Lipolytic effect

Stimulation of protein synthesis in many tissues Mobilization of depot lipids from adipose tissue (lipolytic effect)... 

Effects on lipid metabolism Glucagon favors hepatic oxidation of fatty acids and the subsequent formation of ketone bodies fan acetyl CoA. The lipolytic effect of glucagon in adipose tissue is minimal in humans. 

Clegg (1980) reported that bovine serum and high-density lipoprotein (HDL) caused an increase in free fatty acid levels in unpasteurized bulk milk. Lipoprotein free serum, apo HDL, all individual HDL tested, and the unfractionated C-peptide fractions had no lipolytic effect. HDL-lipid in the presence of 2 C-peptides and the combination of HDL-lipid with unfractionated C-peptide caused a considerable stimulation of lipolysis. 

There have been frequent difficulties relating physiological effects to cyclic AMP levels. For example, adenosine inhibits the effect of noradrenaline on cyclic AMP accumulation in rat fat cells but does not interfere with the lipolytic effect of the catecholamine [58]. Both ACTH and its o-nitrophenyl sulphenyl derivative stimulate corticosterone synthesis in isolated rat adrenal cells to the same maximal rate, but the analogue has a 30- to 100-fold smaller effect than ACTH on cyclic AMP accumulation [60]. 

Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K, Offermanns S (2003) PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med 9 352-355... 

G. Fruhbeck, M. Aguardo, and J.A. Martinez, In vitro lipolytic effect of leptin on mouse adipocytes evidence for a possible autocrine/paracrine role of leptin, Biochem. Biophys. Res. Commun., 1997, 240, 590-594. 

Effects on llpolysis - In a recent article. Butcher reviews the history of their experiments on the role of the cyclic AMP in the lipolytic process. Their investigations showed an increase in the concentration of cyclic AMP upon the addition of epinephrine to fat pads vitro, followed by a stimulation of the release of free fatty acids. Caffeine, a known inhibitor of the phosphodiesterase which degrades cyclic AMP, acted synergistically with epinephrine on the accumulation of cyclic AMP and the subsequent release of free fatty acids it should be noted that the lipolytic effect of epine-... 

Stimnlation of the H2 receptors elicits a variety of responses, the most widely stndied of which is gastric acid secretion from the parietal cells of the gastric glands. However, many other effects mediated by H2 receptors are manifested in peripheral tissnes. These inclnde the positive chronotropic action in the anricnlar mnscle, the inotropic action in the ventricnlar mnscle, and the lipolytic effect in fat cells. In addition, the extensive nse of cimetidine has led to the synthesis and marketing of more specific and efficacious analogs with pharmacologic properties (see Table 10). 

The lipolytic effects of GH increase free fatty acid levels in the blood bathing muscle. These fatty acids are preferentially used as fuel, indirectly suppressing glucose uptake by muscle cells. Through the effects on glucose uptake, the rate of glycolysis is proportionately reduced. 

In conclusion, the major effect of growth hormone (lipolytic) on lipid metabolism is opposite to that of insulin (stimulates fatty acid deposition). Small doses of growth hormone may elicit an insulinlike effect that is transient, often prolonged by incubation, and replaced by a lipolytic effect. 

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. 

The oxidation rate of fatty acids appears to be proportional to the concentration in plasma, and, as mentioned above, major products are ketone bodies, which can serve as respiratory fuel. In moderate forms of ketosis, glucagon secretion is antagonized by that of insulin consequently ketone bodies do not accumulate because g their utilization by peripheral tissues is accelerated and their genesis interrupted. In several forms of ketosis, homeostasis breaks down. In diabetics, the lipolytic effect of glucagon is not compensated for, and the increase in free fatty acids and ketone bodies in plasma is unchecked. Moreover, utilization of ketone bodies by peripheral tissue could be reduced. 

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). 

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 ... 

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. 

Gonzalez-Santos, P. and Grande, F. (1975). Age influence on the lipolytic effect of glucagon in geese. Proc. Soc. Exptl. Biol. Med. 

In these experiments there was a poor correlation between the effects of insulin on cyclic AMP levels and lipolysis. When insulin had its most pronounced anti-lipolytic effects (i. e., in the presence of epinephrine alone) it did not appear to lower cyclic AMP, and when insulin lowered cyclic AMP (in tissue incubated with epinephrine and caffeine) it did not inhibit lipolysis. A small rise in the cyclic AMP level in adipose tissue (from about 1. 5 x 10 7 mmoles/g to 3. 5 x 10"7 mmoles/ g) is enough to stimulate lipolysis maximally and cyclic AMP... 

The opposite effect on the adenyl cyclase apparently is produced by insulin, which therefore restrains the lipolytic effect of epinephrine, norepenephrine,... 

Fig. 1. Comparison of the inhibition of the lipolytic effect of norepinephrine by PGE in vitro.

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