Combination of fish oil and fish protein hydrolysate reduces the plasma cholesterol level with a concurrent increase in hepatic cholesterol level in high-fat-fed Wistar rats

Nutrition. 2009 Jan;25(1):98-104. doi: 10.1016/j.nut.2008.07.005. Epub 2008 Aug 26.


Objective: This study investigated the potential additive or synergistic effect of fish oil (FO) and fish protein hydrolysate (FPH) on cholesterol concentration in plasma and the liver.

Methods: Male Wistar rats were fed high-fat diets (30% fat, 20% protein, wt/wt) containing FO (5%), FPH (10%), a combination of FO and FPH, or a high-fat control diet. After 7 wk of feeding, the rats were fasted for 12 h before lipid levels in plasma and the liver and hepatic activities of acyl-coenzyme A:cholesterol acyltransferase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and fatty acid synthase were measured.

Results: The combination of FO and FPH in the diet profoundly reduced the plasma cholesterol level, mainly due to lowering of high-density lipoprotein cholesterol, whereas the hepatic total cholesterol concentration was elevated compared with control rats and rats fed diets containing FPH or FO alone. The elevated cholesterol concentration in the liver was caused by an increased amount of cholesteryl esters and was in correlation to an increased activity of acyl-coenzyme A:cholesterol acyltransferase. There was a reduced fatty acid synthase activity that could lead to a reduced lipogenesis in the rats fed a combination of FO and FPH.

Conclusion: A dietary combination of FO and FPH resulted in lower levels of plasma cholesterol and higher levels of hepatic cholesterol compared with dietary FO or FPH alone. Further studies are warranted to confirm whether the hypocholesterolemic effect was due to a reduced secretion of very low-density lipoprotein from the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Coenzyme A / metabolism
  • Animals
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / pharmacology*
  • Cholesterol / blood
  • Cholesterol / metabolism*
  • Drug Synergism
  • Fatty Acid Synthases / metabolism
  • Fish Oils / administration & dosage
  • Fish Oils / pharmacology*
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • Lipid Metabolism / drug effects*
  • Lipid Metabolism / physiology
  • Liver / enzymology
  • Liver / metabolism*
  • Male
  • Protein Hydrolysates / administration & dosage
  • Protein Hydrolysates / pharmacology*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Sterol O-Acyltransferase / metabolism


  • Acyl Coenzyme A
  • Anticholesteremic Agents
  • Fish Oils
  • Protein Hydrolysates
  • Cholesterol
  • Hydroxymethylglutaryl CoA Reductases
  • Sterol O-Acyltransferase
  • Fatty Acid Synthases