Naringenin decreases progression of atherosclerosis by improving dyslipidemia in high-fat-fed low-density lipoprotein receptor-null mice.

Abstract

OBJECTIVE:

Naringenin is a citrus flavonoid that potently inhibits the assembly and secretion of apolipoprotein B100-containing lipoproteins in cultured hepatocytes and improves the dyslipidemia and insulin resistance in a mouse model of the metabolic syndrome. In the present study, we used low-density lipoprotein receptor-null mice fed a high-fat diet (Western, TD96125) to test the hypothesis that naringenin prevents atherosclerosis.

METHODS AND RESULTS:

Three groups (chow, Western, and Western plus naringenin) were fed ad libitum for 6 months. The Western diet increased fasting plasma triglyceride (TG) (5-fold) and cholesterol (8-fold) levels compared with chow, whereas the addition of naringenin significantly decreased both lipids by 50%. The Western-fed mice developed extensive atherosclerosis in the aortic sinus because plaque area was increased by 10-fold compared with chow-fed animals. Quantitation of fat-soluble dye (Sudan IV)-stained aortas, prepared en face, revealed that Western-fed mice also had a 10-fold increase in plaque deposits throughout the arch and in the abdominal sections of the aorta, compared with chow. Atherosclerosis in both areas was significantly decreased by more than 70% in naringenin-treated mice. Consistent with quantitation of aortic lesions, the Western-fed mice had a significant 6-fold increase in cholesterol and a 4-fold increase in TG deposition in the aorta compared with chow-fed mice. Both were reduced more than 50% by naringenin. The Western diet induced extensive hepatic steatosis, with a 10-fold increase in both TG and cholesteryl ester mass compared with chow. The addition of naringenin decreased both liver TG and cholesteryl ester mass by 80%. The hyperinsulinemia and obesity that developed in Western-fed mice was normalized by naringenin to levels observed in chow-fed mice.

CONCLUSIONS:

These in vivo studies demonstrate that the citrus flavonoid naringenin ameliorates the dyslipidemia in Western-fed low-density lipoprotein receptor-null mice, leading to decreased atherosclerosis; and suggests a potential therapeutic strategy for the hyperlipidemia and increased risk of atherosclerosis associated with insulin resistance.

• Authors: Erin E Mulvihill, Julia M Assini, Brian G Sutherland, Alessandra S DiMattia, Maryam Khami, Julie B Koppes, Cynthia G Sawyez, Stewart C Whitman, Murray W Huff
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 30 Issue 4 Pg. 742-8 (Apr 2010) ISSN: 1524-4636 [Electronic] United States
• PMID: 20110573 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Fats
• Flavanones
• Hypolipidemic Agents
• Receptors, LDL
• Triglycerides
• Cholesterol
• naringenin

Topics

• Animals
• Aorta (drug effects, metabolism, pathology)
• Aortic Diseases (etiology, metabolism, pathology, prevention & control)
• Atherosclerosis (etiology, metabolism, pathology, prevention & control)
• Cholesterol (metabolism)
• Diet, Atherogenic
• Dietary Fats
• Disease Models, Animal
• Disease Progression
• Fatty Liver (etiology, prevention & control)
• Flavanones (pharmacology)
• Hyperinsulinism (etiology, prevention & control)
• Hyperlipidemias (drug therapy, etiology, metabolism, pathology)
• Hypolipidemic Agents (pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Obesity (etiology, prevention & control)
• Receptors, LDL (deficiency, genetics)
• Time Factors
• Triglycerides (metabolism)