Adipose tissue free fatty acid release

Excess adiposity, particularly the abdominal obesity associated with increased waist circumference, is associated with insulin resistance, hypertension, and proinflammatory states. The prevalence of this complex of comorbidities associated with obesity, now referred to as the metabolic syndrome, is reaching epidemic proportions in the United States (Grundy et al., 2004 Roth et al., 2002). Indeed, increased abdominal adiposity is one of a cluster of factors that are used in the diagnosis of metabolic syndrome. Abdominal tissue in the trunk occurs in several compartments, including subcutaneous and intraperitoneal or visceral fat. Visceral fat in particular appears to contribute to perturbed fuel metabolism by at least two mechanisms. First, hormones and free fatty acids released from visceral fat are released into the portal circulation and impact directly on metabolism of the liver. Second, the visceral adipose depot produces a different spectrum of adipocytokines than that produced by subcutaneous fat (Kershaw and Flier, 2004). 

Nicotinic acid. This reduces the plasma levels of both VLDLs and LDLs by inhibiting hepatic VLDL secretion, as well as suppressing the flux of free-fatty-acid release from adipose tissue by inhibiting lipolysis. Because of its ability to cause large reductions in circulating levels of cholesterol, nicotinic acid is used to treat Type 11, HI, IV and V hyperlipopro-teinaemias. 

The activity of the lipase has also been assayed with the ultramicro method of Novak [171] to determine net free fatty acid release from endogenous substrate [172]. Incubation of rat adipose tissue homogenate was carried out in 40 mM phosphate buffer, pH 6.8, in the presence of 30 mM EDTA and 2% bovine serum albumin. 

Various situations yield to induction of fatty acid catabolism in the liver such as birth which corresponds to a transition in energy source from a carbohydrate-rich to a lipid-rich regimen fasting, which is associated with free fatty acid release in the blood due to lipolysis of the adipose tissue as well as exposure to various xenobiotics. Several biochemical mechanisms exist to rapidly control the activity of the different enzymes involved in fatty acid oxidation. However, the transcriptional regulation of the expression of these enzymes is an additional level of control necessary for long-term maintenance of the organism energy balance. 

Rashef and Shapiro (1960) reported that pretreatment of adrenalecto-mizc d rats with either epinephrine or eortisone inereased the depressed rate of free fatty acid release by their mesenteric adipose tissue in vitro however, maximal effects were, obtained only when both were given. It was further pointed out that epinephrine alone was highly effective in restorii the depressed rate of free fatty acid release by tissue from adrenal demedul-lated rats. Reshef and Shapiro (1960) also observed that pretreatment of starved intact rats with cortisone had little effect on the release of free fatty acid by mesenteric adipose tissue. Such treatment, however, inereased and prolonged the response of tissue removed from rats injected with epinephrine (sec Section VI, A). These results may reflect in part the effects of glucocorticoid administration on the adipose tissue stores of the intact animal, but the interesting relation between the effects of epinephrine and adrenocortical steroids on the release of free fatty acids deserves further study. 

Debons and Schwartz (1959, 1961) have observed that the release in vitro of free fatty acid by adipose tissue from rats rendered hypothyroid by propylthiouracil is less than that from normal animals, whereas the release of free fatty acid by epididymal adipose tissue from animals rendered hyperthyroid by the administration of triiodothyronine or thyroxine is greater than that from euthyroid rats (Debons and Schwartz, 1959, 1961 Hagen, 1960). The addition of triiodothyronine to the incubation medium had no effect on the rate of free fatty acid release by adipose tissue from euthyroid rats (Debons and Schwartz, 1959, 1961). The release of free fatty acids by adipose tissue from hyperthyroid rats is markedly reduced by the addition of insulin (Hagen, 1960). 

Among 24 compounds containing the tetrazole function prepared by Holland and Pereira [70], 5-(3-pyridyl)-tetrazole (XIII) was found to depress plasma-free fatty acid levels in the fasted dog most effectively. The hypoHpidemic activity of XIII was comparable to that of nicptinic and 3-pyridyl-acetic acids. In fact, the duration of activity was approximately 5 hours which is three times longer than that of nicotinic acid. Moreover, no rebound effect was observed after the hypoHpidemic activity of XIII, while the short inhibitory action of nicotinic acid was followed by a rise of plasma-free fatty acid concentration above the control level in the fasted dog. In contrast, compound XIII was found to be about 3,000 times less potent than nicotinic acid in the in vitro test in which the inhibition of norepinephrine-induced free fatty acid release from isolated adipose tissue was measured. In this assay, 3-pyridyl-acetic acid (IV) was approximately 600 times less active than nicotinic acid. PicoHnic acid and isonicotinic acid were even less active. The metaboHtes of nicotinic acid in man, namely, nicotinic acid amide, iV -methylnicotinamide and nicotinuric acid, were found to be about 10,000 times less active as Hpolysis inhibitors than nicotinic acid. Based on these findings, 5-(3-pyridyl)-tetrazole... 

