innervation of adipose tissue have received 

 support from more recent studies on the action of epi- 

 nephrine and norepinephrine on depot fat. Subcu- 

 taneous administration or intravenous infusion of 

 epinephrine and norepinephrine induced significant 

 elevations of free fatty acids in the plasma of intact 

 animals and human subjects (52, 80, 84). Moreover, 

 adipose tissue in vitro has been found to be exquisitely 

 sensitive to epinephrine and norepinephrine in terms 

 of free fatty acid release (27, 61, 137, 210). It has 

 been shown that adipose tissue liberates glycerol in 

 response to epinephrine and norepinephrine (61, 137) 

 suggesting that the mode of action of these hormones 

 on adipose tissue involves hydrolysis of triglyceride. 

 An epinephrine-sensitive lipolytic system has been 

 reported in adipose tissue (172). The influence on 

 depot fat of chronic administration of epinephrine 

 and norepinephrine, as well as other sympathomi- 

 metic agents, remains unknown. 



The various factors influencing lipogenesis and 

 mobilization of fat from adipose tissue are summarized 

 in figure 3. 



In view of the importance of the subject of lipid 

 mobilization and lipogenesis in the scheme of knowl- 

 edge about metabolism, it is surprising that investiga- 

 tion in this area has lagged until recently. Conceiv- 

 ably, as knowledge of the subject increases, the 

 physician will be the beneficiary of valuable adjuncts 

 in the treatment of lipid disorders. Thus, adipose 

 tissue, once thought to be a relatively inert storehouse 

 of dense calories, has been found capable of partaking 



Glucose 



Insulin 



LIPID METABOLISM 



Fatty Acid - Albumin 



'I 75 



CO, 



-ACETYL CoA 



GLUCOSE - P 

 x- Glycer 



FATTY ACID -CoA 



Glycerol 



Fat 

 Droplet 



Chylomicron 



fig. 3. A scheme of lipogenesis and lipolysis in the adipose 

 cell. Free fatty acid release is promoted by: glucose lack, 

 starvation, insulin lack, epinephrine, glucagon (in vitro), 

 norepinephrine, growth hormone, ACTH (in vitro), thyroid 

 hormone (? permissive), and certain extracts from anterior 

 and posterior pituitary glands. 



actively and rapidly in a number of metabolic proc- 

 esses and of responding to a variety of humoral and 

 autonomic stimuli. 



THE SERUM LIPIDS 



The serum lipids can be broadly classified under 

 two major headings: the lipoproteins and the free 

 (or nonesterified) fatty acids (FFA or NEFA). The 

 lipoproteins represent a whole spectrum of lipid mole- 

 cules containing varying proportions of phospholipid, 

 cholesterol (free and esterified), protein (polypeptide), 

 glyceride, and water. The lipoproteins have been 

 classified according to their behavior in the ultra- 

 centrifuge, by their migratory behavior during elec- 

 trophoresis, by their principal X-terminal amino 

 acid residue, by their solubility characteristics, and 

 other ways (155, 194). The density of the lipoprotein 

 molecule is largely a function of the proportion of 

 lipid contained within it; hence, the more "obese" 

 the molecule, the lower its density. 



The lipoprotein species with the lowest density are 

 the chylomicrons; the remaining species can be further 

 divided according to their electrophoretic migration 

 with alpha globulins and beta globulins into two 

 groups, the lower density (beta) lipoproteins and the 

 higher density (alpha) lipoproteins. 



The free fatty acids are present in a relatively low 

 concentration in plasma under basal conditions 

 (approximately 0.2 to 12.0 meq liter). However, 

 they appear to have a rapid turnover rate. They 

 travel in the circulation bound to albumin and per- 



