Controlling Weight

Controlling weight is affected by so many physiological factors it's sometimes difficult to keep track. Before 1994, when leptin was discovered, people thought weight control was simply a matter of willpower. Now we know better.

Most of us know that leptin is secreted by fat cells when we have had enough to eat and the fat cells are full, and the leptin turns down our appetite. Children born without leptin have voracious appetites and become obese as toddlers; when given leptin, they slim down. People with no leptin are rare, but overweight people may have leptin resistance, just as people with type 2 diabetes have insulin resistance. In both cases, levels of the hormones can be high but the body doesn't respond to them properly.

On the other hand, the hormone ghrelin is produced by the stomach when we haven't eaten, and it makes us hungry.

Now a third hormone has been discovered that increases appetite during fasting and decreases it during feeding. It has been named neurosecretory protein GL, usually referred to simply as NPGL.
This hormone not only affects appetite, but it also increases the storage of fat, even on a low-calorie diet.

Another study found a gene with the snappy name GTRAP3-18 that helps to regulate both food intake and glucose levels. Mice without this gene were both lean and hypoglycemic, and this was due to neither less activity nor an increased metabolism, but rather to eating less. The authors suggested that the gene could be a target for drugs, saying, "Eating too much or too little could actually be a genetic problem," although we know that other factors such as emotions and the food environment can play a role as well.

A third study found yet-another protein with a snappy name, MKK6, that affects weight by stimulating the burning of fat to generate heat. Overweight people seem to have higher levels of MKK6, which hinders the conversion of white fat cells into brown fat cells. White fat cells store fat, and brown fat cells burn fat.

A fourth study described brain cells called tanycytes that detect nutrients and tell us when we've eaten enough. Foods high in certain amino acids (the building blocks of protein) activate the tanycytes and make us feel full sooner, which is consistent with the commonly stated fact that protein is satiating. Interestingly, the receptors in the tanycytes are the same as those in the tongue that detect the umami flavor of protein foods.

The two amino acids that react the most with the tanycytes are arginine and lysine. Foods rich in these amino acids include pork shoulder, beef sirloin, chicken, mackerel, plums, apricots, avocados, lentils and almonds.

Finally, a Swiss study showed that severely obese people release fewer satiety hormones than people of normal weight because they have fewer of the intestinal cells that produce the satiety hormones than normal-weight people. Weight-loss surgery seems to increase the number of these cells.

We all know that weight loss, and especially maintenance of weight loss, is difficult. One reason is that there are so many factors involved (and I'm sure even more will be found in the future), and different people may have deficits in different systems.

In fact, an Israeli study showed that the glycemic index of various foods could vary a lot between individuals. A food that was problematic for one person might be fine for another. And for some individuals, even white bread seems to be better for blood sugar levels than whole grain bread.

Even the bacteria in your gut may affect whether or not you will lose weight on a diet with a lot of fruits, vegetables, fiber, and whole grains, according to a Danish study. So if some recommended diet doesn't work for you, it may not be that you're "doing it wrong." It may be that the diet isn't the right one for you.

What this all means is that it's up to us to take charge and find out which diets are best for our personal physiology. It's a lot more work than simply following guidelines set by some "diet expert." But it's worth the effort.

And it's encouraging that so much research is going into what factors govern appetite and fat gain or loss. In the long run, this basic research should lead to real solutions. Let's hope funds for basic research aren't cut any more in a misguided effort to save money. In the long run, figuring out the best way for people to lose weight and keep it off will save even more money from health care expenses than the costs of the research.