title: Lipoteichoic acid stimulates lipolysis and hepatic triglyceride secretion in rats in vivo.
abstract: The host response to infection is frequently accompanied by changes in lipid metabolism. Previous studies have shown that endotoxin (LPS), a component of the cell wall of gram-negative bacteria, increases serum lipid levels. In this study, we demonstrate that lipoteichoic acid (LTA), a component of the cell membrane of gram-positive bacteria, also increases serum lipid levels in rats in a dose-dependent manner (0.1-300 micrograms/200 g body weight). Serum triglyceride levels increased within 2 h after LTA administration with peak values at 4 h (2-fold increase). Serum cholesterol levels also increased but the effect was delayed occurring at 16 h and was relatively small (1.2-fold increase). LTA (10 micrograms/200 g BW) did not decrease adipose tissue lipoprotein lipase activity or the clearance of triglyceride-rich lipoproteins. Rather, the LTA-induced hypertriglyceridemia is due to an increase in hepatic triglyceride secretion. LTA stimulates both hepatic de novo fatty acid synthesis and lipolysis. The increased delivery of free fatty acids to the liver plays a major role in the LTA-induced hypertriglyceridemia. Pretreatment with phentolamine, an alpha-adrenergic receptor antagonist, and alprenolol, a beta-adrenergic receptor antagonist, or phentolamine alone significantly suppressed the hypertriglyceridemia induced by LTA. These adrenergic inhibitors had no significant effect on the increase in lipolysis. These results indicate that catecholamines are involved in mediating the LTA-induced increase in hepatic triglyceride secretion via alpha-adrenergic receptors. These changes in lipid metabolism may play an important role in the organism's response to gram-positive infection.
authors.affiliation: Department of Medicine, University of California, San Francisco, 94143, USA.
authors.forename: K
authors.initials: K
authors.lastname: Nonogaki
authors.forename: A H
authors.initials: AH
authors.lastname: Moser
authors.forename: X M
authors.initials: XM
authors.lastname: Pan
authors.forename: I
authors.initials: I
authors.lastname: Staprans
authors.forename: C
authors.initials: C
authors.lastname: Grunfeld
authors.forename: K R
authors.initials: KR
authors.lastname: Feingold
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D002784:Cholesterol / Q000097:blood; D002914:Chylomicrons / Q000378:metabolism; D015228:Hypertriglyceridemia / Q000139:chemically induced; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008071:Lipoprotein Lipase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013682:Teichoic Acids / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002914:Chylomicrons; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D014280:Triglycerides; C009900:lipoteichoic acid; D000526:Alprenolol; D002784:Cholesterol; D008071:Lipoprotein Lipase; D010646:Phentolamine