Adipose tissue lipolytic hormones

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). 

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. 

Figure 25-8. Control of adipose tissue lipolysis. (TSH, thyroid-stimulating hormone FFA, free fatty acids.) Note the cascade sequence of reactions affording amplification at each step. The lipolytic stimulus is "switched off" by removal of the stimulating hormone the action of lipase phosphatase the inhibition of the lipase and adenylyl cyclase by high concentrations of FFA the inhibition of adenylyl cyclase by adenosine and the removal of cAMP by the action of phosphodiesterase. ACTFI,TSFI, and glucagon may not activate adenylyl cyclase in vivo, since the concentration of each hormone required in vitro is much higher than is found in the circulation. Positive ( ) and negative ( ) regulatory effects are represented by broken lines and substrate flow by solid lines.

Hormones can modify the concentration of precursors, particularly the lipolytic hormones (growth hormone, glucagon, adrenaline) and cortisol. The lipolytic hormones stimulate lipolysis in adipose tissue so that they increase glycerol release and the glycerol is then available for gluconeogenesis. Cortisol increases protein degradation in muscle, which increases the release of amino acids (especially glutamine and alanine) from muscle (Chapter 18). 

The mobilization of the depot fat of adipose tissues requires hydrolysis of the triglycerides. Adrenalin or other lipolytic hormones trigger a... 

HSL activity was first identified in 1964 as an epinephrine-sensitive lipolytic activity in adipose tissue. It was named according to its property of being activated by hormones such as catecholamines, ACTH, and glucagon [29]. In 1981 the isolation of a relatively pure and biologically active HSL from rat adipocytes was reported [30]. The first cDNA clones were isolated for both rat and human HSL in 1988 [31] and the gene sequence for human HSL was elucidated in 1993 [32]. 

TAG mobihzation by hpolysis as a strictly regulated process has been known since the early 1960s, when it was estabhshed that fast-acting hormones such as ACTH and epinephrine increased hpolysis [219, 220], and that insuhn counteracted this activation [221-223]. It was soon recognized that cAMP was involved in the regulation of the catecholamine-sensitive lipolytic activity in adipose tissue... 

Buyse, J., Decuypere, E., Leenstra, F.R. Scanes, C.G. (1992). Abdominal adipose tissue from broiler chickens selected for body weight or for food efficiency differ in in vitro lipolytic sensitivity to glucagon and to chicken growth hormone, but not to dibutyryl cAMP. Br. Poult. Sci., 33, 1069-75. 

Hormone-sensitive lipase tissue activity is stimulated by adrenaline (epinephrine), glucagon, ACTH (corticotropin), TSH (thyrotropin) and serotonin (Jensen, 1971). These hormones are presumed to exert their effects on adipose tissue by stimulating adenylate cyclase. Certainly, an increased formation of cAMP (cyclic AMP) is brought about by lipolytic hormones and cAMP has been shown to stimulate lipase activity in cell-free preparations (cf. O Doherty, 1978). 

Effect on Lipid Metabolism. Our knowledge of the effect of cortisone on lipid metabolism is still fragmentary. Interpretation of the results is complicated by the fact that the effect of the hormone seems to vary depending upon the source of the adipose tissue. Adrenalectomy stimulates and corticoid injections decrease lipogenesis in the adipose tissue of the mesentery. The decreased lipogenesis induced by corticosteroids is accompanied by release of free fatty acids. When corticosterone and hydrocortisone are added to epididymal adipose tissue incubated in vitro, the hormones fail to stimulate lipogenesis from [ " Cjpyruvate, but they accelerate fatty acid release, and the lipolytic effect is completetly blocked by actinomycin D. Consequently, one effect of glucocorticoids on some of the adipose tissues seems to be to accentuate lipid catabolism. 

Another hormonal interrelationship exists between epinephrine and thyroid hormone. Tissues of rats treated with propylthiouracyl released very little fatty acids and did not respond to the addition of epinephrine. Conversely, in tissues of rats treated with triiodothyronine both basal release and response to epinephrine were exaggerated (Debons and Schwartz 1961 Deykin and Vaughan 1963). Release of free fatty acids by adipose tissue from rats treated with triiodothyronine or propylthiouracyl showed that the greater accumulation of fatty acids in the medium of tissues from triiodothyronine treated rats was at the expense of preformed tissue free fatty acids. The rates of both lipolysis and esterification were greater in these tissues so that no net change in total free fatty acids took place. However, the lipolytic system in tissues treated with triiodothyronine showed greater than normal response to epinephrine. 

HORMONAL EFFECTS ON THE LIPOLYTIC ACTIVITY OF ADIPOSE TISSUE INCUBATED IN VITRO... 

In their excellent study on the comparative physiology of adipose tissue, Rudman and Di Girolamo have also noted remarkable differences between the rat and other species. The study includes an examination of the lipolytic effects of other hormones, in particular a number of pituitary peptides. Of great importance is the critical analysis made by the authors of the limitations of the experimental data. These limitations should be clearly kept in mind. 

Glucagon can be v ashed off adipose tissue without leaving any residual lipolytic activity. This indicates that the glucagon-triggered activation of lipolysis is quickly reversible when the hormone is removed. 

A. common point of action in adipose tissue for the lipolytic hormones is the adenyl-cyclase system (Sutherland et al. 196 ) an enzyme probably located on the cell membrane (Davoren and Sutherland, 1963) which catalyses the synthesis of adenosine 3 5 phosphate (cyclic 3 5 AMP). 

The response of the adipose tissue preparations to the lipolytic hormones is modulated by several physiological factors glucose metabolism, glycogen storage, presence of insulin and, probably, the presence of a newly observed factor, the prostaglandins (PG) which are the most powerful inhibitors of FFA mobilization in adipose tissue "in vitro" ( Steinberg et al. 1961) and "in vivo" (Carlson et al. 1963 Berti et al. 1964). 

Our results may be interpreted in different ways higher levels of cyclic 3 5 AMP may be produced in EFA-deficient rats or 3 5 AMP may be slowly metabolized or eventually normal concentrations of 3 5 AMP may activate more effectively the lipolytic system. This suggests however that the 3 5 AMP system which is activated in rat adipose tissue by catecholamines, ACTH and the peptide hormones, represents a point of attack for prostaglandins as well, and that the interaction between lipolytic hormones and this physiological inhibitor of lipolysis may be critical for the understanding of normal and pathologic levels of lipolysis. 

Metaraminol is almost devoid of lipolytic activity and it acts therefore as a powerful inhibitor of FFA mobilization The well-known observation that insulin can decrease the release of FFA and glycerol from adipose tissue in vitro, even in the absence of glucose and lipolytic hormones, has prompted investigators to see whether drugs known to lower blood glucose such as sulphonylureas have a similar activity. In isolated adipose tissue cells, sulphonylmeas (tolbutamide, tolazamide) decrease the rate of FFA release in a way similar to that of insulin. This effect is not mediated by insulin because it is still present when anti-insulin is added and it seems to be a direct effect, possibly at the level of adenyl cyclase activation. Accordingly, the intravenous injection of tolbutamide in man reduces plasma FFA levels. 

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