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.