The Fat Resistance Diet

How Does Inflammation Cause Leptin Resistance?  E-mail


How, exactly, does chronic inflammation cause leptin resistance? The question and the answer lie at the very heart of the Fat Resistance Diet.

Fat biology researchers have uncovered what many believe to be the key mechanisms of leptin resistance. Dr. Jeffrey Flier and his colleagues at Harvard Medical School have led these efforts. They have discovered that a group of molecules involved in reducing inflammation also interfere with leptin signaling on the cell surface and inside the cell. These molecules are known as SOCS, which stands for suppressors of cytokine signaling. Two specific SOCS molecules, SOCS-1 and SOCS-3, have been shown in many animal studies, first by Flier’s group and later by other research teams, to jam the signals that leptin is supposed to deliver to brain cells and muscle cells.


What is the significance of the fact that SOCS molecules are key causes of leptin resistance—the fundamental factor in stubborn overweight? SOCS-1 and SOCS-3 are both part of the body’s response to inflammation. When working properly, our levels of inflammation are kept in balance by overlapping feedback loops. When particular arms of the inflammation system go into gear, provoked, for example, by the presence of a bacterial invader or a sudden injury, another set of chemicals is released to make certain that the chemistry of inflammation doesn’t spiral out-of-control, causing excessive damage to cells and tissues. SOCS molecules represent the message-carriers in one of these negative feedback loops. Their message to inflammatory cells and cytokines is: "Cool down!" SOCS proteins are an essential part of the body’s system of checks and balances. When they work as they should, SOCS molecules succeed in checking excess inflammation. As inflammation subsides, levels of SOCS subside.

Immunobiologists believe that overweight people with chronic inflammation have chronically high levels of SOCS, released in a continual effort to damp down their body-wide inflammation. Indeed, elevated SOCS proteins have been found in the brain, liver, muscle, and to a lesser extent, the fat tissue of obese animals. High SOCS levels are a sign that the overweight animal is "over-inflamed" and trying to tone the inflammation down. Studies done at Harvard have found SOCS molecules in the hypothalamus, a walnut-sized structure at the base of the brain that regulates mood, thirst, and hunger. The Harvard studies show that SOCS-1 and SOCS-3 jam leptin’s signal at the internal portion of the leptin receptor. Bottom line: SOCS molecules interrupt leptin’s message to suppress hunger, and they are primary causes of leptin resistance in the brain.


Other studies suggest that SOCS-1 and SOCS-3 also interfere with leptin’s effects in muscle and other organs outside the brain. In these sites, jamming of the leptin signal can lead to sluggish metabolism. Remember, an active SOCS system is strong evidence that the person is already suffering from chronic inflammation that the body is trying to get under control. 

Adding more fuel to the fire of inflammation’s role in fat, another research team from Harvard’s Joslin Diabetes Center showed that the exact same molecules, SOCS-1 and SOCS-3, play a distinctly similar role in hampering insulin sensitivity. Their research, published in 2004, demonstrated how these molecules trigger insulin resistance by interfering with the successful connection of insulin to its matching receptor on the surface of your cells. 

Under the influence of chronic inflammation, hormones that should function to protect your health are thrown into disarray. As their levels increase, they begin to destroy your health, encouraging weight gain and more inflammation. If you have a chronic weight problem, this is the vicious cycle you face whenever you try to lose weight and keep it off. Don’t ever let anyone tell you that weight problems are not the result of hormones. They are totally dependent upon hormones that misfire. Breaking the vicious cycle of obesity, inflammation and hormone disruption is the greatest nutritional challenge in the world today. 

Drugs will not fix this problem. The problem with drugs is: there aren’t any that do the right thing. Drugs that are used to treat the kind of inflammation associated with pain, like aspirin and ibuprofen, don’t act on the part of inflammation that produces hormone resistance. At high doses, they cause fluid retention, which only increases the bloating you feel.

There is something that can counter the kind of inflammation associated with obesity: FOOD.

A major problem of the modern, obesity-causing diet—often overlooked—is that the natural, inflammation-fighting components of food have been removed. It’s true that our food supply is loaded with concentrated high calorie ingredients, like added sugar and added fats, which are easy to slurp down. Just as important is what has been removed from our food: nutrients that fight inflammation. What are they? There are two major categories: GOOD FATS and PHYTONUTRIENTS.



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