Epinephrine, effect lipolysis

One of the earliest effects found for PGEj was its ability to inhibit epinephrine-induced lipolysis in adipocytes by preventing the accumulation of cAMP ". The ability of PGEj to blunt isoproterenol-induced increases in cAMP in hamster adipocytes was subsequently shown to be reduced in hamsters that had been treated with a crude source of pertussis toxin. More recently, Murayama and Ui demonstrated that pertussis toxin treatment of adipocytes also diminishes the ability of PGEj to cause a GTP-dependent inhibition of adenylate cyclase activity in membranes prepared from these cells associated with this latter effect is a pertussis toxin-dependent, ADP-ribosylation of a protein subunit having the characteristic size (M = 41000) of the subunit of the inhibitory guanine nucleotide regulatory protein N. ... 

Cyclic AMP may also mediate the lipolytic effect of various hormones.99 Numerous lipolytic hormones (ACTH, glucagon, catecdiolamlnes, TSH, and others) Increase tissue levels of cyclic AMP by activation of adenyl cyclase.3-00 This effect Is potentiated by caffeine, an inhibitor of phosphodiesterase.3-80 Insulin, which lowers cyclic AMP levels also inhibits epinephrine induced lipolysis.301,102 Nicotinic acid, another lipolysls inhibitor, virtually obliterates the effects of epinephrine on cyclic AMP levels in isolated fat cells.303 xhe fact that exogenous cyclic A stimulates lipolysls in isolated fat cells301 adds further credence to the hypothesis that hormone induced lipolysls may be mediated by this nucleotide. 

Otfier fiormones accelerate tfie release of free fatty acids from adipose tissue and raise tfie plasma free fatty acid concentration by increasing the rate of lipolysis of the triacylglycerol stores (Figure 25—8). These include epinephrine, norepinephrine, glucagon, adrenocorticotropic hormone (ACTH), a- and P-melanocyte-stimulat-ing hormones (MSH), thyroid-stimulating hormone (TSH), growth hormone (GH), and vasopressin. Many of these activate the hormone-sensitive hpase. For an optimal effect, most of these lipolytic processes require the presence of glucocorticoids and thyroid hormones. These hormones act in a facilitatory or permissive capacity with respect to other lipolytic endocrine factors. 

In fat cells epinephrine stimulation of cyclic AMP accumulation and lipolysis is markedly reduced in hypothyroidism but enhanced in hyperthyroidism (see Ref. 79). Similar effects of altered thyroid status on the response to two other lipolytic hormones, ACTH and glucagon, have been reported suggesting that thyroid hormones regulate similarly either the different receptors of the various lipolytic hormones and/or a common step of the lipolytic pathway [80],... 

A.G. Goldberg and E.G. Ball, Studies on the metabolism of adipose tissue. 18. In vitro effects of insulin, epinephrine and glucagon on lipolysis and glycolysis in pigeon adipose tissue. Comp. Biochem. Physiol., 1965, 16, 367-381. 

S.S. Chernick, P.M. Spooner, M.M. Garrison, and R.O. Scow, Effect of epinephrine and other lipolytic agents on in-tracelluar lipolysis and lipoprotein lipase activity in 3T3-L1 adipocytes, J. Lipid Res., 1986, 27, 286-294. 

In the case of lipolysis, there appears to be a direct correlation between the levels of cyclic AMP achieved and the amount of free fatty acid released, which also strongly implicates the cyclic nucleotide as a hormone mediator in this system as well. Coupled with this fact, it must be recalled that cyclic AMP mimics the effect of epinephrine in liver slices and causes hyperglycemia in various intact animals including humans. ... 

The actions of corticosteroids are interrelated to those of other hormones. In the absence of glucocorticoids, epinephrine and norepinephrine have only minor effects on lipolysis. Administration of a small dose of glucocorticoid, however, markedly potentiates their lipolytic action. Those effects of corticosteroids that involve concerted actions with other hormonal regulators are termed permissive and most likely reflect steroid-induced changes in protein synthesis that, in turn, modify tissue responsiveness to other hormones. 

Fig. 43.6. Effects of epinephrine on fuel metabolism and pancreatic endocrine function. Epinephrine (Epi) stimulates glycogen breakdown in muscle and liver, gluconeogenesis in liver, and lipolysis in adipose tissue. Epinephrine further reinforces these effects because it increases the secretion of glucagon, a hormone that shares many of the same effects as epinephrine. Epi also inhibits insulin release but stimulates glucagon release from the pancreas.

Fig. 43.8. Effects of glucocorticoids (GC) on fuel metabolism. Glucocorticoids stimulate lipolysis in adipose tissue and the release of amino acids from muscle protein. In liver, glucocorticoids stimulate gluconeogenesis and the synthesis of glycogen. The breakdown of liver glycogen is stimulated by epinephrine.

Tremor is a common Pj effect. Blood vessels in the skin have almost exclusively alpha (vasoconstrictor) receptors. Stimulation of renin release is a P, effect. The answer is (C). Epinephrine increases plasma flee fatty acids by activating lipolysis of triglycerides in fat cells. The answer is (E). 

In addition to the study of glycogenolysis, a classical example of the mediation of hormone action by cAMP, other studies include epinephrine stimulation of heart contraction and the induction of lipolysis by a variety of hormones. Epinephrine stimulates cardiac contraction almost instantaneously, the stimulation is inhibited by adrenergic blocking agents, and cAMP mimics the effect of epinephrine. When epinephrine is added to the isolated heart, the levels of cAMP are considerably increased within minutes, and when contraction is blocked, the levels of cAMP are reduced in proportion to the effectiveness of the blocking agent. 

The in vitro lipolytic effects of glucagon and epinephrine were tested in tissues from three avian (goose, duck and owl) and three mammalian species (dog, rat, rabbit). In addition, the effects of insulin and nicotinic acid on the glucagon-induced lipolysis were also tested. The concentrations of the various compounds tested were those known to produce maximal responses in rat epididymal adipose tissue. The experiments provide a comparison of the responses of the adipose tissue from various species with each other, and with that elicited in the rat adipose tissue by hormone concentrations capable of producing the maximal response in the latter tissue (see ref. 36). 

The results of the in vitro experiments were in good agreement with the observations in vivo. Glucagon stimulated lipolysis in all the tissues examined except that of the dog. The greater effects were observed with the tissues of goose and owl. Epinephrine stimulated the lipolytic activity of rat and dog adipose tissues, and had a small effect on the tissues from goose and owl, but no detectable effect on the tissues from rabbit and duck. Insulin had no antilipolytic effect in any of the avian tissues, in agreement with other... 

Lipolytic Effects of Glucagon and Epinephrine and the Effects of Insulin and Nicotinic Acid on Glucagon-induced Lipolysis Adipose tissue in vitro from various mammals and birds ... 

Prigge, W. F. and Grande, F. (1971). Effects of glucagon, epinephrine and insulin on in vitro lipolysis of adipose tissue from mammals and birds. Comp. Biochem. Physiol. 39, B, 69. 

Raising intracellular levels of cyclic AMP stimulates lipolysis in fat pads and isolated cells (4) probably by activating the triglyceride lipase. The nucleotide also stimulates the conversion of phosphorylase b to phosphorylase in muscle and the conversion of the I form of glycogen synthetase to the D form (5, 6). It thus seemed possible that the inhibitory action of insulin on these processes might be mediated by a fall in tissue levels of cyclic AMP. Accordingly we have examined the effect of insulin on cyclic AMP levels in epididymal fat pads incubated with epinephrine and caffeine in the absence of glucose. 

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