Lipolysis regulation

As to be expected from a peptide that has been highly conserved during evolution, NPY has many effects, e.g. in the central and peripheral nervous system, in the cardiovascular, metabolic and reproductive system. Central effects include a potent stimulation of food intake and appetite control [2], anxiolytic effects, anti-seizure activity and various forms of neuroendocrine modulation. In the central and peripheral nervous system NPY receptors (mostly Y2 subtype) mediate prejunctional inhibition of neurotransmitter release. In the periphery NPY is a potent direct vasoconstrictor, and it potentiates vasoconstriction by other agents (mostly via Yi receptors) despite reductions of renal blood flow, NPY enhances diuresis and natriuresis. NPY can inhibit pancreatic insulin release and inhibit lipolysis in adipocytes. It also can regulate gut motility and gastrointestinal and renal epithelial secretion. 

The Provision of Glycerol 3-Phosphate Regulates Esterification Lipolysis Is Controlled by Hormone-Sensitive Lipase (Figure 25-7)... 

Holm C et al Molecular mechanisms regulating hormone sensitive lipase and lipolysis. Annu Rev Nutr 2000 20 365. 

The neurohormonal control of lipid metabolism chiefly affects the mobilization and synthesis of triglycerides in the fat tissue. The lipolysis in tissues is dependent upon the activity of triglyceride lipase. All the regulators that favour the conversion of the inactive (nonphosphorylated) lipase to the active (phosphoiylated) one, stimulate the lipolysis and the release of fatty acids into the blood. Adrenalin... 

The regulation of fat metabolism is relatively simple. During fasting, the rising glucagon levels inactivate fatty acid synthesis at the level of acetyl-CoA carboxylase and induce the lipolysis of triglycerides in the adipose tissue by stimulation of a hormone-sensitive lipase. This hormone-sensitive lipase is activated by glucagon and epinephrine (via a cAMP mechanism). This releases fatty acids into the blood. These are transported to the various tissues, where they are used. 

Figure 16.1 The glucose/fatty add cycle. The dotted Lines represent regulation. Glucose in adipose tissue produces glycerol 3-phosphate which enhances esterification of fatty acids, so that less are available for release. The effect is, therefore, tantamount to inhibition of lipolysis. Fatty acid oxidation inhibits pyruvate dehydrogenase, phosphofructokinase and glucose transport in muscle (Chapters 6 and 7) (Randle et al. 1963).

Major effector proteins for G-pro-tein-coupled receptors include adenylate cyclase (ATP intracellular messenger cAMP), phospholipase C (phos-phatidylinositol intracellular messengers inositol trisphosphate and di-acylglycerol), as well as ion channel proteins. Numerous cell functions are regulated by cellular cAMP concentration, because cAMP enhances activity of protein kinase A, which catalyzes the transfer of phosphate groups onto functional proteins. Elevation of cAMP levels inter alia leads to relaxation of smooth muscle tonus and enhanced contractility of cardiac muscle, as well as increased glycogenolysis and lipolysis (p. 

The degradation of fats (lipolysis) is catalyzed in adipocytes by hormone-sensitive lipase [2]—an enzyme that is regulated by various hormones by cAMP-dependent interconversion (see p. 120). The amount of fatty acids released depends on the activity of this lipase in this way, the enzyme regulates the plasma levels of fatty acids. 

Growth hormone, or somatotropin, is a protein that stimulates linear body growth in children and regulates cellular metabolism in both adults and children. Growth hormone stimulates lipolysis, enhances production of free fatty acids, elevates blood glucose, and promotes... 

Potassium [7440-09-7], K, is the third element in the alkali metal series. The name designation for the element is derived from potash, a potassium mineral the symbol from the German name kalium, which comes from the Arabic qili, a plant. The ashes of these plants (a/ qih) were the historical source of potash for preparing fertilizers (qv) or gun powder. Potassium ions, essential to plants and animals, play a key role in carbohydrate metabolism in plants. In animals, potassium ions promote glycolysis, lipolysis, tissue respiration, and the synthesis of proteins (qv) and acetylcholine. Potassium ions are also believed to function in regulating blood pressure. 

Sautin, Yu. Yu. (1989). The problem of regulation of the adaptive changes of lipoge-nesis, lipolysis and lipid transport in fish (In Russian). Uspekhi Sovremennoy Biologii 107,131-149. 

Fig. 21.2 Major effects of AMPK activation on numerous tissues. AMPK plays a key role in regulating whole body energy storage and expenditure. In hypothalamus, AMPK is involved in regulation of satiety and food intake. Activation of AMPK in the hypothalamus increases food intake, whereas inhibition decreases intake. In peripheral tissues such as skeletal muscle and liver, activation of AMPK increases energy expenditure by stimulating mitochondrial genesis and energy substrate utilization. AMPK also regulates lipolysis in adipose tissue and insulin secretion in pancreas.

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],... 

Arimoto, I., Matsumoto, C., Tanaka, M., Okuhira, K., Saito, H., and Handa, T. (1998), Surface composition regulates clearance from plasma and triolein lipolysis of lipid emulsions, Lipids, 33,773-779. 

A third factor regulating the speed of lipolysis is the hydrophobicity of the ester. The normal substrates of lipase—the natural triglycerides— are insoluble in water, and the enzyme acts at the oil-water interface. Thus, lipases have been defined as esterases that act on insoluble substrates at such interfaces. However, triglycerides that are similar in steric and inductive effects may still react with different velocities even if all reactions take place at oil-water interfaces. For instance, emulsified tributyrin is hydrolyzed 20 times faster than emulsified triacetin. This difference is caused by the different hydrophobicity of the triglycerides not by the different chain lengths of butyric and acetic acid. 

Other metabolic effects. In addition to enabling glucose to pass across cell membranes, the transit of amino acids and potassium into the cell is enhanced. Insulin regulates carbohydrate utilisation and energy production. It enhances protein synthesis. It inhibits breakdown of fats (lipolysis). An insulin-deficient diabehc (Type 1) becomes dehydrated due to osmotic diuresis, and is ketotic because fats break down faster than the ketoacid metabolites can be metabolised. 

Fig. 10.10 Regulatory Interations of Fatty Acid Synthesis and Oxidation in Liver Note that a lack of insulin results in a release of fatty acids from adipose. Regulation of Hormone-Sensitive Lipase (Lipolysis) "Fasted" State (Fig. 10.11)...

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