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Dr. Leo Galland's New Fat Resistance Diet™

Using Food to Combat Leptin Resistance, the Underlying Cause of the Obesity Epidemic

By Leo Galland, M.D.

SUMMARY: Chronic obesity results from resistance to leptin, an auto-regulatory fat-derived hormone, or adipokine. The major cause of leptin resistance appears to be the chronic low-grade inflammation that is associated with obesity. This vicious cycle, weight gain—inflammation—leptin resistance—increasing obesity, can be broken by a weight loss diet built around anti-inflammatory foods. An annotated scientific bibliography supporting this dietary approach, with sample menus and recipes, can be found in my new book The Fat Resistance Diet™.

The discovery that fat cells produce hormones (adipokines) revealed that fat is a biologically active tissue, not simply an inert storehouse of unused calories. Through the actions of adipokines, excess fat by itself can cause hypertension, diabetes, cardiovascular disease, cancer, stroke and osteoarthritis. More important, by producing adipokines, fat regulates itself. Adipokines can increase or decrease appetite and metabolic rate, making weight control easier or harder.

Leptin, the first adipokine, informs the brain of the size of the body's fat stores, functioning as part of a negative feedback loop. When an animal or human is overfed and begins to gain weight, the increase in body fat leads to increased leptin synthesis, which in turn suppresses appetite and stimulates fat burning, helping to restore normal weight. The more body fat, the higher the circulating levels of leptin. Obesity results from the failure of leptin signaling, a condition called leptin resistance, which is analogous to the insulin resistance that underlies type 2 diabetes. When scientists at the University of Texas developed a breed of rats that were genetically protected against developing leptin resistance, they found that they could force feed the rats without making them obese. In all other respects, these rats were the same as controls.

For humans, the major cause of leptin resistance appears to be chronic inflammation, a biochemical state induced in the body through the actions of cytokines, prostanoids, kinins and other inflammatory molecules. Obesity itself adds to inflammation, because fat tissue produces inflammatory cytokines like TNF-alpha and interleukin-6. Chronically overweight people suffer from a vicious cycle of inflammation, leptin resistance, obesity, more inflammation, greater weight gain. In this cycle, inflammation causes leptin resistance indirectly, by stimulating the synthesis of blocking molecules called suppressors of cytokine signaling (SOCS).

To limit the damage produced by the inflammatory response, the body offers a counter-regulatory, anti-inflammatory response, spearheaded by anti-inflammatory SOCS molecules. SOCS-1 and SOCS-3 interfere with cells' ability to respond to leptin. SOCS-3 also blocks the response to insulin and is a key factor in insulin resistance.

The SOCS counter-regulatory response is a major cause of leptin resistance and a major factor in the development of obesity. To turn off the production of SOCS chemicals that cause leptin resistance, one has to turn off the inflammation that causes cells to make them. Research on several fronts has shown that inflammation is promoted by dietary factors that include trans-fatty acids, saturated fat, a high omega-6/omega-3 ratio, refined carbohydrates and a corresponding lack of dietary fiber. Inflammation is also promoted by exposure to environmental pollutants like organochlorines and phthalates.

I designed the Fat Resistance Diet™ as an anti-inflammatory weight loss diet, enriched with foods that reverse leptin resistance by combating inflammation. Omega-3 fats, fiber, polyphenols, carotenoids, isothiocyanates and sulfides are abundant. Saturated and omega-6 fats and the glycemic load are carefully controlled. To make this diet appealing and attractive, I asked Jonathan Galland, a gourmet cook, to design and test delicious, easy to prepare recipes and meal plans based on classic American and international favorites, adapted to meet exacting standards of nutritional quality. The food elevates the science and makes it practical.