Cholesterol Transport

Two distinct sources and responsible mechanisms for free cholesterol released from adipocytes during lipolysis can be envisioned, cholesterylesters embedded in the TAG core of LD and cleaved by activated HSL, which exerts pronounced cho-lesterylesterase activity, and unesterified cholesterol intercalated into the phospho-lipid monolayer surrounding the TAG core of LD, which may be liberated simply during reduction of the LD surface upon TAG hydrolysis by activated HSL. Thus, for both mechanisms HSL may be rate-limiting for cholesterol release from adipo-cytes, which consequently would proceed in parallel to mobilization of FA and glycerol from TAG. However, when evaluating the concomitant release of glycerol and cholesterol from 3T3-L1 adipocytes treated with isoproterenol, cholesterol efflux in the medium did not occur during the first 4 h of lipolytic stimulation

[319]. A more prolonged lipolytic stimulus (24 h treatment with monobutyryl-cAMP) released significant amounts of cholesterol into the medium. This suggests that prolonged lipolysis (i.e. long-term fasting period) is required for adipo-cyte cholesterol to re-enter the plasma in vivo, and that release of cholesterol from adipocytes is regulated, most likely, by its transport across the plasma membrane in addition to HSL activity. The question of the link between the process of TAG and cholesterol mobilization from adipocytes during lipolysis has received fresh attention since the identification of the ABCA1 protein pathway, which is a key mediator of cellular cholesterol efflux [320]. The reported expression of ABCA1 in adipocytes may be controlled by LXR, which is highly expressed and acts as key transcriptional regulator of ABCA1 in adipocytes [321, 322]. Intracellular cAMP stimulates cholesterol efflux in macrophages by acting through ABCA1 [323]. Thus, TAG mobilization and cholesterol efflux through ABCA1 in adipocytes might be linked.

278 11 Physiological and Pharmacological Regulation of Triacylglycerol Storage and Mobilization 11.4

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    What is a TAG in cholesterol transport?
    8 years ago

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