Activity of Adipose Tissue

Metabolic Activity of Adipose Tissue A. Glucose Metabolism 

The presence of the glycolytic pathway in adipose tissue is supported by studies of the metabolism of glucose-C. Weber et al. (1960) were unable to detect significant fructose-l,6-diphosphatasc activity, a result suggesting that glycolysis is probably irreversible. These same workers, as well as MacLeod el al. (1960) found essentially no glucose-O-phosphatase activity an inactivity which supports the view that adipose tissue does not release free glucose. The relative recoveries of C in the CO2 produced by adipose 

Uridine triphosphate 4- glucose-l-phosphate UDPG + pyrophosphate (1) UDPG -f glycogen primer — glycogen 4- uridine diphosphate (2) 

Recent studies of the composition of human adipose tissue indicate that 99% of the lipid is in the form of triglycerides, cholesterol representing 0.3% and phospholipids 0.1 % (Hirsch etal., 1960). Hirsch (1962) has shown that the fatty acid composition of human subcutaneous adipose tissue taken from various sites is similar to that observed in samples of adipose tissue taken from the psoas, omental, and perinephric areas. Large amounts of palmitic and oleic acid are present, but less linoleic, stearic, and palmitoleic acid. Six fatty acids account for more than 90% of the total these are myristic, palmitic, oleic, stearic, linoleic, and palmitoleic acids (Hirsch, 1962). In man, the linoleic acid is probably derived from dietary fat (Hirsch, 1962). If rat epididymal adipose tissue is incubated with acetate- 

Long-Chain Fatty Acid Synthesis from Carbohydrate 

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Niacin reduces plasma LDL cholesterol, lipoprotein (a), triglycerides and raises HDL cholesterol in all types of hyperlipoproteinemia [26]. Although available on the market for more than 40 years, the mechanisms of action of niacin are poorly understood. Putative mechanisms are the activation of adipose tissue LPL, diminished HTGL activity, a reduced hepatic production and release of VLDL, and composi-... 

Female bw at mating high (increased adiposity) Mettin -. reduced Fertility, reduced Both effects likely related to hormonal activity of adipose tissue... 

Decreased uptake of fatty acids In fasting, lipoprotein lipase activity of adipose tissue is low. Consequently, circulating triacyl-glycerol of lipoproteins is not available for triacylglycerol synthesis in adipose tissue. 

Differences in the activity of lipoprotein lipase (LPL) between men and women may explain, in part, the different plasma lipid response to exercise (48). The activity of adipose tissue LPL is higher in women than in men, and higher in sedentary women than in male long distance runners (51). Since the Intra-vascular production of HDL is augmented by the catabolism of triglyceride rich lipoproteins by LPL (52), this hypothesis deserves further attention. 

Orr JS, Puglisi MJ, Ellacott KL, Lumeng CN, Wasserman DH, Hasty AH. Toll-like receptor 4 deficiency promotes the alternative activation of adipose tissue macrophages. Diabetes. 2012 61(11) 2718—2727. 

HORMONAL EFFECTS ON THE LIPOLYTIC ACTIVITY OF ADIPOSE TISSUE INCUBATED IN VITRO... 

In Type I diabetes mellitus, there is a severe deficiency (or total absence) of insulin due to an autoimmune attack on the cells that produce insulin, pancreatic j8-cells. The absence of insulin produces a deficiency in adipose tissue lipoprotein lipase. This causes sluggish catabolism of VLDL and leads to hypertriglyceridemia. Another mechanism by which insulin deficiency promotes increased VLDL levels is the failure to inhibit the activity of adipose tissue hormone-sensitive lipase. This enzyme hydrolyzes cytoplasmic triglyceride droplets. The fatty acids then go to the liver, where they are re-esterified to form triglycerides. These triglycerides are exported on VLDL particles. Since adipose tissue-derived fatty acids are an important substrate for hepatic VLDL triglycerides, the failure to suppress adipose tissue lipolysis is an important contributor to the enhanced rate of VLDL triglyceride secretion. 

Taylor, S. I., Mukherjee, C., and Jungas, R. L., 1973, Studies on the mechanism of activation of adipose tissue pyruvate dehydrogenase by insulin, /. Biol. Chem. 248 73. 

Notes Assuming a moderately active 70 kg man with 40% of body weight as muscle (28 kg), a liver weight of 1.8 kg, a plasma volume of 3 L, and 9 kg of adipose tissue. Endurance trained individuals store -125-150 mmol/kg wet muscle of glycogen in muscle and 400-700 mmol/kg wet tissue of glycogen in liver,... 

Figure 25-7. Metabolism of adipose tissue. Hormone-sensitive lipase is activated by ACTH, TSH, glucagon, epinephrine, norepinephrine, and vasopressin and inhibited by insulin, prostaglandin E, and nicotinic acid. Details of the formation of glycerol 3-phosphate from intermediates of glycolysis are shown in Figure 24-2. (PPP, pentose phosphate pathway TG, triacylglycerol FFA, free fatty acids VLDL, very low density lipoprotein.)...

Figure 25-8. Control of adipose tissue lipolysis. (TSH, thyroid-stimulating hormone FFA, free fatty acids.) Note the cascade sequence of reactions affording amplification at each step. The lipolytic stimulus is "switched off" by removal of the stimulating hormone the action of lipase phosphatase the inhibition of the lipase and adenylyl cyclase by high concentrations of FFA the inhibition of adenylyl cyclase by adenosine and the removal of cAMP by the action of phosphodiesterase. ACTFI,TSFI, and glucagon may not activate adenylyl cyclase in vivo, since the concentration of each hormone required in vitro is much higher than is found in the circulation. Positive ( ) and negative ( ) regulatory effects are represented by broken lines and substrate flow by solid lines.

