The increase in Western-style food consumption in recent decades mirrors increases in obesity and insulin resistance seen in the populations of developed nations. The ‘eat-too-much, do-too-little’ theory of weight gain suggests that excessive calorie intake combined with a limited amount of physical activity causes a positive energy balance with results in weight gain. However, this ‘textbook’ myth that can be found perpetuated in most medical and nutritional academic texts is erroneous, and provably so from the peer reviewed literature. In fact, the epidemic of obesity is not caused by eating too much, but by eating the wrong foods. In particular, the properties of Western foods lead to metabolic dysfunction that triggers a detrimental cycle of weight gain and ill health. The high glycaemic index of fast food in combination with its very high fat content, induce hyperinsulinaemia and insulin resistance. Peripheral insulin resistance then increases the deposition of energy as fat and central insulin resistance causes metabolic dysfunction and abdominal obesity.
Of course it is easy to claim that Western style diets are to blame for the epidemic of obesity, but science requires a mechanisms to underlie the theory. Fortunately such a mechanisms exists and has been widely reported in the literature. The main problems with Western food can be summed up by saying that it is too low in fibre, contains carbohydrates that are too high on the glycaemic index, provides too much energy as fat, and is a source of fructose. In combination, these factors lead to metabolic changes in the consumer that affect the ability of the body to regulate energy metabolism and appetite. In addition, the components of the food that causes these problems could be defined as addictive, and this increases the likelihood that they will be consumed regularly, thus compounding their detrimental effects on metabolism. The metabolic changes induced by Western diets centre on the development of insulin resistance and insulin hypersecretion and an understanding of these changes is required to fully grasp the drivers of obesity.
Insulin resistance is likely caused, at least in part, by the accumulation of free fatty acids in skeletal muscle and hepatic tissue. This results in lipotoxicity, and these fatty acids are thought to interfere with the insulin signal cascade and thus inhibit the efficacy of function of insulin. The direct result of this insulin resistance in peripheral and central tissues is a hypersecretion of insulin. This is problematic because insulin is an anabolic storage hormone and the hyperinsulinaemia associated with insulin resistance feeds the growth and proliferation of fat tissue, leading to obesity, particularly that located centrally around the waist. This is because while hepatic and skeletal tissue can become resistant to insulin, adipose tissue tends to retain it sensitivity and thus high insulin levels encourage transport of circulating glucose into fat storage and away from skeletal muscle where oxidation could occur. Animal models suggest that hyperinsulinaemia increases expression of GLUT4 glucose transporters in adipose tissue, but down regulates them in muscle.
The neuroendocrine regulation of body weight occurs in a signal loop that is composed of an afferent signal from the visceral tissue to the paraventricular nucleus (PVN) of the hypothalamus and an efferent signal from the PVN of the hypothalamus to other parts of the hypothalamus, the limbic system and the visceral organs that regulate energy balance. Leptin, insulin and a number of gut peptides such as ghrelin and cholecystokinin are the primary signals that conveys information from the visceral tissue to the hypothalamus to inform the brain as to the nutrient and energy status of the body. In response to this signal, the hypothalamus secretes either anorexigenic peptides (e.g. α-melanocyte stimulating hormone and cocaine-amphetamine-regulated transcript (CART)), or orexigenic peptides (e.g. neuropeptide Y and agouti-related peptide), and these are integrated in the hypothalamus to produce an efferent signal. The major efferent pathways include sympathetic and parasympathetic pathways which promote energy expenditure or energy storage, respectively.
Insulin plays a role in the regulation of feeding, and its dysfunction in hyperinsulinaemia is pivotal in the development of obesity. Insulin is an afferent signal to the hypothalamus and the limbic systems where it regulates energy intake and the pleasure response from food, respectively. While insulin is an anabolic hormone and drives the accumulation of energy and fat in the periphery, in the central nervous system it tends to decrease energy intake. This negative feedback prevents the accumulation of excessive fat stores and elegantly allows the maintenance of a setpoint body weight. Insulin controls energy intake because it inhibits feeding behaviour and limits further energy intake, and because it reduces the pleasurable effects of foods. It has been hypothesised that when hyperinsulinaemia occurs in obesity, the hypothalamus becomes insulin resistant, and as a result the normal negative feedback that control eating behaviour breaks down, with a resultant hyperphagia and increased pleasure response from carbohydrate ingestion.
Another problem with hyperinsulinaemia is the fact that while both insulin and leptin bind to separate receptors they share inositol-3-kinase in their intracellular signal cascade. One downside of this might be the fact that hyperinsulinemia causes an increased expression of genes that inhibit the insulin receptor causing insulin insensitivity, but these genes also inactivate the leptin receptor and cause leptin resistance. The development of both leptin and insulin resistance in the hypothalamus is the lynchpin that drives obesity as the hypothalamus loses the afferent signals that inform it as to the energy status of the body. As a result, of a weak afferent signal, the hypothalamus interprets the conditions in the body as that of a starvation state. This results in the stimulation of appetite, a reduction in energy expenditure, and increased efficiency in the storage of ingested energy as fat. In combination with the increased pleasurable response to carbohydrate food induced by insulin resistance, this sets up the perfect storm for weight gain and ill health.
RdB
