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HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



cally normal men (38). In obese individuals the 

 amount of body fat may reach 33 to 40 per cent of 

 body weight. 



During the past twenty years there has been an 

 increasing awareness that adipose tissue is a dynamic 

 organ capable of responding to a variety of stimuli. 

 The experiments of Schoenheimer ( 1 84) and others 

 have shown that depot fat has a definite turnover. Its 

 half-life in the rat has been estimated to be 6 to 8 

 days. In man, turnover of depot fat is much slower, 

 with a half-life of many months, in the presence of 

 adequate caloric intake. When the availability of 

 carbohydrate is reduced, depot fat cells can quickly 

 mobilize free fatty acids which are then bound to 

 albumin and carried in the blood to muscle, liver, 

 and other tissues (52, 84). 



The relationship between the availability of carbo- 

 hydrate and the rate at which fatty acids are mobilized 

 from depot fat is important. Breakdown of glucose 

 through the Embden-Myerhof pathway and the 

 hexosephosphate shunt may provide certain cofactors 

 necessary for fatty acid synthesis (lipogenesis). Insulin 

 promotes entry of glucose into the cell and thereby 

 provides a stimulus for further metabolism of this 

 hexose. Fatty acid synthesis appears to be somehow 

 dependent on the rate of glycolysis. In diabetes melli- 

 tus glycolysis is depressed because of insulin lack; in 

 addition, the rate of fatty acid synthesis is greatly 

 suppressed. At the same time, the rate of hydrolysis 

 of depot fat increases, and the resultant fatty acids 

 are carried into the circulation as free fatty acids. 

 For example, in uncontrolled diabetes, enormous 

 amounts of fat can be mobilized, leading to fatty 

 liver, hypertriglyceridemia, and hyperketonemia. 

 Administration of insulin corrects the situation in a 

 manner that has not been elucidated (203), but prob- 

 ably relates to the ability of insulin to reduce the rate 

 of fatty acid mobilization from adipose tissue. 



Hormonal Influences on Adipose Tissue 



In addition to insulin, several other hormones have 

 been found to influence lipid mobilization. It is em- 

 phasized that hormones do not initiate events within 

 cells, but merely regulate the rate at which some of 

 these events occur. Early studies (148) indicated 

 that when large doses of posterior pituitary extract 

 were injected into rats or rabbits there resulted an 

 accumulation of fat in the liver. Similarly, an increase 

 in liver fat and a decrease of carcass fat of the rat 

 were found following the injection of anterior pitui- 

 tary extract (19). There have been recent reports 



that a posterior pituitary component, a relatively 

 small polypeptide, has a potent mobilizing effect on 

 omental and mesenteric fat in animals and man (185, 

 213). As yet there have been no reports on the influ- 

 ence of this posterior pituitary material on mobiliza- 

 tion of free fatty acids (95). In contrast, it was found 

 (177) that the injection into rabbits of crude extracts 

 of whole or anterior pituitary gland of hogs, sheep, 

 cattle, or man induced visible lipemia which was con- 

 siderably greater than that induced by recognized 

 anterior pituitary hormones. Thus it was suggested 

 that the lipemia-producing principle might be an 

 independent hormone, or that the lipemia was the 

 result of synergistic action of known hormones, al- 

 though the lipemia-producing anterior pituitary 

 component apparently contains negligible or un- 

 detectable amounts of eight known pituitary hormones 

 (178). Also, following injection of this material into 

 rabbits, there was a rapid and enormous (tenfold) 

 increase in free fatty acid levels. This was followed 

 within 12 hours by a twofold to fivefold increase in 

 serum total lipid concentration, including significant 

 increases in the serum levels of triglycerides, choles- 

 terol, and phospholipid. It is difficult to ascertain 

 from these studies whether or not the lipemia that 

 was produced was mediated through another gland, 

 since the recipient animals were neither hypophy- 

 sectomized nor adrenalectomized. The authors have 

 explained their results by postulating that the active 

 principle mobilizes free fatty acids from depot fat. 

 The increase in triglyceride, cholesterol, and phos- 

 pholipid in serum is believed due to increased rate of 

 formation of these substances in the liver, in response 

 to increased hepatic uptake of free fatty acids. 



The possibility that there may be two new factors 

 capable of mobilizing depot fat, one from the anterior 

 and one from the posterior pituitary, deserves further 

 exploration and confirmation by other investigators. 



Of the known pituitary hormones, growth hormone 

 has been shown to possess free fatty acid-mobilizing 

 properties in the intact organism (168). Growth hor- 

 mone action on depot fat (and other sites) appears 

 to depend upon the phylogenetic relationship of the 

 recipient animal to the donor source. For example, 

 beef growth hormone mobilizes fat in cattle and in 

 the rat but not in monkeys or human subjects. Knobil 

 (125) has shown that the administration of growth 

 hormone stimulates, while hypophysectomy inhibits, 

 free fatty acid release from the epidydimal fat body of 

 rats. The manner in which growth hormone promotes 

 free fatty acid release has not been fully elucidated. 



Adrenocorticotropic hormone (ACTH) has been 