The major types of adipose tissue are (1) white adipose tissue, which manufactures, stores, and releases lipid and (2) brown adipose tissue, which dissipates energy via uncoupled mitochondrial respiration. Obesity research includes evaluation of the activity of adrenergic receptors and their effect on adipose tissue with respect to energy storage and expenditure or thermogenesis. 

In capillaries of adipose tissue (and muscle), apoC-II activates lipoprotein lipase, the fetty adds released enter the tissue for storage, and the glycerol is retrieved by the liver, which has glycerol kinase. The chylomicron remnant is picked up by hepatocytes through the apoE receptor thus, dietary cholesterol, as well as any remaining triglyceride, is released in the hepatocyte. 

The lipid metabolism of adipose tissue is also influenced by the hormone. In these cells, insulin stimulates the reorganization of glucose into fatty acids. This is mainly based on activation of acetyl CoA carboxylase (see p. 162) and increased availability of NADPH+H due to increased PPP activity (see p. 152). On the other hand, insulin also inhibits the degradation of fat by hormone-... 

Il.f.l.1. Insulins. Insulin is the most effective of diabetes medications. Insulin has profound effects on carbohydrate, protein, fat metabolism and electrolytes. It has anabolic and anticatabolic actions. In a state of insulin deficiency, glycogenesis, glucose transport, protein synthesis, triglyceride synthesis, LPL activity in adipose tissue, cellular potassium uptake all decrease on the other hand, gluconeogene-sis, glycogenolysis, protein degradation, ketogene-sis, lipolysis increase. 

Many enzymes are regulated by covalent modification, most frequently by the addition or removal of phosphate groups from specific serine, threonine, or tyrosine residues of the enzyme. In the fed state, most of the enzymes regulated by covalent modification are in Ihe dephosphorylated form and are active (see Figure 24.2). Three exceptions are glycogen phosphorylase (see p. 129), fructose bis-phosphate phosphatase-2 (see p. 98), and hormone-sensitive lipase of adipose tissue (see p. 187), which are inactive in their dephosphorylated state. 

Chylomicrons transport dietary triacylglycerol and cholesteryl ester from the intestine to other tissues in the body. Very-low-density lipoprotein functions in a manner similar to the transport of endogenously made lipid from the liver to other tissues. These two types of triacylglycerol-rich particles are initially degraded by the action of lipoprotein lipase, an extracellular enzyme that is most active within the capillaries of adipose tissue, cardiac and skeletal muscle, and the lactating mammary gland. Lipoprotein lipase catalyzes the hydrolysis of triacylglycerols (see fig. 18.3). The enzyme is specifically activated by apoprotein C-II, which... 

Topiramate, felbamate, and zonisamide are associated with weight loss. In animals topiramate reduced food intake, but also reduced energy disposition in the absence of reduced intake. In addition, topiramate increased lipoprotein lipase activity in adipose tissue, possibly reflecting enhanced regulatory thermogenesis. In humans and animals topiramate reduces leptin concentrations. With felbamate weight loss is almost always associated with... 

In six patients with renal transplants treated with sirolimus, mean total plasma cholesterol, triglyceride, and apolipoprotein concentrations increased (1067). The authors suggested that sirolimus increases lipase activity in adipose tissue and reduces lipoprotein lipase activity, resulting in increased hepatic synthesis of triglycerides, increased secretion of VLDL, and increased hypertriglyceridemia. 

CM and VLDL secreted by intestinal cells and VLDL synthesized and secreted in the liver have similar metabolic fates. After secretion into the blood, newly formed CM and VLDL take up apoprotein (apo-C) from HDL and are subsequently removed from the blood (plasma half-life of less than 1 h in humans [137]) primarily by the action of lipoprotein lipase (LPL). Lipoprotein lipase is situated mainly in the vascular bed of the heart, skeletal muscle, and adipose tissue and catalyzes the breakdown of core TG to monoglycerides and free fatty acids, which are taken up into adjacent cells or recirculated in blood bound to albumin. The activity of LPL in the heart and skeletal muscle is inversely correlated with its activity in adipose tissue and is regulated by various hormones. Thus, in the fasted state, TG in CM and VLDL is preferentially delivered to the heart and skeletal muscle under the influence of adrenaline and glucagon, whereas in the fed state, insulin enhances LPL activity in adipose tissue, resulting in preferential uptake of TG into adipose tissue for storage as fat. 

Brewster DW, Matsumura F. 1988. Reduction of adipose tissue lipoprotein lipase activity as a result of in vivo administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin to the guinea pig. Biochem Pharmacol 37 2247-2253. 

Hamosh, M., Clary, T.R., Chernick, W.W., Scow, R.O. 1970. Lipoprotein lipase activity of adipose and mammary tissue and plasma triglyceride in pregnant and lactating rats. Biochim. Biophys. Acta 210, 473 182. 

Recent advances in molecular and cell biology have shown that adipose tissue not only stores excess energy in the form of fat, but also secretes physiologically active substances called adipocytokines (Matsuzawa et al., 1999). In obesity, adipocytes (cells of adipose tissues) are increased and enlarged, and they secrete excessive amounts of inflammatory adipocytokines, such as tumor necrosis factor-alpha (Hotamisligil et al., 1993) and monocyte chemoattractant protein-1 (Sartipy and Loskutoff, 2003). This induces type-2 diabetes, such as... 

In the capillaries of adipose tissue and muscle, fatty acids of chylomicrons are removed from the triacylglycerols hy the action of lipoprotein lipase (LPL) LPL is present on the surface of the endothehal cells of the capillaries. Chylomicron apo-C-II activates LPL in the presence of phospholipid. 

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