CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 3, May/June 2011
148
AFRICA
2003–2004.
6
A meta-analysis of studies measuring prevalence of
obesity in west African countries showed that the prevalence of
obesity in urban areas rose from 7.0% in 1990–1994 to 15.0%
by 2000–2004.
7
Data from China demonstrated that the preva-
lence of overweight and obesity was 14.6% in 1992 and 21.8%
in 2002.
8
Similar trends have been reported around the world.
The increasing prevalence of obesity in the developing world is
compounded by the cultural view of obesity as being a positive
attribute, signifying both health and wealth. This is particularly
so in African nations,
9
and is in stark contrast to the Western
ideal, as portrayed in the mass media, of thin is beautiful!
Central adiposity, ectopic fat deposition and
obesity-related co-morbidities
‘Not all fat is created equal’ may be the new dogma in obesity
research, with many studies reporting that the pathological effects
of excessive adiposity are dependent not only on the quantity of
fat, but on the distribution of the fat mass. The adipose tissue
surrounding the major abdominal organs, the visceral fat, is
thought to be the principal adipose depot involved in the aetiol-
ogy of obesity-related disorders, with the subcutaneous fat depot
playing a less prominent role.
10
Closer scrutiny of adipocytes
isolated from these two fat depots has corroborated this view
and shown fundamental metabolic differences as well as a higher
production from visceral adipocytes of adipose tissue-derived
cytokines (adipokines), which may play an important role in the
aetiology of many obesity-related diseases.
11
It has been proposed that the rate of lipid uptake is greater in
the subcutaneous than the visceral adipose tissue depot until the
former site approaches its limit for lipid storage, when triglycer-
ide uptake into the visceral depot predominates.
12,13
Lipid accu-
mulation in obesity promotes both adipocyte hyperplasia and
hypertrophy,
14,15
with storage mainly occurring in pre-existing
adipocytes. As hypertrophy progresses, the storage capacity of
the cells in subcutaneous adipose tissue becomes limiting and
lipids that are not readily accumulated are shunted to the visceral
stores. Excessive fat accumulation in the visceral stores leads to
the secretion of free fatty acids into the portal vein, which, with
the secretion of pro-inflammatory adipokines, leads to hepatic
insulin resistance and aberrant accumulation of lipids in hepato-
cytes and the resultant hepatic steatosis.
16
In obese individuals, the inadequate lipid storage capacity of
the body’s adipose tissue depots leads to ectopic fat deposition
not only in the liver but in other organs such as skeletal muscle
and the insulin secreting
b
-cells of the pancreas. It has been
suggested that this ectopic fat deposition may play an important
role in the aetiology of both insulin resistance and
b
-cell failure.
17
Furthermore, in obesity, increased fat deposition has also been
noted peri-vascularly and peri-cardially and within myocytes.
18
It
has been suggested that this may contribute to vascular stiffness,
cardiac dysfunction, hypertension, atherosclerosis and sodium
retention, which are all characteristics of the cardiovascular
disease observed in obese subjects.
18
Adipose tissue, a paracrine and endocrine
organ
Adipose tissue is no longer just seen as a fat store, but is consid-
ered a true secretory tissue, with differences in secretion under-
pinning the greater pathogenicity of visceral than subcutaneous
fat masses. Adipocytes are known to secrete pro-inflammatory
cytokines such as TNF
α
and IL-6, which in conjunction with
elevated free fatty acids (FFAs), promote insulin resistance.
11
These cytokines are elevated in obesity and have been proposed
to act in an autocrine loop, inhibiting the adipocyte hyperplastic
response, which in turn leads to hypertrophy and further secre-
tion of FFAs and pro-inflammatory cytokines.
Adipocytes produce a multitude of secreted peptides other
than pro-inflammatory cytokines that have been linked to some
of the obesity-related co-morbidities. Many of these molecules,
such as plasminogen activation inhibitor 1 (PAI-1), angiotensino-
gen (AGT), monocyte chemo-attractant protein 1 (MCP-1) and
resistin, have effects on vascular function. Plasminogen activa-
tion inhibitor 1 inhibits plasminogen activation and leads to
fibrinolysis and a pro-thrombotic state.
19,20
PAI-1 is secreted more
by visceral than subcutaneous fat
21
and is also a risk factor for
coronary artery disease (CAD),
22
whereas angiotensinogen has
been implicated in the aetiology of hypertension and is upregu-
lated in obesity,
23,24
with production being higher in visceral fat.
25
Furthermore, angiotensinogen is the precursor of angiotensin II
of the vasoconstriction renin–angiotensin system and may be a
causal agent for the hypertension seen during obesity.
26
Monocyte chemo-attractant protein 1 is also secreted predom-
inantly from the visceral depot, is overproduced during obesity
and participates in the recruitment of macrophages and mono-
cytes into the arterial cell wall. As this recruitment may lead to
atherosclerosis, MCP-1 was measured in patients with or without
CAD, and it was found to be elevated in the former group.
27
Adipocytes also secrete resistin, which stimulates inflammatory
cytokine production, as well as decreasing endothelial cell adhe-
sion molecule (iCAM-1, vCAM-1, Ccl-2) production, which
may promote atherosclerosis.
28
The role of resistin in insulin
resistance is still unclear.
29,30
Adipose tissue also secretes other peptides that have effects
peripherally and centrally. The most investigated of these is
leptin, a satiety factor which was first characterised in a rodent
model of monogenic obesity, the ob/ob mouse.
31
Since the isola-
tion and characterisation of leptin (from the Greek leptos: thin),
adipose tissue has been viewed as a true endocrine organ. Leptin
is secreted by adipocytes and modulates food intake by suppress-
ing orexigenic peptides (Agouti-related peptide and neuropep-
tide Y) and upregulates anorexigenic peptides (corticotropin-
releasing hormone and
a
-melanocyte stimulating hormone) in
the brain.
32
It also stimulates fatty acid oxidation and prevents
lipid accumulation in adipose tissue.
33,34
This forms a negative
feedback mechanism, where increased fat mass produces more
leptin, which reduces food intake, inhibiting further adipose
expansion and limiting leptin expression. It was initially thought
that this feedback loop could be used to inhibit food intake in the
obese, but clinical trials of leptin analogues had little success,
because endogenous leptin has since been found to be elevated
in the obese, who often exhibit leptin resistance.
35
The adipokine
has since been attributed to being a signal for energy deficiency,
rather than a signal to lose weight, as excessive weight loss will
result in decreased leptin levels and a consequential increase in
food intake.
36,37
Since the characterisation of leptin, many other adipokines
have been discovered, such as apelin, visfatin, chemerin
and vaspin, with adiponectin being the most fully studied.
