The Relationship between Obesity and Insulin Resistance

Metabolism – the sum of all the chemical reactions in the body necessary for sustaining life - and immunity – the ability of the organism to defend against threats posed by the invasion of microorganisms such as bacteria and viruses – are intimately linked in the biology of mammals. It is this relationship that allows the organism to adapt to changes in both the internal and external environments. However, within the modern western diet and lifestyle that promotes the development of obesity, this close association of metabolism and immunity can have deleterious consequences. Through the evolutionary history of the human species, humanity has had to survive in the face of the possibility of death as a result of starvation, infection and predation. It is only relatively recently in human societal development that such threats have been significantly lessened due to the introduction of agriculture to meet the nutritional needs of human populations and significant progress in technology and medicine. These age-old threats have been supplanted, however, by new concerns regarding individual mortality posed by cardiovascular disease, diabetes and cancer. The evidence now strongly indicates that obesity is an essential component of these troubling diseases. Between 1980 and 2008, the total number of obese individuals has essentially doubled worldwide to .5 billion individuals and the global death rate attributed to obesity is currently at ~ 3 million people per year. Drs. Justin Odegaard and Ajay Chawla from the Cardiovascular Research Institute at the University of California at San Francisco have examined the “cellular and molecular connections between chronic low-grade inflammation, insulin resistance and obesity-induced metabolic disease.” The focus for this report will be on the relationship between obesity and insulin resistance. Within this context, obesity can be defined as an imbalance between caloric intake and energy expenditure – calories in/calories out. This state of imbalance leads to the storage of excess nutrients in white adipose tissue (WAT). For lean individuals this imbalance is readily compensated by metabolic adjustments in WAT, liver and skeletal muscles. However, in a state of chronic over-nutrition, these pathways are overwhelmed leading to wide-ranging intracellular and extracellular dysfunction. Although these deleterious effects are the result of complex metabolic processes, the end product of these disturbances leads to the inhibition of insulin signaling – insulin resistance - through the modification of the insulin receptor substrate resulting in diabetes. In addition, the metabolic stress responses that are a product of chronic obesity, leads to the triggering of the innate immune receptors resulting in inflammation. This is, indeed, troubling data especially in regards to global public health. It appears that chronic over-nutrition is a cause for concern since the health ramifications that result from obesity have a major impact on individual quality of life and mortality.