Biochemistry and pathophysiology of intravascular and intracellular lipolysis

Abstract

All organisms use fatty acids (FAs) for energy substrates and as precursors for membrane and signaling lipids. The most efficient way to transport and store FAs is in the form of triglycerides (TGs); however, TGs are not capable of traversing biological membranes and therefore need to be cleaved by TG hydrolases (“lipases”) before moving in or out of cells. This biochemical process is generally called “lipolysis.” Intravascular lipolysis degrades lipoprotein-associated TGs to FAs for their subsequent uptake by parenchymal cells, whereas intracellular lipolysis generates FAs and glycerol for their release (in the case of white adipose tissue) or use by cells (in the case of other tissues). Although the importance of lipolysis has been recognized for decades, many of the key proteins involved in lipolysis have been uncovered only recently. Important new developments include the discovery of glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), the molecule that moves lipoprotein lipase from the interstitial spaces to the capillary lumen, and the discovery of adipose triglyceride lipase (ATGL) and comparative gene identification-58 (CGI-58) as crucial molecules in the hydrolysis of TGs within cells. This review summarizes current views of lipolysis and highlights the relevance of this process to human disease.

Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing

“… Catecholamine-induced lipolysis, the first step in generation of energy substrates through hydrolysis of triglycerides (TGs) 1 , declines with age 2,3 . The defect in mobilization of free fatty acids (FFA) in elderly is accompanied with increased visceral adiposity, lower exercise capacity, failure to maintain core body temperature during cold stress, and reduced ability to survive starvation.…”

ABCA1 in adipocytes regulates adipose tissue lipid content, glucose tolerance, and insulin sensitivity

“…However, in order to cross the adipocyte plasma membrane and be released into the plasma, adipocyte TGs must be hydrolyzed into fatty acids by a process known as lipolysis ( 6 ).…”

“…Cholesterol and TGs are taken up by adipocytes from plasma lipoproteins via lipoprotein receptors including the LDL receptor (LDLR), scavenger receptor B1 (SR-B1), and CD36 (3)(4)(5). TGs leave adipose tissue as NEFAs after TG lipolysis ( 6 ), while cholesterol is removed from adipocytes via transporters such as ABCA1 and ABCG1 ( 7,8 ).…”

Imaging Modalities for Triglyceride Deposit Cardiomyovasculopathy

“…In addition, it has no direct relationship with Annals of Nuclear Cardiology J-STAGE Advance published date: August 23, 2017 doi: 10.17996/anc. [17][18][19][20][21][22][23][24][25][26][27][28] plasma TG levels, because regulatory mechanism and responsible enzymes are different intracellularly from those in plasma (7). The probands for TGCV carried genetic mutations in the adipose triglyceride lipase (ATGL), which is the ratelimiting enzyme for hydrolysis of intracellular TG (8).…”