Fructose-Induced Leptin Resistance Study

Most low carbers are aware of the fact that high fructose corn syrup is associated with obesity. And that the problem is the fructose. But since fructose doesn't raise insulin levels, how does fructose do that?

I ran into an interesting study the other day while researching high fructose corn syrup. The running title is: Fructose and Leptin Resistance, and the hypotheses was 2-fold. 1) Chronic high fructose intake induces Leptin Resistance; and 2) Leptin Resistance leads to susceptibility to weight gain.

In the study, 23 male Sprague-Dawley rats, age 2-1/2 months, were first fed one of two diets: 1) 5.2% fat (lard), 60% corn starch, 18.3% protein (mostly casein), and 3.6 kcal/g; or 2) 5.2% fat (lard), 60.4% fructose, 18.8% protein (mainly casein), and 3.6 kcal/g. Since the hypotheses dealt with Leptin Resistance, all of the rats were tested with Leptin injections prior to putting them on the diets, and all of the rats responded to those injections by reducing their 24 hr food intake.


At 6 months, the rats were tested again. There was no noticeable difference between the fructose-fed rats and the control group in regards to food intake, (total food was left for them in the morning, and they were able to eat as much of it as they wanted, whenever they wanted), body weight, fat storage, blood leptin level, and metabolic syndrome markers except for raised Triglyceride levels in the blood of those rats on the high fructose diet.

All rats were again injected with leptin, but only the rats on the control group diet reduced their 24 hour food intake this time. The fructose-fed rats didn't respond to leptin at all. Plus other tests on the fructose-fed rats showed they all had Leptin signalling issues. So it wasn't just a matter of higher Triglycerides interfering with Leptin's ability to cross the Blood Brain Barrier. Though that was most likely a factor as well.

At this point, 1/2 of the fructose-fed rats and 1/2 of the control group rats were placed on a high-fat diet of 60% kcal/g from lard, to replace the fructose, 7% kcal/g from sucrose, and 5.24 kcal/g. They didn't say what the protein intake was, but I suppose it was the same.

At 2 weeks, the rats were tested again, but this time there were significant differences. Both the control group and fructose-fed rats now eating a high-fat diet increased their food intake and therefore incurred significant weight gain. But the rats previously fed a high-fructose diet demonstrated higher calorie intake, higher weight gain, and higher fat storage.

While glucose and insulin levels were not affected in any of the rats, in non-fasted blood samples, uric acid levels increased in all rats being fed the high-fat diet, but not in those on just high fructose. Triglycerides were elevated with the high fructose diet, but not in those on no-fructose high-fat. This showed that a high-fat diet didn't affect Triglycerides, while fructose feeding doubled Triglyceride levels. Plus, as body fat storage went up, so did Triglyceride levels.

The study is significant because it shows Leptin Resistance to be at the heart of the current Obesity Epidemic, possibly driven by a high fructose intake then coupled with an excess intake of calories/fat, and that Insulin Resistance does not cause obesity.

Now before you start screaming that this study is flawed and throw it out because you don't like the idea that a high-fat diet led to excess fat storage, and increased Triglycerides and uric acid, keep in mind that the diet also contained a 7% sugar intake. Plus it's extremely possible that the same results would have occurred with any kind of excess of calories.

Leptin Resistance plus a high-fat diet together may or may not be significant. It's still too early to know for sure.