Hyperlipidemia is defined as an increased blood concentration of triglyceride (hypertriglyceridemia) and/or cholesterol (hypercholesterolemia). This condition in dogs and cats can be physiological (e.g. postprandial) or pathological. Pathological causes include increased lipoprotein synthesis or lipid mobilization, or decreased lipoprotein clearance. It can be primary (genetic or idiopathic) or secondary to other disease processes such as hypothyroidism, pancreatitis, hyperadrenocorticism, or diabetes mellitus.

There are four classes of lipoproteins, namely, chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). Whereas, triglycerides (glycerol and fatty acids) are transported as chylomicrons and VLDL, cholesterol is transported as LDL and HDL.

Dietary fat is emulsified into micelles by the action of bile acids and gastric peristalsis. Lipid digestion is more complex than that of carbohydrates and proteins, and requires pancreatic lipase, pancreatic co-lipase, and bile from the gallbladder.

In the duodenum, lipid is solubilized into lipid droplets, with the assistance of gastric peristalsis. Pancreatic co-lipase then binds to them and anchors pancreatic lipase. Pancreatic lipase becomes activated and degrades triglycerides to monoglycerides and free fatty acids, and hydrolyzes dietary cholesterol. These components collectively form mixed lipid micelles, which diffuse passively into the enterocytes.

Fatty acids and glycerol in the enterocytes along with cholesterol are then repackaged into triglycerides and are bound to apolipoprotein to form chylomicrons. Chylomicrons transport fat from the diet and are found in the plasma within 1/2–2 hrs after consuming a fat-containing meal. Lipoprotein lipase is activated and hydrolyzes the triglyceride of chylomicrons into fatty acids and glycerol within 6 -10 hrs. The activity of lipoprotein lipase is enhanced by heparin, insulin, and thyroid hormone. Free fatty acids diffuse into cells and are either stored as triglycerides in adipocytes or used for energy in myocytes and other cells. Any remaining plasma chylomicrons are removed by the liver.

After removal by the liver, chylomicrons are re-synthesized into triglycerides, and packaged into VLDL particles. Activated intracellular hormone-sensitive lipase is then stimulated by epinephrine, nor-epinephrine, ACTH, corticosteroids, growth hormone, and thyroid hormone. VLDL are important triglyceride transporters during fasting. As VLDL lose fatty acids, their density increases and VLDL become LDL.

Low-density lipoprotein is VLDL minus triglyceride. Rich in cholesterol and phospholipids, the major function of LDL is to transport cholesterol—an important component of cell membranes and hormone synthesis—to tissues. Excess LDL bind to LDL receptors on hepatocytes and are removed from plasma.

High density lipoprotein is synthesized and secreted from both the liver and intestine. It comprises most of the cholesterol in dogs and cats; and serves as a reverse cholesterol transporter by scavenging excess cholesterol from cells, and returning it to the liver for excretion into the bile.

• Dietary postprandial hyperchylomicronemia
  
• Increased VLDL production starvation, nephritic syndrome, hyperadrenocorticism, diabetes mellitus, pancreatitis
  
• Ineffective VLDL clearance diabetes mellitus, hypothyroidism, pancreatitis, hepatic cholestasis, hyperchylomicronemia in cats
  
• Idiopathic hyperlipoproteinemia of miniature schnauzers, other breeds

In dogs, hyperlipidemia is manifested clinically by dysfunction in the gastrointestinal, neurologic, and ocular systems. Primary clinical findings include: vomiting, diarrhea, abdominal pain, abdominal distention, anorexia, seizure activity, and lipemia of the retina and aqueous humor. While clinical signs and history may be consistent with pancreatitis, laboratory data and imaging studies may fail to support this diagnosis. Very high chylomicronemia (> 1,000 mg/dL) can result in the occlusion of organ blood vessels. If the pancreatic vessels are occluded, the subsequent tissue damage causes secondary pancreatitis. Thus, patients that present with pancreatitis should be evaluated for hyperlipidemia.

In cats, hyperlipidemia has been reported to cause cutaneous lesions and peripheral neuropathies. The most common clinical finding is cutaneous xanthoma, a painless raised lesion containing lipid-laden macrophages or foam cells. Although sites of nerve involvement vary, Horner's syndrome, and tibial and radial nerve paralysis are most common.

While dogs and cats, unlike people, are considered resistant to the atherosclerosis associated with hypercholesterolemia, at cholesterol concentration above 750 mg/dL in dogs and 650 mg/dL in cats, a relative increase in the LDL particles occurs that predisposes them to atherosclerosis. Hypothyroidism is the disease most commonly associated with atherosclerosis in dogs.

Hyperlipidemia should be considered in dogs and cats that present with compatible clinical signs or with significant fasting lipemia. In addition to the appearance of the serum or plasma, more helpful diagnostic tests include: measuring triglyceride and cholesterol concentrations in samples from fasting patients; tests to rule out underlying diseases (e.g. low-dose dexamethasone suppression test, serum thyroid hormone concentrations, serum pancreatic lipase immunoreactivity).

Lipemia Effects on Serum Chemistry Parameters
Lipemia may affect accurate measurement of certain serum chemistry analytes. If lipemia is present in a particular sample, the potential effects are listed at the bottom of Antech's serum chemistry reports.

Treatment of secondary hyperlipidemia involves treating the underlying disease. Primary hyperlipidemia may require feeding a low-fat diet or administering lipid-lowering agents such as omega-3 fatty acids, niacin, gemfibrozil, lovastatin, or cholestyramine.

Dietary modification. In some patients, switching the patient to a low-fat diet may be the only therapy needed. Diets should contain less than 20% fat on a metabolic energy basis for dogs and less than 25% for cats. Treats should be restricted to 5% of the daily caloric intake and changed to low-fat varieties (slivers of carrots or celery or brown rice crackers).

Reference: Excerpted from Thomason, Flatland, and Calvert, Vet Med 9:588-598, 2007.