More on fructose and obesity

There seems to be a fairly straightforward pathway here:

1. Eating fructose causes the body to make high levels of triglycerides (1)
2. High levels of triglycerides cause leptin resistance, by an unknown mechanism (2)
3. Leptin resistance causes hyperphagia (overeating), presumably due to increased hunger
4. Overeating causes obesity

It is reasonable to think that anyone who expresses the fructose receptor on their liver will get leptin resistance and thus, will get fat, if they eat enough fructose. I have heard that not everyone does express the fructose receptor and people that don't have it don't get fat, but I haven't found the reference. I'll post it if I do.

At any rate, for a given level of fructose processing, increasing ingestion of fructose would increase TG output, thus increasing leptin resistance. Thus, with a reasonable level of certainty, eating large amounts of sugar or HCFS will make people fat. How much it takes would depend on the person and how much of the fructose they process.

Then the situation becomes self-reinforcing. If the person quits eating sugar, there is still a lot of fat stored up. If it is released, the TG level would be high, causing the leptin resistance to remain, causing the high levels of eating to continue, so the fat cells continue to be full. Exercise might help with this (my guess) by burning off the fat as it is mobilized.

In other words, the best way to avoid being fat is to not go there in the first place. A good way to do that is to not eat sugar, at least in large amounts. A piece of pie at Thanksgiving, or ice cream on the 4th of July would be fine for people with normal metabolism. None may be a good amount for those with damaged metabolism, so the problem has a chance of not getting worse.


1: Fructose: Metabolic, Hedonic, and Societal Parallels with Ethanol
2: Leptin and the Control of Body Weight: A Review of Its Diverse Central Targets, Signaling Mechanisms, and Role in the Pathogenesis of Obesity