Pathogenic role of abnormal fatty acids and adipokines in the portal flow. Relevance for metabolic syndrome, hepatic steatosis and steatohepatitis.
Evidence has been provided that increased levels of non esterified fatty acids (NEFA) in the portal flow would produce insulin resistance and would also stimulate the hepatic protein synthesis, thereby explaining the increased plasma levels not only of apolipoprotein B, but also of other liver-derived enzymes and proteins occurring in overweight and hypertriglyceridemic patients. The high plasma concentration of triglyceride-rich lipoprotein would facilitate the transfer of cholesteryl esters from HDL and LDL to VLDL in exchange for triglycerides, a process mediated by liver-derived cholesteryl ester transfer protein (CETP). The triglyceride thereby acquired in HDL and LDL would then be hydrolyzed by hepatic lipase. The resulting association of increased triglycerides, low HDL cholesterol and small dense LDL is considered to be an atherogenic profile. The prothrombotic state, another feature of the metabolic syndrome, may also be explained by an enhanced hepatic synthesis of clotting factors and of the inhibitors of fibrinolysis. It was recently shown that adipocyte synthesized adiponectin reduces the release of fatty acids from the adipose tissue and would also enhance their uptake and oxidation in the muscle, thereby limiting their uptake in the liver. Decreased adiponectin production in obesity would therefore promote the development of insulin resistance, of atherogenic dyslipidemia and of the prothrombotic state. Because adiponectin also exerts an antiinflammatory activity by antagonizing TNFalpha, hypoadiponectinemia may be involved in atherogenesis and in the progression of hepatic steatosis to steatohepatitis.
Brudaşcă
Ioana
I
Department of Clinical Biochemistry, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. ioanabrudasca@yahoo.com
Cucuianu
M
M
D054392:Adipokines / Q000378:metabolism; D000273:Adipose Tissue / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005234:Fatty Liver / Q000503:physiopathology; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D024821:Metabolic Syndrome / Q000503:physiopathology; D011168:Portal System / Q000503:physiopathology*
D054392:Adipokines; D005230:Fatty Acids, Nonesterified; D008074:Lipoproteins