OFFICE OF SCIENCE OUTREACH
DEPARTMENT OF BIOLOGY
Obesity, Type 2 Diabetes, and Fructose
Part 3: The Consequences of a High-Fructose Diet
1. Elevated Triglycerides
When fed fructose, the liver builds fatty acids and assembles them into triglycerides. It exports the triglycerides into the bloodstream, so that they can be taken up by fat cells for storage. The triglyceride-carrier protein is LDL, known as "bad cholesterol." It's a carrier of cholesterol, which attains a lower density by carrying additional triglycerides (which, being less dense than water or protein, make the carrier a "low-density" carrier protein.) Elevated triglycerides and cholesterol are associated with heart disease. Triglycerides are a part of the "metabolic syndrome" disease, which eventually manifests itself as Type 2 Diabetes.
2. Fatty Liver
The transporter in liver cells, that moves triglycerides from the inside of the cell to the outside, and thus into the bloodstream, can only work so fast. If triglycerides are produced faster than the transporter can export them, the triglycerides build up inside liver cells. They form fat droplets. The liver accumulates fat. Now, in force-fed geese, fatty liver is called foie gras, but fatty liver is not what we want to have. Fatty liver is another of the pre-disposing factors to Type 2 Diabetes.
3. Increased Fat Storage
Fructose also leads to alterations in the handling of dietary fat. This has been shown directly in mice. There are significant differences in mice fed identical diets, but with some having their diet supplemented with glucose and others having a supplement of fructose in the same caloric quantity. The glucose-fed mice, when subsequently given fat, metabolize the fat in the production of ATP (as illustrated above). The fructose-fed mice don't do this; they import the fat directly into fat cells for storage. Apparently, fructose not only is converted to fat by the liver, but it changes the way dietary fat is handled. The result is that a diet rich in fructose and fat leads to significant weight gain. This is particularly worrisome, given Americans' increased consumption not only of sugars ↑ but of fats ↑.
4. Leptin Insensitivity
There must be an explanation for this unusual effect of fructose on the storage vs metabolism of dietary fat. At present, it appears that fructose, by some mechanism, makes the brain insensitive to the hormone, leptin.
Leptin is a hormone that is produced by fat cells, more-or-less constantly. The more fat cells there are, the more leptin there is. Normally, the brain registers the concentration of leptin in the bloodstream, and releases a variety of hormones to adjust metabolic rate. This is, presumably, a part of the mechanism by which people maintain a fairly constant weight despite fluctuations in the amount of food they eat. When we eat more, and store more fat, our leptin concentration rises. The brain signals our bodies to turn up the rate of metabolism, to use up some of that extra fat. When we eat less, and our quantity of fat decreases. our leptin concentration goes down. The brain signals our cells to slow down metabolism, and not use up the little fat we have left. This is the "thrifty metabolism" we hear about, wherein metabolism slows down and it's just plain hard to lose that extra weight.
The brain's modulation of metabolic rate includes not only the rate at which sugars and fatty acids are metabolized to CO2 and water to drive ATP production; it also includes the behavior of fat cells. When the brain signals to speed up metabolism, fat cells respond by breaking down fat for other cells to metabolize. When the brain signals to slow down metabolism, fat cells respond by taking up fat and storing it. By modulating both metabolic rate and fat storage vs mobilization, the complete signalling system assures that the body does not become either overloaded with fat or totally depleted of it.
With a high-fructose diet, the brain becomes insensitive to leptin. Being unable to recognize that leptin is present, the brain responds as if there are far too few fat cells, as if the body is starving. The brain continuously signals to turn down the rate of metabolism, and to store any fat that happens to be in the food. Hence, a high-fructose diet leads to fat storage.
So not only does fructose lead to highly-efficient storage of dietary fat, it leads to the production of fat by the liver. Together, these phenomena are a double-whammy: fat is both made and stored with high efficiency. Weight gain would seem inevitable.
Because fat (triglycerides) is being made by the liver, and not fat cells themselves, the fat must be transported through the bloodstream to the fat cells. This elevates triglyceride levels, a third-whammy that starts one down the road to Type 2 Diabetes.
Because the liver may well produce triglycerides faster than it can export them, it may well accumulate fat droplets. This is fatty liver, the fourth-whammy that sends one further down the road to Type 2 Diabetes.
← Molecular Biology Consequences of a High-Fructose Diet Sources of Fructose →
Contact J. Jose Bonner, OSO Director
last updated: August 24, 2010