Signalling mechanisms regulating lipolysis

Adipose tissue plays an important role providing energy to other tissues and functioning as an energy reserve organ. The energy supply is produced by triglycerides stored in a large vacuole representing approximately 95% of adipocyte volume. In the fasting period, triglyceride hydrolysis produces glycerol and free fatty acids which are important oxidative fuels for other tissues such as liver, skeletal muscle, kidney and myocardium. Hormone-sensitive lipase (HSL) is the enzyme that hydrolyzes intracellular triacylglycerol and diacylglycerol, and is one of the key molecules controlling lipolysis. Hormones and physiological factors such as dieting, physical exercise and ageing regulate intensively the release of glycerol and free fatty acids from adipocytes. One of the best known mechanisms that activate lipolysis in the adipocyte is the cAMP dependent pathway. cAMP production is modulated by hormone receptors coupled to Gs/Gi family of GTP binding proteins, such as beta-adrenergic receptors, whereas cAMP degradation is controlled by modulation of phosphodiesterase activity, increased by insulin receptor signalling. cAMP activates PKA which activates HSL by promoting its phosphorylation. Hormonal control of lipolysis can also be achieved by receptors coupled G proteins of the Gq family, through molecular mechanisms that involve PKC and MAPK, which are currently under investigation. cGMP and PKG have also been found to activate lipolysis in adipocytes. In this review we have compiled data from literature reporting both the classical and the alternative mechanisms of lipolysis.     

Antidiuretic hormone and lipolysis.

Lysine vasopressin did not increase plasma FFAs level in man and in rat Pitressin and lysine vasopressin did not influence adenyl cyclase activity in rat epididymal fat pad, while ornithine vasopressin induced a statistically significant adenyl cyclase increment. These findings suggest that the adipokinetic acticity of ADH which has been correlated only with the amino acid arginine is also correlated with ornithine.     

Substrate-dependent lipolysis induced by isoproterenol

The relationship between isoproterenol-induced lipolysis and the phosphorylation of perilipin and hormone-sensitive lipase (HSL) was examined using cell-free systems consisting of lipid droplets isolated from rat fat cells and HSL, and/or trioleoylglycerol emulsified with gum arabic and HSL. Isoproterenol was found to stimulate lipolysis in the cell-free system with the lipid droplets without an increase in the phosphorylation of either perilipin or HSL. On the other hand, no stimulation of lipolysis was found in the cell-free system containing lipid droplets despite increases in the phosphorylation of perilipin and HSL. In the cell-free system consisting of trioleoylglycerol emulsified with gum arabic and HSL, neither isoproterenol nor increases in the phosphorylation of perilipin and HSL accelerated lipolysis. These results suggest that isoproterenol-induced lipolysis may not be mediated through the phosphorylation of perilipin and HSL, and may rather be dependent on the substrate of HSL.     

Hormone-stimulated lipolysis in cardiac myocytes.

Type L hormone-sensitive lipase (HSL) activity was increased approx. 35% above control in cardiac myocytes incubated for 15 min with 5 nM-adrenaline. Concomitantly. adrenaline-stimulated myocytes had a lower triacylglycerol content, released more non-esterified fatty acid and had a higher intracellular concentration of cyclic AMP than did myocytes incubated without hormone. The lipase activity measured in adrenaline-stimulated and non-stimulated myocytes was stable in acetone/diethyl ether, stimulated by serum and inhibited by NaCl. These properties are consistent with the type L designation of this HSL. The finding that type L HSL is stimulated by adrenaline indicates that the enzyme that is being activated is found in the cell and not associated with an extracellular compartment of the myocardium.     

Microbial lipolysis at low temperatures.

It was found that lipase production during the growth of Pseudomonas fluorescens was not a function of the total number of bacteria. The optimal temperatures for bacterial growth and lipase production were determined as 20 and 8 degrees C, respectively. The lipolytic activity was studied in emulsions of olive oil at temperatures ranging from +8 to -30 degrees C. After an initially rapid lipolysis, the reactions retarded at different levels depending on storage temperature. Transference to a higher temperature resulted in a resumed lipolysis. Also, at low temperatures, lipolysis was studied as a function of water activity and was found to occur in dehydrated substrates.     

