Adipose tissue, lipoprotein lipase

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. 

Chylomicrons are triglyceride rich and contain apolipoprotein B-48 and the A types. The latter are synthesized in the intestinal tract cells. Additional apoproteins are transferred to the chylomicrons from HDL in circulation the apoE and apoC types. Their site of synthesis is the liver. The chylomicrons are subject to degradation by lipoprotein lipase in the peripheral tissue, especially adipose tissue. Lipoprotein lipase activity is increased by increased blood insulin levels. This enzyme is extracellular, attached to the capillary endothelial cells, and activated by ApoC-II, which is present in the chylomicrons. Lipoprotein lipase causes the hydrolysis of triglycerides, thus decreasing chylomicron size... 

GIP stimulates insulin secretion only in the presence of mild to moderate hyperglycaemia (Andersen et al., 1978 Wahl et al., 1992), but not in the presence of normal glucose concentrations. In addition to secretion of insulin, GIP augments insulin-dependent inhibition of hepatic glycogenolysis (Elahi et al., 1986 Hartman et al., 1986). It also activates adipose tissue lipoprotein lipase (Eckel et al., 1978) and has been shown to stimulate fatty acid synthesis de novo in rat adipose tissue (Oben et al., 1991). 

S. Reynisdottir, B. Angelin, and D. Langin, et al.. Adipose tissue lipoprotein lipase and hormone-sensitive lipase. Contrasting findings in familial combined hyperlipidemia and insulin resistance syndrome, Arterioscler. Thromh. Vase. 

P.H. Weinstock, S. Levak-Frank, and L. C. Hudgins, et al.. Lipoprotein lipase controls fatty acid entry into adipose tissue, but fat mass is preserved by endogenous synthesis in mice deficient in adipose tissue lipoprotein lipase, Proc. Natl. Acad. Sci. USA, 1997, 94, 10261-10266. 

Maheux P, et al. Relationship between insulin-mediated glucose disposal and regulation of plasma and adipose tissue lipoprotein lipase. Diabetolo-gia 1997 40 850-858. 

F30. Fried, S. K., and Zechner, R. Cachectin/tumor necrosis factor decreases human adipose tissue lipoprotein lipase mRNA levels, synthesis, and activity. J. Lipid Res. 30, 1917-1923 (1989). 

Kem PA, Ong JM, Bahman S, Carty J. The effects of weight loss on the activity and expression of adipose-tissue lipoprotein lipase in very obese humans. N Engl J Med 1990 322 1053-1059. 

To throw some light upon mechanisms by which dietary fiber could influence plasma lipoproteins, heart and adipose tissue lipoprotein lipase activities were measured after feeding some of the dietary fiber containing diets. This key enzyme in lipoprotein metabolism is one of the most important factors determining plasma triglyceride and plasma HDL concentrations (16). 

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. 

The hypertriglyceridemia of Type II diabetes, unlike that which is found with Type I diabetes, is not due to excessive adipocyte lipolysis. This is because only a small level of insulin action is required to suppress excessive adipose tissue hormone-sensitive lipase activity. In Type II diabetes, there is insufficient adipose tissue lipoprotein lipase and excessive hepatic triglyceride synthesis. Thus, inefficient VLDL triglyceride catabolism and excessive VLDL triglyceride secretion both contribute to the excess VLDL in Type II diabetes. 

Lipoprotein lipase (LPL) Local enzymatic Endothelial cells within adipose tissue Lipoprotein-triglyceride hydrolysis... 

The rdle of adipose tissue glyceride lipase in regulating plasma FFA levels, liver TG and plasma lipoprotein-bound lipids has prompted the investigation of drugs interfering with the activation of the lipolytic enzyme, by acting directly on it or by inhibiting the formation of cyclic 3, S -AMP in adipose tissue. 

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 27-1. Metabolic interrelationships between adipose tissue, the liver, and extrahepatic tissues. In extrahepatic tissues such as heart, metabolic fuels are oxidized in the following order of preference (1) ketone bodies, (2) fatty acids, (3) glucose. (LPL, lipoprotein lipase FFA, free fatty acids VLDL, very low density lipoproteins.)...

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 Storage and breakdown of triacylglyc-erol Esterification of fatty acids and lipolysis lipogenesis Glucose, lipoprotein triacylglycerol Free fatty acids, glycerol Lipoprotein lipase, hormone-sensitive lipase... 

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. 

High-density lipoproteins (HDL) and very low-density lipoproteins (VLDL) are synthesized in the liver. LDL is produced in the blood stream as VLDL particles are partially delipidated by lipoprotein lipase, a triglyceride hydrolysing enzyme located on the luminal surface of vessels in sites such adipose tissue. 

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 metabolism of VLDL is very similar to that of chylomicrons, the major difference being that VLDL are assembled in hepatocytes to transport triglyceride containing fatty acids newly synthesized from excess glucose, or retrieved from the chylomicron remnants, to adipose tissue and musde. ApoB-100 is added in the hepatocytes to mediate release into the blood. Like chylomicrons, VLDL acquire apoC-II and apoE from HDL in the blood, and are metabolized by lipoprotein lipase in adipose tissue and musde. 

Figure 7.3 The action of lipoprotein lipase in the hydrolysis of triacylglycerol in the blood and the fate of the fatty adds produced. Lipoprotein Lipase is attached to the luminal surface of the capillaries in the tissues that are responsible for removal of triacylglycerol from the bloodstream (e.g. adipose tissue, muscle, lactating mammary gland).

Current available information does not permit definitive conclusions on the nature, specificity, and mechanism of action of the protein cofactor (s) of lipoprotein lipase. It is verj difiicult to correlate the observations described above (summarized in Table 10) since the enzyme preparations used were not pure or well characterized, and were derived from various sources. For instance, two species of lipoprotein lipase have been reported to exist in rat adipose tissue (G4), and major differences between enzymes of liver and adipose tissue have been noted (G16). Also, the nature of the apoprotein preparations employed as protein cofactor (s) of lipoprotein lipase has not been clearly specified in all the studies contaminated materials may account for the spurious results observed. At present, it is not known how apoproteins such as apo Glu, apo Ala, and apo Ser could exhibit their activator or inhibitor activity on lipoprotein lipase. If these different apoproteins indeed prove to be cofactors for lipoprotein lipase, the nature of the lipid-protein specificity must be established and thus the role played by carbohydrates, since some of these apoproteins are glycoproteins. 

G2. Ganesan, D., Bradford, R. H., Alaupovic, P., and McConathy, W. J., Differential activation of lipoprotein lipase form human post-heparin plasma, milk and adipose tissue by polypeptides of human serum apolipoprotein C. FEBS (Fed. Eur. Biochem. Soc.), Lett. 15, 205-208 (1971). 

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