Dietary polyunsaturated fatty acids enhance hepatic AMP-activated protein kinase activity in rats

https://doi.org/10.1016/j.bbrc.2004.11.114Get rights and content

Abstract

Polyunsaturated fatty acids (PUFA) and a number of drugs (metformin, thiazolidinediones) and hormones (leptin, adiponectin) that activate AMP-activated protein kinase (AMPK) have been reported to improve insulin sensitivity. To determine whether PUFA activate AMPK, Sprague–Dawley rats were adapted to a 3 h meal-feeding regimen using a fat-free diet (FFD) supplemented with fish oil (n  3) or triolein (n  9) for 7 days. No differences in hepatic AMPK activity were observed between the groups after 21 h of fasting. On the other hand, hepatic AMPK phosphorylation was decreased in rats refed the FFD, the FFD + triolein, and the FFD + PUFA by 80%, 75%, and 50%, respectively, when assessed 2 h after completion of a meal. In keeping with these changes, decreases in acetyl-CoA carboxylase phosphorylation and carnitine palmitoyl transferase-1 mRNA and increases in fatty acid synthase gene expression were greatest in rats fed the FFD and least in the PUFA-fed rats. The results indicate that dietary PUFA enhance hepatic AMPK activity in vivo, and implicate AMPK as a component of the nutrient-sensing mechanism through which dietary fatty acids and especially PUFA influence the regulation of hepatic lipid metabolism and gene expression.

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Materials and methods

All animal studies were approved by the Institutional Animal Care and Use Committee of the Pennington Biomedical Research Center. Male Sprague–Dawley rats (Harlan Sprague–Dawley, Indianapolis, IN; 120–130 g) were housed in a temperature- and light-controlled environment, and adapted to a 3 h per day (09:00–12:00) meal-feeding regimen using a high-glucose, fat-free diet (80% dextrose) formulated according to AIN-93-G diet (Dyets; Bethlehem, PA). After a 7-day adaptation period, the rats were

Effect of a high-glucose meal on AMPK and ACC phosphorylation, AMPK activity, and FAS and CPT-1 mRNA

Rats were trained for 7 days to consume a high-glucose, fat-free diet during a single daily meal of 3 h duration (09:00–12:00 AM). AMPK activity and phosphorylation were assayed prior to the meal (21 h fasting) and 5 h after the food was introduced. As shown in Figs. 1A and C, the ingestion of high-glucose diet decreased the phosphorylation of AMPK by 80% from its pre-meal value, whereas AMPK protein abundance was unchanged. The decrease in P-AMPK was associated with a concomitant reduction in

Discussion

The results suggest that the ingestion of PUFA causes changes in AMPK activity that could account for PUFA’s previously described effects on hepatic lipid metabolism and gene expression. Thus, the ingestion of a meal enriched in PUFA resulted in a much smaller decrease in AMPK phosphorylation and activity than did comparable glucose-rich meals or a glucose-rich meal supplemented with triolein. In addition, changes in ACC phosphorylation and FAS and CPT-1 mRNA abundance in the latter groups were

Acknowledgments

The authors thank Amanda K. Shirah and Xiaochun Xi for their technical assistance and Dr. A. Zuberi for critical reading of the manuscript. This work was supported by NIH Grants RO1 DK 053872 (T.W.G.), DK 064156 (T.W.G.), DK 19514 (N.B.R.), DK 49147 (N.B.R.), and a grant from the Juvenile Diabetes Foundation (N.B.R.).

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