Cholesterol synthesis is increased and absorption decreased in non-alcoholic fatty liver disease independent of obesity.
OBJECTIVE
Non-alcoholic fatty liver disease (NAFLD) is associated with impaired glucose and lipoprotein metabolism. However, the metabolism of cholesterol in NAFLD remains unexplored. We investigated how fatty liver influences cholesterol metabolism in 242 non-diabetic subjects.


METHODS
Liver fat content was measured with proton magnetic resonance spectroscopy. Cholesterol metabolism was assayed with serum non-cholesterol sterols, surrogate markers of cholesterol synthesis and absorption. The analyses were performed with gas-liquid chromatography.


RESULTS
A total of 114 subjects had NAFLD and 128 subjects had normal liver fat content. Non-cholesterol sterols reflecting cholesterol synthesis (cholestenol, desmosterol, and lathosterol) were higher, and those reflecting cholesterol absorption (cholestanol and plant sterols) were lower in subjects with NAFLD than in controls, independent of body mass index. Liver fat content was positively associated with markers of cholesterol synthesis (r = from 0.262 to 0.344, p < 0.001 for all) and inversely associated with markers of cholesterol absorption (r = from -0.299 to -0.336, p < 0.001 for all). In the entire study group, synthesis and absorption markers were interrelated, indicating that the homeostasis of cholesterol metabolism was maintained. LDL cholesterol was similar in the two groups.


CONCLUSIONS
We demonstrated that although LDL cholesterol concentrations are unchanged, cholesterol metabolism in NAFLD is characterized by increased synthesis and diminished absorption of cholesterol. These changes are associated with liver fat content independent of body weight.
Simonen
Piia
P
Department of Medicine, Division of Internal Medicine, University of Helsinki, Helsinki, Finland. piia.simonen@hus.fi
Kotronen
Anna
A
Hallikainen
Maarit
M
Sevastianova
Ksenia
K
Makkonen
Janne
J
Hakkarainen
Antti
A
Lundbom
Nina
N
Miettinen
Tatu A
TA
Gylling
Helena
H
Yki-Järvinen
Hannele
H
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D002791:Cholesterol, Dietary / Q000493:pharmacokinetics*; D008078:Cholesterol, LDL / Q000378:metabolism; D005234:Fatty Liver / Q000150:complications / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000473:pathology; D012855:Sitosterols / Q000097:blood; D055815:Young Adult
D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL; D007328:Insulin; D012855:Sitosterols; C025473:gamma-sitosterol; C001521:lathosterol; D002784:Cholesterol