The recent acticle, "Inflammation in Obesity-related Diseases," (1) is an excellent article but must be broken into components in order to truly appreciate the wealth of information it has to offer. Here I will provide only a brief review of the pro and anti inflammatory adipokines that may, in the future, be targeted by pharmacology. Linking obesity and the roles of adipocytes and lymphocytes (the non-adipocyte cell fraction of adipose tissue) to the production of adipocytokines, the article identifies those which are upregulated (and induce insulin resistance and other inflammation-related diseases) and those which are downregulated. The article is best summed up by this quote, "The reciprocal regulation of pro and anti inflammatory adipocytokines is an important feature of adipose tissue-based inflammation."
Amongst the upregulated pro inflammatories are leptin, TNF alpha, IL6, resistin, and MCP1, while the downregulated anti inflammatories include adiponectin, IL-1RA, IL-10. Leptin upregulates lymphocyte development, cytokine expression, proliferation and apoptosis, and in the company of other pro inflammatory adipocytokines, trigger JNK-1 and IKK beta to effect changes in inflammation and glucose homeostasis. Both JNK-1 and IKK beta have been known to be associated with atherosclerosis and steatohepatitis as well. While the pivotal point of adipose cytokine production is not yet known, the article makes clear that "The root cause of inflammation [is] obesity," with adverse effects reversed with weight loss. Know, however, that not all adiposity is equal, and visceral is, hands-down, the largest contributor to adipocytokine production when compared to subcutaneous.
As we look to the future of personalized pharmacology, "adipocytokine-based phamacotherapy for metabolic disease is on the horizon," and may include neutralizing IL-1 in order to improve insulin resistance and reduce inflammation or targeting JNK or IKK beta.
1. Surgery 2009;145:255-9
doi: 10.1016/j.surg.2009.09.038
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