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Carbohydrate restriction reduces hepatic cholesterol accumulation and acyl CoA cholesteryl acyltransferase (ACAT) activity induced by high levels of dietary cholesterol
Author(s) -
TorresGonzalez Moises,
Volek Jeff S,
Freake Hedley C,
Fernandez Maria Luz
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a101
Subject(s) - sterol o acyltransferase , cholesterol , medicine , chemistry , endocrinology , carbohydrate , cholesteryl ester , enzyme , biochemistry , biology , lipoprotein
Male guinea pigs (n=10/group) were fed a diet containing 42% energy from carbohydrate (CHO) and 0.04% cholesterol (control), a diet with the same concentration of CHO and 0.25% cholesterol (HCHO) or a CHO restricted (CR) diet with 11% of energy from CHO and 0.25% cholesterol for 12 wk. Hepatic lipids and ACAT activity were determined. The main effects of dietary cholesterol were observed in free cholesterol (FC) and triglycerides (P< 0.05). High cholesterol in the diet resulted in higher levels of FC and triglycerides compared with the controls. In contrast carbohydrate restriction significantly affected total and cholesterol ester (CE) concentrations as well as ACAT activity. CE was lower in the CR (2.91 ± 1.37 mg/g) compared with the HCHO (4.31 ± 1.5 mg/g). The concentration of total cholesterol was also lower in the CR (9.56 ± 1.44 mg/g) than in the HCHO group (11.68 ± 1.70 mg/g). ACAT activity, the regulatory enzyme of cholesterol esterification was lowest in the control group (9.8 ± 4.7 pmol/min.mg, P< 0.01) while the CR group presented a lower activity (37.28 ± 12.44 pmol/min·mg) compared with the HCHO group (55.89 ± 11.19 pmol/min·mg) (P < 0.01). ACAT activity was significantly correlated with total (r= 0.715, P < 0.01), FC (r= 0.597, P < 0.01) and CE (r= 0.479, P < 0.05) for all dietary groups suggesting a major role of this enzyme in hepatic cholesterol homeostasis. These results indicate that CHO restriction in the presence of high cholesterol favorably affects hepatic lipid metabolism by decreasing hepatic ACAT activity resulting in lower accumulation of cholesterol in the liver. The mechanisms underlying these effects are currently under investigation.