|Inflammation - Obesity|
One of the more radical research findings in fat biology suggests that fat cells are actually cousins of macrophages. It appears that very young fat cells (called pre-adipocytes) can be transformed into TNF-spewing macrophages, rather than maturing into normal adipocytes. A group of French researchers discovered that pre-adipocytes become macrophages when prompted to do so by cytokines. Their finding is another example of the dynamic complexity of fat. Fat cells are intimately connected to and sometimes interchangeable with cells of the immune system. They both create and react to a wide range of hormones and mediators. Fat can be thought of as part of the immune system and part of the endocrine (hormone) system. TNF, in fact, is both a cytokine (a mediator produced by macrophages) and an adipokine (a hormone produced by fat cells). Whatever its source, TNF and its inflammatory relatives can wreak havoc with our fat-storage-and-management systems. TNF interferes with the operation of insulin, and is therefore a major contributor to insulin resistance. So, too, is another adipokine called resistin.
What we see in obesity is the swelling of fat tissue accompanied by a cacophony of cellular activity, most of it pushing the body toward a state of excess inflammation. Among the pro-inflammatory substances made by fat cells themselves are leptin, TNF, IL-6, and resistin. Add the contribution of fat-embedded macrophages and their own payload of TNF and IL-6, and biologists are beginning to view fat as a brewery of inflammatory chemicals.
The whole body is affected by this state of affairs, since inflammatory activity is not limited to fat tissue but spills over into the bloodstream. Thus, overweight people become subject to a body-wide state of chronic, low-grade inflammation, induced by fat itself.
The effect of fat on inflammation is just half of the cycle. The effects of inflammation on fat are equally intense. When inflammation is severe, as in a life-threatening infection, it can cause tremendous weight loss. With severe inflammation, the body cannibalizes itself and both fat and muscle cells are destroyed. This is not a good way to lose weight. The breakdown of muscle is always greater than the breakdown of fat.
One marker of inflammation that has received considerable attention over the past two years is "C-reactive protein" or CRP. Mild elevation of the level of CRP in blood is associated with obesity and with weight gain. Weight loss, on the other hand, produces a decrease in CRP. In people with a history of heart disease, mild elevation of CRP predicts an increased risk of heart attacks and strokes. In adults who develop diabetes, elevated CRP occurs before the onset of diabetes. In people with normal blood pressure, elevated CRP predicts the future development of high blood pressure. In aging adults, high CRP is associated with muscle weakness and frailty. Studies of CRP have proven the close relationship between silent, chronic inflammation and the development of the most common chronic diseases of modern society.
Inflammation and fat share a complex relationship. When inflammation is severe, as in a life-threatening infection, it can cause tremendous weight loss. With severe inflammation, both fat and muscle cells are destroyed; the breakdown of muscle is always greater than the breakdown of fat. When inflammation is mild and chronic, however, producing few symptoms and only subtle changes on blood tests, inflammation has a very different effect on your metabolism. It disrupts hormones. Acting through the complex networks of chemicals involved in homeostasis, inflammation makes your cells resistant to the normal regulatory effects of leptin and other hormones, including insulin and cortisol. I’ll say more about insulin and cortisol later. These hormones are not adipokines, but they can have a devastating effect on your attempts to lose weight. First, I want you to understand the vicious cycle that keeps you from living lean: FAT ITSELF CAUSES INFLAMMATION.
Many adipokines, even leptin itself, are chemical mediators of inflammation. Remember what I said about mediators. They are chemicals associated with inflammation that actually cause damage to cells. The more fat in your body, the higher the levels of these mediators in your blood and the greater the level of inflammation in your body. Not only does this fat-derived inflammation prevent leptin from helping you lose weight, it causes other hormonal effects that interfere with permanent weight loss. Inflammation raises the level of insulin and cortisol, two hormones that actually cause your body to make more fat.