From Cat
Lipid aqueous in the right eye of a Burmese kitten
Chylomicron metabolism
Chylomicron particles containing lipids are released from the intestine into the circulation. Cholesterol-rich chylomicron remnants form and are recognized by the apoprotein E receptor on hepatocytes. Once in the hepatocyte, cholesterol can be stored as cholesteryl ester (via the action of ACAT), can be excreted into bile as cholesterol or bile acids, or secreted into VLDL particles. Synthesis of cholesterol in the hepatocyte (via HMGCoA reductase) contributes to the available cholesterol pool. Lipoprotein lipase hydrolysis of triglyceride within secreted VLDL and exchange of apoproteins create a triglyceride-depleted IDL which forms the triglyceride-poor, cholesterol-enriched LDL particle. The LDL receptor recognizes apoproteins B and E and mediates uptake and removal of LDL from the circulation. A deficiency of lipoprotein lipase activity can result in decreased metabolism of VLDL to LDL and thus a prolonged appearance of VLDL in the circulation.

Hyperlipidemia is a lipid metabolism disorder of cats characterised by an increase in the plasma triglyceride (TG) and/or cholesterol concentrations. In cats, it has been shown for example that 25% of randomly selected Burmese cats in Australia exhibit marked post-prandial hypertriglyceridaemia after an oral fat tolerance challenge[1].

As chylomicrons and VLDL transport the majority of exogenous and endogenous TGs, respectively, hypertriglyceridemia results from an increase in one or both of these lipproteins in the circulation. Lipoprotein lipase (LPL) is involved in reducing the circulating TG concentration by hydrolysing TG from chylomicrons and VLDL to produce non-esterified fatty acids and glycerol[2]. This process is activated by teh co-factor apolipoprotein C2 (apoCII) and modulated by apolipoprotein E (apoE). Synthesis of LPL occurs mainly in adipose tissue, cardiac and skeletal muscle and it later attaches to the luminal surface of capillary endothelial cells via chains of heparin sulphate-proteoglycans[3]. Heparin administration is known to decrease LPL binding from these sites, resulting in an increased circulating LPL concentration which accelerates the rate of plasma TG clearance.

Over 60% of the variability in fasting serum lipid concentrations in humans is due to the effects of a variety of genes. Environmental factors such as dietary composition and obesity also influence fasting lipid concentrations. In humans, inherited primary disorders resulting in hypertriglyceridaemia include deficiencies in LPL, hepatic lipase and apoCII. Carying degrees of fasting hypertriglyceridaemia and/or hypercholesterolaemia are associated with these genetic disorders, although heterozygous carriers with a LPL deficiency may only show signs of disease when secondary factors such as obesity are present concurrently[4].


Primary lipid disorders are not commonly observed in cats. Lipid disorders secondary to hepatic lipidosis, diabetes mellitus, pancreatitis, hyperadrenocorticism and administraiton or corticosteroids or pregestagens are more likely to account for fasting lipaemia in this species. The best characterised primary lipid disorder in cats is inherited fasting hyperchylomicronaemia, an autosomal recessive disorder resulting from reduced LPL activity due to a point mutation in exon 8 of the LPL gene[5]. Cats homozygous for this condition develop severe fasting and post-prandial hypertriglyceridaemia, comprising a marked increase in chylomicrons and a mild to moderate increase in VLDL. Heterozygous cats have normal fasting TG concentrations but prolonged post-prandial lipaemia after an oral fat challenge. Persistently elevated lipid concentrations in homozygous cats result in the development of one or more of the following: lipaemia retinalis, peripheral neuropathy, cutaneous xanthomatosis and, less commonly, anaemia. Abdominal pain and pancreatitis have not been reported as features of hyperchylomicronaemia in these cats, in contrast to similarly affected canine or human patients. These clinical manifestations can be successfully managed by feeding a low fat diet (Kluger et al, 2009).

