Obesity Causes of
Obesity
Obesity is a global problem in public
health and rates of obesity are increasing throughout the world (Fig. 46a). The
World Health Organization has defined obesity as ‘abnormal or excessive fat
accumulation in adipose tissue to the extent that health is impaired’. Obesity
is associated with an increased risk of Type 2 diabetes, hypertension,
hyperlipidaemia, cardiovascular disease, sleep apnoea syndrome and respiratory
failure, subfertility, arthritis and gallbladder disease. Targets are set using
the measurement of Body Mass Index (BMI; weight [kg] / height2 [m2])
(Table 46.1).
The relationship between BMI and
comorbidities (Fig. 46b) may vary between ethnic groups and certain studies use
different cut-off points for that reason. Special charts have been developed to
examine obesity rates in children. As central adiposity is associated with a
higher risk of metabolic disorders, the waist hip ratio or straightforward
waist measurement has been widely used to identify high-risk groups.
It has been estimated that about 315
million people world-wide fall into the WHO category of obesity. In wealthy
societies, all studies report a rate of about 20%, with more women falling into
the obesity category but a higher percentage of men found to be overweight (BMI
25–29.9). In the US, around 60% of the population has a BMI >25 kg/m2
and 27% are obese. Figures from Europe vary between countries and are slightly
lower than those seen in the US. In the world’s poorer countries there are wide
variations, particularly in developing economies. Thus in China the rates of
overweight and obesity are increasing, so that around 8–12% of the population
are defined as obese. In poor, rural African states obesity rates remain low
but recently they have increased dramatically in South Africa; a similar
picture related to affluence and urbanization can be seen in Central and South
America.
Obesity is the result of complex
interactions between genetic, environmental and psychological factors. Our
knowledge of some of the genetic factors that play a role in obesity, and the
endocrine and metabolic disturbances they induce, has increased dramatically.
However, it is clear that the current obesity epidemic has occurred too rapidly
for it to be accounted for by changes in the genetic pool. Environmental
factors are key to obesity, in particular the reduction in physical activity
associated with technological advances and the change to diets rich in
saturated fats and sugars.
Introduction
Obesity is becoming widespread in
modern human societies, particularly those in which large amounts of
carbohydrates and fats are consumed, and is not confined to affluent
populations, but also affects those (such as Mexico) in which relatively
inexpensive so-called fast foods are heavily marketed. Obesity is strongly
linked with several potentially life-threatening cardiovascular and metabolic
disorders, including thromboembolic disease and diabetes mellitus (see Chapter
41). A serious manifestation of the growing problem is the appearance of gross
obesity and Type 2 diabetes in young children.
Obesity may be defined as excessive
amounts of adipose tissue in relation to lean body mass. It may be quantified
as the body mass index (BMI; Table 46.1). Waist-to-hip ratio (WHR) is another
risk indicator and is the ratio of waist circumference to hip circumference. A
ratio of 1 or more indicates risk of heart disease and other obesity-related
problems. Generally, large fat deposits on the waist suggest higher risk due to
their correlation with insulin resistance than fat on thighs or hips. The cost
in health and economic terms is summarized in Table 46.2, compiled by the
National Audit Office.
Possible causes of obesity
Social influences. Dietary influences have been referred to above and
are doubtless significant causes of obesity. Social factors include the
extensive advertising of appetizing foods, drinks and of alcohol and the
intrusion of this advertising and of confectionary marketing into schools, a
phenomenon now commonplace. Additives such as monosodium glutamate, sucrose,
caffeine and a whole array of flavourings render these preparations capable of
inducing what is now increasingly referred to, even in the scientific
literature, as ‘binge eating’. Alcoholic high calorie beverages such as
‘alcopops’ are aggressively marketed. Furthermore, the stresses of a highly
competitive industrial society and of financial insecurity, coupled with
changing patterns of personal relationships, may have encouraged the phenomenon
of so-called ‘comfort eating’.
Evidence for genetic causes of obesity was initially provided by the
occurrence of familial obesity, and scientific evidence by the observation of
massive obesity in mutant ob/ob mice with a recessively inherited disease
(Fig. 46c). The mice eat voraciously and develop symptoms of Type 2 diabetes.
Apart from their hyperlipidaemia, hyperphagia, hyperglycaemia and insulin
resistance, the mice are also hypothermic and infertile. The ob gene was
cloned and its product expressed and termed leptin (Greek leptos,
which means thin). It is expressed only by fat cells. The role of leptin as an
endocrine hormone regulating body weight and energy metabolism through an
action in the brain is covered more fully in Chapter 45. The ob/ ob mice
possess two mutant copies of the ob gene that do not express leptin, and
administration of leptin to these mice reduces food intake, body weight,
increases sympathetic nervous activity and lowers circulating insulin levels.
The leptin receptor has been found mainly in the brain, although a short splice
variant has been found in several tissues in the periphery and in the choroid
plexus, where it may mediate the transfer of leptin into the brain.
Another obese mouse mutant, the db/db
mouse, was found to produce leptin but is unresponsive to it, because it
expresses a mutant leptin receptor causing leptin resistance. Leptin receptor
mutations have not been found to be causal in human obesity although other
target receptors, such as the MCR-4, are under intensive investigation.
Other endocrine hormones which through
inappropriate action might contribute to obesity are the adrenal
glucocorticoids, growth hormone, insulin, glucagon and thyroxine, all of which
play an important part in the regulation of glucose flows and therefore in the
integration of fat, carbohydrate and protein metabolism (see Chapter 44).
Autonomic malfunction has also been implicated in obesity in that
sympathetic innervation of thermogenic brown adipose tissue is impaired in
obese strains of mice, and parasympathetic activity appears to dominate.
Further evidence for autonomic involvement was the observation that removal of
pancreatic insulin-producing islets and transplantation under the kidney
capsule, which removes autonomic influences, reversed the hyperphagia produced
by lesions of the ventromedial hypothalamus in rats. In other words, high
circulating insulin suppressed the central feeding centres.
