Obesity and Dyslipidemia. AR Esteghamati, MD Associate Professor of Internal Medicine Endocrinology and Metabolism Research Center Tehran University of Medical Sciences. Objectives. prevalence of obesity Hyperlipidemia as a CVD Risk factors Normal lipid metabolism
AR Esteghamati, MD
Associate Professor of Internal Medicine
Endocrinology and Metabolism Research Center
Tehran University of Medical Sciences
The dyslipidemic phenotype, associated with obesity, is characterized by
Each 1-mmol/L (89-mg/dL) TG increase was associated with :
A family of proteins that occupies the surface of the lipoproteins; play crucial roles in the regulation of lipid transport and lipoprotein metabolism.
Chylomicrons transport the TGs to target tissues
hydrolyzed by the enzyme LPL located on the endothelial surface.
Upon hydrolysis of TGs, nonesterified fatty acids (NEFA) are formed
taken up by adipose tissue for storage or by skeletal muscle for use as an energy source.
Body relies on fatty acids as an energy source
Glucagon signals the breakdown of TGs by hormone-sensitive lipase (HSL) to release NEFA.
If the liver is taking up more fatty acids than it can use in the VLDL formation and excretion
these surplus fatty acids will be stored in the liver in the form of fat droplets.
Reduced efficiency of insulin:
leads to hyperglycemia and a compensatory hyperinsulinemia.
stimulating DNL in the liver through activation of the previously described SREBP-1 pathway.
contribute to lower HDL-c levels
LCAT mediates the transfer of linoleate from lecithin to free cholesterol on the surface of HDL to form cholesteryl esters that are then transferred to VLDL and eventually LDL.
Excess free cholesterol in tissues
Apo AI is a cofactor for esterification of free cholesterol by LCAT.
Deficiency of LCAT can be caused by mutations in the enzyme or in Apo A1. LCAT deficiency causes low levels of cholesteryl esters and HDL
Pre-HDL HDL3 HDL2 HDL1(HDL-E)
Increased CETP Contributes to
1- Decreased HDL-c
through facilitating transfer of cholesteryl esters from HDL to TG-rich lipoproteins (chylomicrons, VLDL)
This cholesteryl ester transfer :
2- creates a TG-rich HDL
serves as a better substrate for clearance by hepatic lipase
induction of cholesteryl ester exchange in LDL takes place for TGs in VLDL.