30 Hyperlipemia

Hyperlipemia is a life-threatening medical condition seen almost exclusively in pony, donkey and miniature horse breeds. It results from sudden and severe breakdown of body fat stores and nutrition plays a key role in the pathogenesis and treatment of the condition. Intensive therapeutic intervention is an important component in achieving a successful outcome although an overall survival rate of only 56% is reported in six case series published since 1992 (Durham 2006, Hallebeek & Beynen 2001, Mogg & Palmer 1995, Rush-Moore et al 1994, Waitt & Cebra 2009, Watson et al 1992b).

Epidemiology and risk factors

Risk factors for hyperlipemia may be considered in two categories: pre-existing inherent factors that predispose an individual to hyperlipemia; and then precipitating factors that trigger hyperlipemia in predisposed individuals (Table 30-1).

Predisposing factors

Predisposition to hyperlipemia is largely related to insulin resistance (IR) and increased nutritional requirements. Pony, donkey and miniature horse breeds demonstrate a relative insensitivity to insulin that may be further compounded by obesity and a sedentary lifestyle (Jeffcott et al 1986, Reid & Mohammed 1996). IR facilitates mobilization of fat and glycogen stores whenever caloric intake is insufficient (Jeffcott et al 1986, June et al 1992) and thus represents an inherent prolipolytic status that predisposes to hyperlipemia (Breidenbach et al 1999). Mature animals appear predisposed to hyperlipemia (Jeffcott & Field 1985, Reid and Mohammed 1996) perhaps as a result of decreasing insulin sensitivity (Murphy et al 1997) although cases are occasionally encountered in foals and even neonates (Gilbert 1986, Hughes et al 2002, Tan et al 2005). Pregnancy is also associated with IR (Fowden et al 1984) and, moreover, increased nutrient demands that further promote fat mobilization. The latter is also the likely explanation for increased hyperlipemia risk associated with lactation.

Females appear predisposed to hyperlipemia largely due to pregnancy or lactation, although one study found female donkeys to be at twice the risk of males even when not pregnant or lactating (Reid & Mohammed 1996). Examination of data from 135 published cases of hyperlipemia shows 1.5 times as many reproductively inactive females compared with males also supporting that being female is a risk factor independently from pregnancy and lactation (Fig. 30.1). Further unpublished data reveals a significantly higher serum insulin concentration in female than male donkeys supporting IR as a factor in this gender predisposition (N. du Toit, personal communication).


Processes controlling fat mobilization

The delivery of fatty acids (FAs) from stored triacylglycerols (TGs) in adipose tissue for oxidation by other cells represents the major energy supply route through the body, especially at times of negative energy balance. This mobilization is achieved by three intercoordinated processes (Fig. 30.2):

These three processes are described in further detail below.

Adipose lipolysis

Regulation (Table 30-2a)

ATGL and HSL represent the key, rate-limiting steps in adipose TG hydrolysis and are both closely controlled by the endocrine system. Both ATGL and HSL lipolytic activity is stimulated by catecholamines (beta adrenoreceptors) and inhibited by insulin (Large & Arner 1998). Additional regulatory factors are listed in Table 30-2a (Coppack et al 1994, Large & Arner 1998, Zechner et al 2009). Insulin may further limit FA release from adipose stores by promoting re-esterification of free FAs and glycerol into TG. Regulation of the two enzymes differs slightly in that HSL activity increases during prolonged fasting whereas ATGL is acutely up-regulated following feed withdrawal, probably in response to increased glucocorticoid levels (Villena et al 2004, Zechner et al 2009). Tumor necrosis factor-α (TNF-α) is a potent stimulator of lipolysis during sepsis probably via stimulation of ATGL (Zechner et al 2009).

Extraction of FAs from plasma VLDL-TG

Pathophysiology of hyperlipemia

Hyperlipemia inevitably follows when adipose lipolysis (ATGL- and HSL-dependent) and consequent hepatic VLDL synthesis (MTP- and substrate-dependent) exceeds the rate of clearance of plasma VLDL (LPL- and VLDL receptor-dependent). Risk factors for hyperlipemia (Table 30-1) are likely to be associated with conditions including IR, negative energy balance, increased sympathetic and adrenocortical activity and systemic inflammation. Under such conditions it would be expected that adipose lipolysis and hepatic VLDL synthesis would be increased (Table 30-2a,b, Fig. 30.2). Anorexia increases VLDL clearance by muscle (but not fat), although this process could be antagonized by inflammatory cytokines (Fig. 30.2, Table 30-2c). In a study of hyperlipemic ponies, Watson et al (1992a) found increases in the rates of all three key processes: adipose lipolysis, hepatic VLDL synthesis, and VLDL clearance. However, the majority of the cases studied were primary hyperlipemia and it is possible that effects on VLDL clearance could be different in hyperlipemia secondary to inflammatory diseases due to the inhibitory effects of cytokines (TNF-α and GM-CSF) on LPL and the VLDL receptor (Table 30-2c).

In addition to excessive plasma lipid, tissues may also become saturated with fatty infiltration. Amongst these, the liver appears especially prone to lipidosis. As described above, the liver is a key conduit and site for lipid metabolism, extracting and processing adipose tissue-derived free fatty acids and glycerol from the hepatic arterial supply (during fasting) as well as lipid-rich chylomicrons from the hepatic portal venous supply following absorption and synthesis by the intestine (postprandially). The liver’s capacity for extraction and synthesis of lipid may outweigh the rate of VLDL secretion leading to hepatic lipidosis and progressive impairment of liver functions.

Jun 8, 2016 | Posted by in EQUINE MEDICINE | Comments Off on Hyperlipemia
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