Hyperlipidemia is the increased concentration of triglyceride (hypertriglyceridemia), cholesterol (hypercholesterolemia), or both in the blood.1-3 Hyperlipidemia in dogs and cats can be physiological (postprandial) or pathological. Pathological hyperlipidemia can result from increased lipoprotein synthesis or mobilization or decreased lipoprotein clearance.1 It can be primary (genetic or idiopathic) or secondary to other disease processes.1 Veterinarians should be familiar with how to recognize and manage this clinical disorder.
NORMAL LIPID METABOLISM
Lipids are large, heterogeneous, naturally occurring fatty and related compounds that are insoluble in water but soluble in ether and alcohol.4-6 Lipoproteins, which are lipid and protein complexes, are essential components of cell membranes and are critical in the stabilization and transport of lipids in plasma.4 Once in plasma, lipoproteins deliver lipids to appropriate tissues via specific cell receptors.4,7 That is, cell membrane receptors in different tissues bind to specific lipoproteins.
Lipoproteins are classified by size, density, electrophoresis, and apoprotein content.4 The four classes of lipoproteins are chylomicrons, very-low-density lipoproteins (VLDLs), low-density lipoproteins (LDLs), and high-density lipoproteins (HDLs) (Table 1).4,7 Triglycerides (glycerol and fatty acids) are transported as chylomicrons and VLDLs.4 Cholesterol is transported as LDLs and HDLs.4
Table 1: Major Lipoproteins and Characteristics*
Digestion and absorption
Lipid digestion is more complex than carbohydrate and protein digestion because fat must be solubilized in the water environment of gastric chyme to allow for enzymatic digestion.5 Lipid digestion requires pancreatic lipase, pancreatic colipase, and bile from the gallbladder.5
Once in the duodenum, lipid is solubilized, with the assistance of gastric peristalsis, in bile and gastric chyme into lipid droplets.8 Pancreatic colipase then binds to these lipid droplets and anchors pancreatic lipase.5,8 Pancreatic lipase is then activated and degrades triglycerides to monoglycerides and free fatty acids and hydrolyzes dietary cholesterol.8 The monoglycerides, cholesterol, and free fatty acids along with bile acids form mixed micelles, with the more polar substances on the surface and the more hydrophobic substances (fat-soluble vitamins A, D, E, and K) in the core.5,8 The micelles diffuse passively into the enterocytes.5,8
Once absorbed by enterocytes, fatty acids and glycerol are repackaged into triglycerides and are bound to apolipoprotein to form chylomicrons.5,7,8 The absorbed cholesterol is also incorporated into the chylomicrons.8 Chylomicrons transport fat in the aqueous environment of lymph and plasma. They originate exclusively from the diet and are present in the plasma 30 minutes to two hours after a fat-containing meal is consumed.3 Lipoprotein lipase, which is present in high concentrations near the endothelial cells of muscle and adipose tissue, is activated and hydrolyzes the triglyceride of chylomicrons to fatty acids and glycerol within six to 10 hours.3,4,7 The activity of lipoprotein lipase is enhanced by heparin, insulin, and thyroid hormone.3,9 The free fatty acids diffuse into cells and are either resynthesized to triglycerides and stored in adipocytes or used for energy in myocytes and other cells.7 The remnants of the chylomicrons remain in the plasma and are removed by the liver.3,4,7