Affiliation:
1. Department of Medicine, University of California, San Francisco 94143; Metabolism Section, Medical Service, Department of Veterans Affairs Medical Center, San Francisco, California 94121; and
2. Ross Products Division, Abbott Laboratories, Columbus, Ohio 43215
Abstract
Acyl-CoA synthetase (ACS) catalyzes the activation of fatty acids (FA) to acyl-CoA esters, which are further metabolized in either anabolic or catabolic pathways. Endotoxin [lipopolysaccharide (LPS)], tumor necrosis factor (TNF), and interleukin-1 (IL-1) enhance hepatic FA synthesis and reesterification and inhibit FA oxidation. LPS also decreases triglyceride storage in adipose tissue and inhibits the uptake of FA by heart and muscle. Therefore, in this study we examined the effects of LPS and cytokines on ACS (now also known as ACS1) mRNA expression and activity in multiple tissues in Syrian hamsters. LPS markedly decreased ACS1 mRNA levels in liver, adipose tissue, heart, and skeletal muscle. The inhibitory effects of LPS on ACS1 mRNA levels in liver and adipose tissue were observed as early as 2–4 h after administration, became maximal by 4–8 h, and were sustained for ≥24 h. Very low doses of LPS (0.1–1 μg/100 g body wt) were needed to reduce ACS1 mRNA levels in liver and adipose tissue. TNF and IL-1 mimicked the effect of LPS on ACS1 mRNA levels in liver and adipose tissue. LPS decreased ACS activity in adipose tissue, heart, and muscle. In liver, where ACS is localized in several subcellular organelles, both LPS and cytokines decreased mitochondrial ACS activity, whereas they increased microsomal ACS activity. Taken together, these results indicate that LPS and cytokines decrease ACS1 mRNA expression and ACS activity in tissues where FA uptake and/or oxidation is decreased during sepsis. In liver, where FA oxidation is decreased during sepsis but the reesterification of FA is increased, LPS and cytokines decrease ACS1 mRNA and mitochondrial ACS activity, which may inhibit FA oxidation, but increase microsomal ACS activity, which may support the reesterification of peripherally derived FA for triglyceride synthesis.
Publisher
American Physiological Society
Subject
Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism
Cited by
49 articles.
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