Atorvastatin Treatment Induced Peroxisome Proliferator-Activated Receptor α Expression and Decreased Plasma Nonesterified Fatty Acids and Liver Triglyceride in Fructose-Fed Rats

Abstract

We aimed to investigate the effect of atorvastatin (5 and 30 mg/kg/day for 2 weeks) on hepatic lipid metabolism in a well established model of dietary hypertriglyceridemia, the fructosefed rat. Fructose feeding (10% fructose in drinking water for 2 weeks) induced hepatic lipogenesis and reduced peroxisome proliferator-activated receptor ␣ (PPAR␣) expression and fatty acid oxidation. As a result, plasma and liver triglyceride and plasma apolipoprotein B (apoB) levels were increased. Atorvastatin, 5 and 30 mg/kg during 2 weeks, markedly reduced plasma triglyceride, but decreased apoB levels only at the highest dose tested (50%). Triglyceride biosynthetic enzymes and microsomal triglyceride transfer protein were unchanged, whereas liver PPAR␣, acyl-CoA oxidase, and carnitine palmitoyltransferase I mRNA levels (1.9-, 1.25-, and 3.4-fold, respectively) and hepatic fatty acid ␤-oxidation activity (1.25-fold) were increased by atorvastatin at 30 mg/kg. Furthermore, hepatic triglyceride content (45%) and plasma nonesterified fatty acids (NEFAs) (49%) were reduced. These results show for the first time that liver triglyceride increase in fructose-fed rats is linked to decreased expression of PPAR␣, which is prevented by atorvastatin treatment. The increase in PPAR␣ expression caused by atorvastatin was associated with reduced liver triglyceride and plasma NEFA levels.

Regulation of Skeletal Muscle Peroxisome Proliferator-Activated Receptor .GAMMA. Expression by Exercise and Angiotensin-Converting Enzyme Inhibition in Fructose-Fed Hypertensive Rats

“…Although we did not measure the mechanics of fatty acid circulation in the present study, the circulating level of plasma FFA depends on the lipolysis of circulating lipoproteins, the rate of FFA release from adipose tissue, and the rate at which these fatty acids are taken up and reesterified by tissues (52). According to the fatty acid stealing hypothesis (53), PPARγ may act to promote the movement of FFA into skeletal muscle and other tissues having a high level of PPARγ (54).…”

Serum Cholesterol and Statin Use Predict Virological Response to Peginterferon and Ribavirin Therapy†,‡

“…34,35 Several studies have shown that statins increase PPARa expression in vitro and in vivo and induce transcriptional activity. [36][37][38] Limiting the development of drug resistance in the era of directly acting antiviral therapies will be critical. This will likely involve synergy with other compounds demonstrating antiviral activity.…”

Suppressor of cytokine signaling-3 (SOCS-3) and a deficit of serine/threonine (Ser/Thr) phosphoproteins involved in leptin transduction mediate the effect of fructose on rat liver lipid metabolism

“…The relative levels of specific messenger RNAs (mRNAs) were assessed by reversetranscription polymerase chain reaction, as described. 13 Adenosyl phosphoribosyl transferase was used as an internal control. The number of cycles, primer sequences, and resulting polymerase chain reaction products are listed in Table 1.…”