Adipose as a storage organ
The amount of adipose tissue varies hugely between individual horses and is affected by factors such as age, sex and breed (Wallis and Raffan, 2020). Estimation of body fat content by deuterium oxide dilution found adipose to account for 2.7-35.6% of total bodyweight in horses (Dugdale et al., 2012). There are two distinct types of adipose: white adipose tissue and brown adipose tissue. The white adipose tissue predominates and is specialised for energy storage. The brown adipose, named due to its colouration from the huge concentration of mitochondria, has a role in thermoregulation and, as a consequence, is abundant in new-borns and animals in hibernation (Kiranmayi and Bhargav, 2019). Most adult mammals have very low quantities of brown adipose and indeed, this form has not been described at all in the adult horse. There is great interest in brown adipose activation as a novel therapeutic target in human obesity (Liu et al., 2022); further research into brown adipose in the horse may therefore be of interest.
White adipose tissue is primarily an energy storage organ and is composed of adipocytes, in which lipid accumulates, as well as connective tissue, immune cells and blood vessels. Adipose can store almost 100 times more megajoules of energy than muscle and this resource allows mammals to cope with changes in energy availability over time. Humans with congenital lipoatrophy (Berardinelli-Seip syndrome), who have a functional failure of their adipose, rapidly develop severe insulin resistance and hepatic lipidosis, leading to liver failure and cardiovascular disease (Garg, 2004). This demonstrates that adipose an essential component of energy homeostasis and should not be viewed as always detrimental to health.
Adipocytes are formed from mesenchymal stem cells in a process called adipogenesis; a complex multistep process which includes the formation of pre-adipocytes from undifferentiated stem cells and the formation of mature adipocytes from these preadipocytes by accumulation of lipid. Equine adipose mesenchymal stem cells (MSCs) are well understood due to their regular use in the developments of treatments of musculoskeletal disorders (stem cell therapy) which has evolved due to their relative ease of acquisition and robust response to in vitro manipulation (Marycz et al., 2016). The in vitro characteristics of equine MSCs are very similar to those of humans, including the pre-adipocyte response to insulin and glucocorticoid stimulation which induces lipid accumulation and differentiation to mature adipocytes (Bukowska et al., 2021).
Adipocytes store fat as triglyceride (triacylglycerol) in one large lipid droplet per cell. Triglycerides from dietary fat are absorbed from the gut and transported to the adipose in the form of chylomicrons. Adipose, as well as liver, can also synthesise triglycerides from excess carbohydrates, a process known as de novo lipogenesis (DNL) (Ameer et al., 2014). The starting compound for DNL varies greatly between species, with horses using acetate, unlike humans who primarily use glucose or pigs who can use either (Suagee et al., 2010). Adipose tissue, as opposed to the liver, is the primary site of DNL in horses in contrast to humans (Suagee et al., 2010; Adolph et al., 2019), which may go some way to explain why fatty liver is less common in horses than other species. Aberrant DNL is associated with insulin resistance and cardiovascular risk in humans and is a potential link between excess carbohydrate intake and these conditions (Ameer et al., 2014), however very little is known about changes in DNL in equine disease.
In the face of increased calorie intake, adipose can expand by hyperplasia (increased adipocyte numbers derived from preadipocytes) or by hypertrophy (increase in individual cell size by lipid accumulation). The capacity for hyperplasia varies between adipose depots, as discussed later. When required, the stored triglycerides are broken down into glycerol and free fatty acids by lipolysis. These fatty acids are then available to mitochondria for respiration. The ability and speed at which adipose tissue breaks down stored triglycerides is one of the main distinguishing features between adipose depots.