Another manifestation of lipid disorders in cats is lipid aqueous, a sporadic condition whereby lipid accumulates in the aqueous humour of the eye. This condition is thought to result from a transient breakdown in the blood-aqueos barrier, possibly due to primary anterior uveitis, in the setting of concurrently increased plasma chylomicron and/or VLDL concentrations. Large lipoproteins 'leak' across this barrier, causing a previously clear anterior chamber to become haze or even opaque (see figure). Lipid aqueous has been reported in Burmese cats. These patients initially present with one or more episodes of lipid aqueos, with or without concurrent uveitis, and mild to moderately elevated fasting TG referable to increased VLDL lipoproteins. Plasma TG levels are unchanged after intraveous administration of heparin. This condition has been described in Burmese and Tonkinese cats in Australia and the United Kingdom. In Australia and the UK, there is an over-representation of diabetic Burmese cats predisposing to this condition.

Secondary hyperlipidaemia has also been reported in Diabetes mellitus, Idiopathic hyperlipidemia, Pancreatitis, Nephrotic syndrome and Cholesterol ester storage disease.


Kittens with hyperchylomicronemia grow normally but have persistent lipaemia (excessive fatty substances in the blood resembling "cream of tomato" soup). Around 8-9 months they become unable to move their eyelids or chew properly. They cannot extend the toes and the lose the knee reflex, is lost. Multiple haematomas affect the peripheral nerves, causing loss of sensation. Some exhibited facial paralysis, limb paralysis/muscle atrophy and laryngeal paralysis resulting in breathing problems. Some symptoms are reduced after 2-3 months on a low fat diet, but prognosis is generally poor.

Diagnosis of hyperlipidemia is based on history, physical examination, examination of plasma and special laboratory tests. Concurrent illness is common, especially corneal lipid deposition, pancreatitis and diabetes mellitus.


Because of the clinical signs associated with primary hyperlipidemia, and the potential risks, hyperlipidemia should be treated aggressively in the cat. The underlying disorder in a secondary hyperlipidemia should be treated, but there is no specific therapeutic regimen for cats with inherited hyperchylomicronemia.

Fat Restricted-diet

The main therapy of primary hyperlipidemia involves feeding a low-fat diet with moderate protein content. Diets low in protein may cause an increase in serum cholesterol concentration and are therefore not recommended unless the presence of other conditions warrant their use. Human patients with inherited hyperchylomicronemia typically must restrict dietary fat intake to less than 15% of calories to control hyperlipidemia.

Feline diets with less than 10% fat (as-fed) or less than 30 g fat/1000 kcal are generally adequate. Protein content should be maintained at about 30% as-fed, or greater than 85 g protein/1000 kcal. A diet should not be chosen only on the percent fat present in the diet; the diet should be low in fat based on metabolizable energy (ME). Some diets appear low in fat on a percentage basis, but actually provide a higher fat content than expected when the amount of fiber in the diet and metabolizable energy are taken into account. For example, a diet containing 11% fat with an ME of 4000 kcal/kg provides only 27.5 g fat/1000 kcal, whereas a diet containing 9% fat with an ME of 3000 kcal/kg provides 30 g fat/1000 kcal. The presence of a blend of fructooligosaccharides and beet pulp in the diet may also be desirable, since this blend has been shown to decrease serum triglyceride and cholesterol concentrations in the dog.

Obesity in association with familial hyperchylomicronemia is uncommon, so it is usually not necessary to restrict caloric intake. If the cat is not obese, the amount of food offered may need to be increased because of the decreased calories provided by the new diet with decreased fat content. Many cats can continue to be fed free-choice. Treats should be restricted since these are most likely not low in fat content.

After feeding a low-fat diet for approximately 4 weeks, the presence of hyperlipidemia should be re-evaluated. Most cats will show at least partial resolution of hyperlipidemia with consumption of low-fat diets. Body condition should be assessed, and if there has been significant weight loss, the patient should receive an increased amount of diet, or possibly be switched to a different diet with higher caloric density.

If after 4 weeks hyperlipidemia is still present, the diet should be continued, and all other sources of food or treats removed. If there has been good owner compliance, then a switch to a different low-fat diet could be considered. The patient should then be reassessed after another one to two months. If hyperlipidemia still persists at that time, drug therapy could be added.

