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.
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.