Adipose tissue fatty acid release

Only the free form of the fatty acid precursors of eicosanoids can be utilized by the enzymes for conversion to the biologically active metabolites. However, the amount of precursor free fatty acid in the cytoplasm and circulating is usually low and so too is basal eicosanoid formation. Eurthermore, basal eicosanoid formation may depend on dietary and adipose tissue fatty acid composition. The amount of eicosanoid precursor free fatty acids is controlled to a large extent by incorporation and release from cellular phospholipids. Which eicosanoids are produced during stimulated synthesis may depend on membrane fatty acid composition as well as the cell type involved. Dietary fatty acid composition, therefore, has the potential to effect basal and stimulated synthesis of eicosanoids and influence endothelial function and thrombotic and inflammatory responses. 

Niacin (vitamin B3) has broad applications in the treatment of lipid disorders when used at higher doses than those used as a nutritional supplement. Niacin inhibits fatty acid release from adipose tissue and inhibits fatty acid and triglyceride production in liver cells. This results in an increased intracellular degradation of apolipoprotein B, and in turn, a reduction in the number of VLDL particles secreted (Fig. 9-4). The lower VLDL levels and the lower triglyceride content in these particles leads to an overall reduction in LDL cholesterol as well as a decrease in the number of small, dense LDL particles. Niacin also reduces the uptake of HDL-apolipoprotein A1 particles and increases uptake of cholesterol esters by the liver, thus improving the efficiency of reverse cholesterol transport between HDL particles and vascular tissue (Fig. 9-4). Niacin is indicated for patients with elevated triglycerides, low HDL cholesterol, and elevated LDL cholesterol.3... 

Answer C. Insulin increases glucose transport in only two tissues, adipose and muscle. The major site of glucose uptake is muscle, which decreases hyperglycemia. Glucose and ketone transport and metabolism are insulin independent in the brain (choice D). Insulin would slow gluconeogenesis (choice A) and fatty acid release from adipose (choice B). Insulin would inhibit glycogenolysis in the liver (choice E). 

Figure 7.6 Release of fatty acids from the triacylglycerol in adipose tissue and their utilisation by other tissues. Fatty acids are long-chain fatty acids, abbreviated to FFA (see below). Hydrolysis (lipolysis) of triacylglycerol in adipose tissue produces the long-chain fatty acids that are released from the adipocytes into the blood for oxidation by various tissues by P-oxidation (see below).

In adipose tissue, the increased concentration of cyclic AMP activates the hormone-sensitive lipase to increase the rate of Upolysis and hence fatty acid release from adipose tissue. This increases the plasma level of fatty acids and hence their oxidation by muscle (see Chapter 7). 

The function of glucagon is to respond rapidly to an acute fall in the blood glucose level by stimulating glucose release by the liver and fatty acid release by adipose tissue. 

Figure 21.21 Diagram to illustrate the intertissue triacylglycerol/ fatty acid cycle, (i) Fatty acids released from adipose tissue are esterified in the liver, (ii) The triacylglyceral is released in the form of VLDL. (iii) The triacylglycerol in the latter is hydrolysed in the capillaries in the adipose tissue. Some fatty acids are taken up by adipose b ssue, but about 30% are release in the circulation that give life to the extracellular cycle. The intracellular cycle exists in the adipocytes.

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. 

FIGURE 17-1 Processing of dietary lipids in vertebrates Digestion and absorption of dietary lipids occur in the small intestine, and the fatty acids released from triacylglycerols are packaged and delivered to muscle and adipose tissues. The eight steps are discussed in the text. 

Insulin also stimulates the storage of excess fuel as fat (Fig. 23-26). In the liver, insulin activates both the oxidation of glucose 6-phosphate to pyruvate via glycolysis and the oxidation of pyruvate to acetyl-CoA. If not oxidized further for energy production, this acetyl-CoA is used for fatty acid synthesis in the liver, and the fatty acids are exported as the TAGs of plasma lipoproteins (VLDLs) to the adipose tissue. Insulin stimulates TAG synthesis in adipocytes, from fatty acids released... 

Fatty acids released by lipoprotein lipase are taken up by the tissue where this enzyme is located, where they may be oxidized (see later) or stored in the form of triglycerides, such as adipose tissue. Triglyceride biosynthetic enzymes are located in the endoplasmic reticulum. Triglyceride biosynthesis is summarized in Figure 19.4. It is seen that dihydroxyacetone phosphate (see Chapter 18) is a key intermediate. It can combine with an acyl residue carried by acyl coenzyme A... 

In the -in vivo situation, the ketogenic action of glucagon is most prominent in states of insulin deficiency. This can be explained because insulin normally suppresses the effect of glucagon on hepatic cAMP levels [170] and inhibits the action of the hormone on lipolysis, i.e., fatty acid release in adipose tissue [171]. 

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). 

The synthesis of triacylglycerol takes place in the endoplasmic reticulum (ER). In liver and adipose tissue, fatty adds in the cytosol obtained from the diet or from de novo synthesis of palmitic add become inserted into the ER membrane. The reactions are shown in Fig. 13-10. Membrane-bound acyl-CoA synthetase activates two fatty acids, and membrane-bound acyl-CoA transferase esterifies them with glycerol 3-phosphate, to form phosphatidic acid. Phosphatidic acid phosphatase releases phosphate, and in the membrane, 1,2-diacylglycerol is esterified with a third molecule of fatty acid. 

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. 

FIGURE 4 8 Oxidation of carbohydrate and fatty adds for the production of energy. In the resting state, glycogen in the liver is broken down to glucose units however, both liver (kft) and muscle (right) derive most of their energy from fatty acids released from adipose tissue into the bloodstrecim and oxidized via the Krebs cycle. When carbohydrate is oxidized in the liver, it tends to be released into the bloodstream as pyruvate and lactate. 

In muscle and adipose tissue, insulin promotes transport of glucose and other monosaccharides across cell membranes it al.so facilitates tran.sport of amino icids, potassium ion.s. nucleosides, and ionic phosphate. Insulin also activates certain enzymes—kinases and glycogen. synthetase in muscle und adipose tissue. In adipose tissue, insulin decreases the release of fatty acids induced by epinephrine or glucagon. cAMP promotes fatty acid release from adipose ti.ssue therefore. it is pos.sible that insulin decreases fatty acid release by reducing tissue levels of cAMP. Insulin also facilitates the incorporation of intracellular amino acids into protein. 

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