[Free fatty acids: mediators of insulin resistance and atherosclerosis].
Free fatty acids (FFAs) are involved in the transportation of energy; in the postprandial phase to the peripheral tissues and in the postabsorptive phase from the adipose tissue to the liver. In the postprandial phase, FFAs are mainly derived from hydrolysis of triglyceride-rich particles like chylomicrons and very low-density lipoproteins (VLDL). The flux of FFAs is directed to peripheral cells such as adipocytes and muscle cells. In the postabsorptive period, FFAs are transported to the liver after being released from intracellular storage in the adipocytes. Complement component 3 (C3) plays an important role in the uptake of free fatty acids by the peripheral cells and their esterification to triglycerides. Since C3 is also involved in the pathogenesis of the insulin resistance syndrome, and since a deviant FFA metabolism with an increased FFA flux to the liver may induce insulin resistance, it is hypothesized that C3 may form the missing link between FFA metabolism and insulin resistance. In addition, recent studies have increasingly indicated that atherosclerosis is in fact an inflammation-based process involving complement-dependent responses, in which FFAs seem to play a role in the complement-dependent pathway. It has recently become apparent that FFAs have a regulatory function in the transcription of DNA, in relation to lipoprotein metabolism. This is where PPAR-gamma and PPAR-alpha agonists ('glitazones' and fibrates respectively) are active (PPAR is an abbreviation for peroxisome proliferation activating receptor). Glitazons may play an important role in the treatment of insulin resistance and related disorders. Acquiring more knowledge about the relationship between complement and FFA metabolism may increase our understanding of these processes and provide openings for the development of new antiatherogenic strategies.
Castro Cabezas
M
M
Afd. Vasculaire Geneeskunde, Universitair Medisch Centrum Utrecht, Postbus 85.500, 3508 GA Utrecht. m.castrocabezas@azu.nl
Erkelens
D W
DW
van Dijk
H
H
D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D003176:Complement C3 / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D008074:Lipoproteins / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D013844:Thiazoles / Q000494:pharmacology*; D014157:Transcription Factors / Q000819:agonists; D014280:Triglycerides / Q000096:biosynthesis
D003176:Complement C3; D005230:Fatty Acids, Nonesterified; D008074:Lipoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D014157:Transcription Factors; D014280:Triglycerides