Inflammation in Obesity is Common Link Between Defects of Fatty Acid Metabolism and Insulin Resistance

In this article, Diabetes Type II induced inflammation is more closely examined for the particular pathway regarding Tumor Necrosis Factor alpha (TNFa), although it is important to remember that the relationship between Type II Diabetes and obesity is multi-faceted and not limited to one specific pathway (which makes it so difficult to understand). The basis of this particular pathway proceeds sort of like this: The excess caloric intake and reduced caloric expenditure of modern lifestyle has lead to an increasing rise in obesity, which is due to the rise in fatty acids in the body and thus an increase in adipocytes in which to store the fat. Unfortunately, adipocytes have proven to not be pure storage centers, but have in fact been shown to have significant endocrine and paracrine interaction with surrounding cells, including macrophages. By increasing the number of adipocytes in the body, an increase of macrophages will be recruited to the area and an increase in TNFa production will occur. This article describes how TNFa has been shown to have a variety of implications, including: inflammation (an important role of macrophages), decreased insulin-stimulated glucose disposal, increased insulin resistance, and an increase in protein phosphatase 2C (PP2C). PP2C inhibits another cytokine called AMP-activated phosphokinase (AMPK), which is responsible for helping to maintain proper metabolic balance. These effects all contribute to a decreased level of skeletal muscle fatty acid oxidation, which simply leads to an increase in fatty acid production and repeats the cycle.

Questions: 1)Why do you think macrophages (responsible for TNFa) would be recruited to the area of adipocytes in fat tissue to begin with? 2) Is this recruitment preventable? 3) How much of a real contribution does TNFa have in inducing the inflammatory response in obesity/type II diabetes?