Effects of sugar solutions on hypothalamic appetite regulation

Abstract: Several hypotheses for the causes of the obesity epidemic in the US have been proposed. One such hypothesis is that dietary intake patterns have significantly shifted to include unprecedented amounts of refined sugar. We set out to determine if different sugars might promote changes in the hypothalamic mechanisms controlling food intake by measuring several hypothalamic peptides subsequent to overnight access to dilute glucose, sucrose, high fructose corn syrup, or fructose solutions. Rats were given access to food, water and a sugar solution for 24 h, after which blood and tissues were collected. Fructose access (as opposed to other sugars that were tested) resulted in a doubling of circulating triglycerides. Glucose consumption resulted in upregulation of 7 satiety-related hypothalamic peptides whereas changes in gene expression were mixed for remaining sugars. Also, following multiple verification assays, 6 satiety related peptides were verified as being affected by sugar intake. These data provide evidence that not all sugars are equally effective in affecting the control of intake.


Alex’s Notes: It’s worth asking what effects various sugars have on the brain, and while there are many studies examining the effects of one sugar or another on difference areas of the brain, no study has looked at the effects of various sugars on any one brain area. Thus, the current study set out to compare the efficacy of fructose with high fructose corn syrup (HFCS-55), sucrose and glucose in altering the regulation of several of hypothalamic mechanisms that are known to control food intake.

The study was performed on rats who had unlimited access to food and water. They were divided into one of five groups after a one-week control diet period where everything was normal for a rat. The groups were a control group that maintained the standard diet, or a group with sugar-sweetened water (fructose, glucose, HFCS, or sucrose). Once the rats were switched to the experimental diets, they were sacrificed after 24 hours.

There was no difference in weight among any of the rats after the 24 hour period, which should not be a surprise given the experimental period was only 24 hours. However, all four sugar groups did consume significantly less chow but significantly more calories than the control group.






Cholecystokinin (CCK)





Corticotropin Releasing Hormone (CRH)





Growth Hormone (GH)










Tumor Necrosis Factor alpha (TNF-α)





Thyrotropin Releasing Hormone (TRH)





As for the brain, the only significant changes observed in the glucose fed group were up-regulations in anorectic genes, whereas other sugars promoted both up- and down-regulations. This may perhaps speak to the evolutionary significance of glucose in promoting satiety. Moreover, none of the significant changes observed in the sucrose group were significant in the HFCS group, which given their similar composition may be owed to the fact that sucrose is bound glucose + fructose, while HFCS is these sugars in their free form.



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