Effect of oestradiol on catecholamine-stimulated lipolysis

The authors studied the effect of a single in vivo dose of oestradiol (OE) on adrenergic lipolysis in the epididymal adipose tissue of adult and juvenile male rats, and the effect of OE on plasma free fatty acids (FFA), cholesterol and beta-lipoprotein levels at various intervals after its administration. It was found that OE injected 24 h beforehand in vivo (s.c.), in doses of 100 and 200 micrograms X kg-1 body weight, significantly potentiated the lipid-mobilizing action of the catecholamines noradrenaline (NOR) and isoprenaline (ISO) in adult rats (the action of ISO was potentiated more intensively); in addition, the adipose tissue became more sensitive to the action of NOR, but not of ISO. Raising the dose of OE to 400 micrograms X kg-1 did not enhance the potentiation of the lipolytic action of the catecholamines any further; on the contrary, the lipid mobilizing effect of the catecholamines was potentiated less than after half this dose. Following the s.c. injection of an oily OE solution, the lipolytic effect was potentiated after more than 7 h; the potentiation was strongest after 12 h, but only as far as the maximum attainable degree of lipolysis was concerned. Potentiation of adrenergic lipolysis was found only in adult male rats. In male rats weighing 130-150 g the lipolytic effect of catecholamines (in mumol/g adipose tissue) was significantly greater than in adult animals and the pre-administration of OE did not potentiate adrenergic lipolysis any further. Determination of plasma FFA, cholesterol and beta-lipoprotein levels 1, 2, 4 and 6 hours after the s.c. injection of OE showed only nonsignificant changes (an increase in FFA and a decrease in cholesterol). The authors consider it important to distinguish between the effect of OE on catecholamine-stimulated lipolysis in depot adipose tissue and its effect on lipid metabolism. In their opinion, the dose-dependent effect of OE on muscular and metabolic adrenergic reactions could be one of the factors co-reversible for certain side reactions to steroid contraceptives.     

脂肪组织甘油三酯水解酶参与脂肪分解调控

循环中游离脂肪酸增高与肥胖、胰岛素抵抗和2型糖尿病密切相关,其主要来源于脂肪细胞内甘油三酯水解.调控脂肪分解的脂肪酶主要包括激素敏感脂肪酶(hormone-sensitive lipase,HSL)和最近发现的脂肪组织甘油三酯水解酶(adipose triglyceride lipase,ATGL),后者主要分布在脂肪组织,特异水解甘油三酯为甘油二酯,其转录水平受多种因素调控.CGI-58(属于α/β水解酶家族蛋白),可以活化ATGL,基础条件下该蛋白和脂滴包被蛋白(perilipin)紧密结合于脂滴表面,蛋白激酶A激活刺激脂肪分解时,CGI-58与perilipin分离,进而活化ATGL.     

Peptide hormones and lipolysis in rabbit adipocytes

Fifty peptides and hormones from the hypophysis, hypothalamus, gastrointestinal tract and from other origins were tested for lipolytic activity in the isolated rabbit fat cell. Eight peptides derived from the precursor hormone proopiocortin stimulated glycerol release while all the other peptides and hormones showed no lipolytic activity. The most potent lipolytic peptide was alpha-MSH which also had the lowest minimal effective dose, followed by beta-lipotropin, ACTH and beta-MSH. The lipolytic activity was not influenced by the use of different collagenases or the cells from different breeds of rabbits.     

Interfacial mechanism of lipolysis as self-regulated process

Obesity is a serious public health concern with an increasing prevalence worldwide. The diet contributes strongly to this problem and high-fat food leads to unhealthy conditions. Fat digestion is an energy intensive process as it requires hydrolysis to allow the body to profit from this nutrient. This additional energy expenditure is also present in a highly redundant hormonal regulation system for fat storage which is converted in not a readily accessible form (therefore, an upstream is required in order to tackle fat-related diseases).