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March 07-08, 2019 | London, UK
Journal of Diabetology | Volume 3
Annual Summit on
Diabetes, Obesity & Heart
Diabetes, Endocrinology and Metabolic Syndrome
International Conference on
Joint Event
&
Dyslipidemia alters HDL metabolism and function in NAFLD
T Kasumov, A McCullough and S Dasarathy
Cleveland Clinic, USA
D
yslipidemia and inflammation play key roles in the
pathogenesis of both nonalcoholic fatty liver disease
(NAFLD) and atherosclerosis. NAFLD, particularly its severe
form non-alcoholic steatohepatitis (NASH) is associated with
increased cardiovascular disease (CVD) risk. HDL (a CVD risk)
are decreased in NAFLD but whether HDL function is abnormal
in NAFLD is unknown. The aim of this study was to investigate
HDL function and to examine the effect of dyslipidemia and
inflammation on HDL metabolism in patients with biopsy
proven simple steatosis (SS) and NASH. H
2
O-metabolic labeling
was used to study HDL function and HDL protein dynamics in SS,
NASH patients (8/group) and matched healthy controls (n=9)
in vivo. To assess the role of HDL maturation and remodeling
on stability of HDL proteins, we quantified the activities of
cholesterol ester transfer protein (CETP), the key HDL protein
involved inHDL lipidation. HDL’s anti-oxidant, anti-inflammatory
and cholesterol efflux properties were measured using in
vitro assays. Compared to controls, SS and NASH subjects had
significantly higher levels of plasma triglyceride, insulin, and
weremore insulin resistant (HOMA, P<0.05) with no differences
in total cholesterol, HDL cholesterol (HDLc), ApoB100 and
ApoAI levels. NAFLD patients had increased production and
degradation rates of both HDLc and ApoAI that kept their levels
stable. The degradation rates also were increased of other
HDL proteins. NAFLD patients had increased activities of CETP,
indicating altered HDL lipidation. NAFLD induced alterations in
HDL metabolism were associated with reduced anti-oxidant
but increased pro-inflammatory activity of HDL (P<0.05)).
However, no differences were observed in either HDL function
or the kinetics of HDLc and HDL proteins between SS and NASH
subjects. HDL turnover and function are altered in NAFLD
without any differences between SS and NASH, indicating that
dyslipidemia is more important than hepatic inflammation on
altered HDL metabolism and functions in NAFLD.
e:
tkasumov@neomed.edu