The toxicity of obesity can be divided into three camps: physical, hormonal and inflammatory.  The physical camp is fairly straightforward, the more you weigh, the harder it is on the musculoskeletal system to carry that weight.  Weight in the knees for example is multiplied by a factor of five so every extra 20 pounds of weight causes an extra 100 pounds of force on the knee joint.  

The hormonal toxicity of obesity is related to insulin resistance.  Leptin acts on the fat to increase the levels of another hormone called adiponectin.  Adiponectin is needed to make new fat cells.  In obesity however, with leptin resistance, adiponectin levels are low.  As a result the fat cells get overstuffed with fat.  The more they are stuffed, the more leptin they produce, feeding the cycle of leptin resistance.  Eventually fat needs to be stored elsewhere and the two spots the body chooses are muscle and the liver.  When fat is stored in the liver and in the muscle it decreases the ability of those cells to respond to insulin.  This forces the pancreas to make more insulin to try and get the liver and muscle cells to respond appropriately and keep the blood sugar under control.  A simple way to think about this is that it is the fat that causes insulin resistance and not the sugar.

The final toxicity of obesity is through increased inflammation.  Leptin stimulates an immune cell called a monocyte.  In response the monocyte releases several chemicals: TNF alpha (tumor necrosis factor), IL-6 (interleukin 6) and IL-12 (interleukin 12).  The IL-6 also stimulates the production of CRP (C reactive protein).  All of these serve to turn up the volume of the immune system and cause damage.

To see how each of these camps of toxicity contribute to disease see the sections below on a variety of obesity related conditions.