Long chain fatty acids derived from the adipose tissue are released through the action of the adipose tissue lipase (Vaughan et al., 1964) and the free fatty acids released from the adipose tissue are transported in the circulation bound to albumin. As it well known, lipase activity increases in response to p-adrenergic stimulation via the activation of adenyl cyclase and the second messenger, cyclic AMP (Butcher, 1972). On the other hand,... 

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. 

Increases in plasma non-esterilled fatty acids are encountered in diabetic ketoacidosis. In this condition there is insufficient a-glycerophosphate (derived from glycolysis) for the free fatty acids (released from adipose tissue) to combine with to re-form triglycerides. As a result of this, the free fatty acids are converted to ketone bodies. 

Triacylglycerols must be hydrolyzed by a lipase to their constiment fatty acids and glycerol before further catab-ohsm can proceed. Much of this hydrolysis (hpolysis) occurs in adipose tissue with release of free fatty acids into the plasma, where they are found combined with semm albumin. This is followed by free fatty acid uptake into tissues (including hver, heart, kidney, muscle, lung, testis, and adipose tissue, but not readily by brain), where they are oxidized or reesterified. The uti-hzation of glycerol depends upon whether such tissues... 

A principal action of insufin in adipose tissue is to inhibit the activity of hormone-sensitive lipase, reducing the release not only of free fatty acids but of glycerol as well. Adipose tissue is much more sensitive to insulin than are many other tissues, which points to adipose tissue as a major site of insufin action in vivo. 

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. 

Triacylglycerol is the main storage Hpid in adipose tissue. Upon mobihzation, free fatty acids and glycerol are released. Free fatty acids are an important fuel source. 

In adipose tissue, the effect of the decrease in insulin and increase in glucagon results in inhibition of lipo-genesis, inactivation of lipoprotein lipase, and activation of hormone-sensitive lipase (Chapter 25). This leads to release of increased amounts of glycerol (a substrate for gluconeogenesis in the liver) and free fatty acids, which are used by skeletal muscle and liver as their preferred metabolic fuels, so sparing glucose. 

Adipose tissue releases free fatty acids in statvation, and these ate used by many tissues as fuel. Futthet-mote, in the hvet they ate the substtate fot synthesis of ketone bodies. 

Intravenous lipid emulsion particles are hydrolyzed in the bloodstream by the enzyme lipoprotein lipase to release free fatty acids and glycerol. Free fatty acids then are be taken up into adipose tissue for storage (triglycerides), oxidized to energy in various tissues (e.g., skeletal muscle), or recycled in the liver to make lipoproteins. 

Because digestion of food in the intestinal tract is dispensable and only counterproductive, the propulsion of intestinal contents is slowed to the extent that peristalsis diminishes and sphinc-teric tonus increases. However, in order to increase nutrient supply to heart and musculature, glucose from the liver and free fatty acid from adipose tissue must be released into the blood. The bronchi are dilated, enabling tidal volume and alveolar oxygen uptake to be increased. 

The release of free fatty acids from adipose tissue (lipolysis) is mediated through (33-adrenoceptors. Isoproterenol is the most potent agonist, followed by epinephrine and norepinephrine. 

Triacylglycerol. Triglyceride a compound consisting of three molecules of fatty acids esterified to glycerol. It is a neutral fat synthesized from carbohydrates for storage in animal adipose cells. On enzymatic hydrolysis, it releases free fatty acids in the blood. Tuberculosis. Any of the infectious diseases of man and animals caused by species Mycobacterium and characterized by the formation of tubercles and caseous necrosis in the tissues. 

Chylomicrons deliver tiiacylglycerols to tissues, where lipoprotein lipase releases free fatty acids for entry into cells. Triacylglycerols stored in adipose tissue are mobilized by a hormone-sensitive triacylglycerol lipase. The released fatty acids bind to serum albumin and are carried in the blood to the heart, skeletal muscle, and other tissues that use fatty acids for fuel. 

Fig. 21-20 see also Fig. 17-1). Flux through this tri-acylglycerol cycle between adipose tissue and liver may be quite low when other fuels are available and the release of fatty acids from adipose tissue is limited, but as noted above, the proportion of released fatty acids that are reesterified remains roughly constant at 75% under all metabolic conditions. The level of free fatty acids in the blood thus reflects both the rate of release of fatty acids and the balance between the synthesis and breakdown of triacylglycerols in adipose tissue and liver. 

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