Omega-3 fatty Acid Supplementation

Fish oils are rich in omega-3 fatty acids, and have been the supplement of choice in the treatment of dogs with primary hyperlipidemias. However, little is known about the effectiveness of fish oil therapy in cats. Potential doses range from 10 to 200 mg/kg body weight. The fish oil supplement should contain a high percentage of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as these are long-chain omega-3 fatty acids. Products containing a high level of linolenic acid (also an omega- 3 fatty acid) will not be as effective, as cats have very low delta-6 desaturase necessary for the conversion of linolenic acid to longer chain omega-3 fatty acids.

The use of fish oil in the treatment of hyperlipidemia has been extensively studied in a number of other species. Fish oil supplement has resulted in a decrease in serum triglyceride and cholesterol in humans, rats, chicks, dogs, and rabbits[6].

Omega-3 fatty acids act to decrease the synthesis of triglyceride and VLDL in the liver[7], stimulate LPL activity, decrease the intestinal absorption of lipid, and increase cholesterol secretion into bile. Fish oil also decreases the serum concentration of free fatty acids, which may be important in the prevention of pancreatitis and diabetes mellitus.

Unfortunately there are no long-term studies to verify the safety and efficacy of any lipid-lowering agent in cats, and any therapy should be used with caution. One concern with fish oil therapy is the evidence that fish oil increases the concentration of lipoperoxides in LDL (Puiggros et al, 2002). The addition of vitamin E to the fish oil therapy regimen may enhance beneficial effects by increasing glutathione reductase activity and decreasing peroxide levels.

Other Therapeutic Agents

Other therapeutic agents have been used with variable results.

  • Gemfibrozil has been used to stimulate LPL activity and decrease VLDL secretion, and in cats is used at a dosage of 7.5 to 10 mg/kg body weight twice daily.
  • Niacin therapy has been used, however adverse effects have been noted.
  • Garlic extracts have been used to decrease cholesterol in humans, but have not been evaluated in cats.
  • HMGCoA reductase inhibitors reduce cholesterol synthesis and increase the excretion of LDL from the circulation, but their effectiveness in cats has not been studied.
  • Thyroxine therapy can decrease serum total cholesterol in humans, and is effective in lowering lipid concentrations in hypothyroid dogs, but its use has not been recommended for cats.
  • Gene therapy using a human adenovirus (AAV1-LPLS447X)[8]

The mutation characterizing the LPL deficiency present in humans and cats with hyperchylomicronemia has been identified, and gene transfer therapy has been attempted. Lipoprotein lipasedeficient cats were given an injection of an adenoviral vector containing the human LPL gene, with disappearance of triglyceride-rich lipoproteins up to day 14, at which time antibodies against the human LPL protein were detected. Concurrent administration of immunosuppressive therapy delayed antibody production, with resolution of hyperlipidemia for three weeks after administration. Gene replacement therapy for inherited hyperchylomicronemia may become a reality in the future.


  1. Kluger, EK et al (2010) Preliminary post-prandial studies of Burmese cats with elevated triglyceride concentrations and/or presumed lipid aqueous. JFMS 12:621-630
  2. Kluger EK et al (2009) Triglyceride response following an oral fat tolerance test in Burmese cats, other pedigree cats and domestic crossbred cats. JFMS 11:82-90
  3. Mead JR et al (2002) Lipoprotein lipase: structure, function, regulation, and role in disease. J Mol Med 80:753-769
  4. Miesenbock, G et al (1993) Heterozygous lipoprotein lipase deficiency due to a missense mutation as the cause of impaired triglyceride tolerance with multiple lipoprotein abnormalities. J Clin Invet 91:448-455
  5. Jones, BR et al (1986) Peripheral neuropathy in cats with inherited primary hyperchylomicronaemia. Vet Rec 119:268-272
  6. Schenck, PA (2009) Encyclopedia of Feline Clinical Nutrition Ed: Pibot P., Biourge V. and Elliott D.A. International Veterinary Information Service, Ithaca NY (www.ivis.org), Last updated: 11-Jun-2009; A5108.0609
  7. Rand, J (2006) Problem-based feline medicine. Saunders Elsevier, Sydney
  8. Ross, JD et al (2006) Correction of feline lipoprotein lipase deficiency with adeno-associated virus serotype 1-mediated gene transfer of the lipoprotein lipase S447X beneficial mutation. Human Gene Therapy 17(5):487-499