33 / 52
VOLUME 13 NUMBER 2 • DECEMBER 2016
83
SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
Circulating apelin increases in obesity
56
and has been show to lower
glucose in normal and obese mice.
57
Homozygous apelin knockout
mice have severe heart failure in response to pressure overload
and diminished heart contractility in aged mice,
58
indicating a
role for the adipokine in maintaining cardiac function. Visfatin is
an adipokine that is predominantly expressed in visceral adipose
tissue and has been attributed to having insulin-like properties,
59
although this has since been disputed,
60,61
and recently visfatin has
been shown to have pro-inflammatory effects.
62
Vaspin is a serine
protease nhibitor and is reported to reduce expression of leptin,
resistin and TNF
α
and improves insulin sensitivity.
63,64
The recently discovered adipokine chemerin
65,66
increases
insulin sensitivity in 3T3-L1 adipocytes
67
and is essential for normal
adipocyte differentiation.
65,66,68
However, it has also been shown to
lower glucose tolerance in murine models of obesity/diabetes
69
and
to cause insulin resistance in human skeletal muscle cells, where it
was also observed to be pro-inflammatory.
70
Consequently adipose
tissue secretes both pro- and anti-inflammatory cytokines which
modulate metabolism by altering insulin resistance. Generally, pro-
inflammatory cytokine production increases and anti-inflammatory
expression decreases during insulin resistance and obesity.
Obesity and cardiovascular disease in Africa
Studies have shown that the prevalence of both cardiovascular
disease (CVD)
71
and obesity
7
is rising in Africa. Although it is not
certain that these two findings are linked, the observation that
CVD is more common in obese Africans
72
supports this premise.
This recent rise in the prevalence of obesity in Africa is attributed to
increased urbanisation and the associated ease of access to a more
westernised, calorie-dense diet.
73
Within Africa, the prevalence of CVD and its risk factors differs
across the various resident population groups. Accordingly, mortality
due to heart disease is higher in the Asian-Indian and European
ethnic groups of South Africa when compared to the indigenous
black African population.
74
Fasting serum cholesterol and triglyceride
levels are higher in Asian-Indian than African subjects,
75
with type
2 diabetes being more prevalent in the former population group.
76
The reasons for these ethnic differences in disease prevalence rates
and cardiovascular risk factors are not fully understood, although it
has been suggested that the higher abdominal fat mass observed
in Asian-Indian and European compared to African subjects may
be involved.
77
It is, however, of note that African subjects tend to be more
insulin resistant than Europeans
78,79
even though they have less
visceral adiposity. This would suggest either that visceral fat in
African compared to European subjects has a greater ability to
reduce insulin sensitivity, or that visceral adiposity is not involved in
determining the level of whole-body insulin sensitivity in the African
population. The latter hypothesis is unlikely since it has been shown
that waist circumference, independently of BMI, is a determinant of
insulin sensitivity in this population group.
80
It is also possible that
subcutaneous abdominal fat may play a more prominent role in
determining whole-body insulin sensitivity in African than European
females, as has been observed in a previous study.
79
Previous investigators have suggested that obesity in African
subjects is benign. This hypothesis was based on reports that
blood pressure, glucose and lipid levels were not elevated in obese
compared to lean African females.
81
However, this hypothesis
is challenged by data showing that there is a higher prevalence
of CVD in obese compared to non-obese African subjects.
72
Furthermore, it must be noted that these studies
81
did not take into
account body fat distribution, which is a major contributing factor
to the pathogenesis of obesity-related disorders. It is also of interest
to note that the African countries with the highest prevalence of
obesity have the highest prevalence of obesity-related disorders,
such as type 2 diabetes.
82
Adiposity and insulin resistance as a biological
advantage
Obesity has many negative connotations with regard to health.
It is associated with an increased risk of many diseases, ranging
from asthma to cancer. However, body fat does have an important
physiological role, including the maintenance of body temperature
and triglyceride storage. It also acts as an endocrine modulator of
insulin sensitivity and appetite. The negative effects of adiposity on
insulin sensitivity are often viewed as purely pathological. However,
insulin resistance has been proposed to have an important biological
role. It is now thought that insulin resistance is a normal physiological
response to obesity to slow down triglyceride deposition in
adipose tissue.
83
Studies have indeed shown that insulin resistance
may protect against weight gain.
84,85
Furthermore, the biological
adaptation of insulin resistance has been proposed as advantageous
in prehistory, during times of feast and famine. The ability to readily
store energy as fat would be beneficial until excessive adiposity
would limit the capability of our ancestors to hunt and escape
predation. Thus, insulin resistance would act to limit the rate of fat
deposition. It is therefore possible that insulin resistance evolved
to limit fat deposition in a period of human evolutionary history
when excessive caloric intake was not a common occurrence. In
modern times however, access to calorie-dense foods is not limited
and this homeostatic mechanism for limiting excessive weight gain
has been overpowered by new environmental conditions in which
famine has been replaced by feast.
Adipose tissue may play an important role in modulating
immunity. Adipocytes secrete a wide range of different cytokines
that have both pro- and anti-inflammatory properties. Also, lymph
nodes are normally found within adipose tissue depots and studies
have demonstrated a strong interrelationship between these two
tissue types. Therefore, the cells of the lymph node are supplied
with specialised free fatty acids by the perinodal adipocytes, and
dendritic cells from the lymph nodes are able to modulate lipolysis
of the surrounding adipose tissue.
86
Furthermore, the adipokine,
leptin has been shown to have effects on immune system
functionality. Subjects with a leptin gene mutation have very low
serum leptin levels and reduced numbers of CD4+ T cells and
low T-cell proliferation rates. All these defects are normalised by
administration of exogenous leptin.
87
Fat as a source of stem cells
Our perception of adiposity has recently changed again. In addition
to being an energy store, a major protagonist in the development
of insulin resistance and a modulator of satiety, adipose tissue has
been found to be an abundant store of stem cells. Adipose tissue
may therefore be seen more positively, given that these cells may be
used to treat a multitude of diseases.
Originally, Young
et al
.
88
isolated stem cells by digesting the
connective tissue in fat and cultured the liberated cells, which
they labelled the stromal vascular fraction (SVF). This was an