Obesity—A Disease With Many Aetiologies Disguised in the Same Oversized Phenotype

Has the Overeating Theory Failed?

Peter Stenvinkel


Nephrol Dial Transplant. 2015;30(10):1656-1664. 

In This Article

Fructose Resemble Alcohol

In contrast to its isomer glucose, fructose is not important for biochemical reactions. Thus, we can manage without it and in nature fructose is always paired to glucose. Intake of fructose can induce all the features of the metabolic syndrome independent of excessive energy.[34,35] In pair-fed rats given either glucose or fructose as part of their diet, rats fed fructose are more prone to develop metabolic syndrome.[36] This finding is confirmed by a study in humans comparing glucose with fructose-sweetened beverages, which showed that in overweight/obese adults dietary fructose promotes dyslipidaemia, increases hepatic lipogenesis, decreases insulin sensitivity and increases visceral adiposity.[37] Moreover, fructose metabolites not only promotes reactive oxygen metabolites and overwhelm the hepatic mitochondrial capacity but also drives excessive food consumption by stimulation of dopamine, affecting the reward system in the brain.[38] Lustig[38] proposed that fructose in many ways mimics the effect of its metabolic cousin ethanol, another non-essential energy source. The disease profile of ethanol and fructose is quite similar and both have chronic detrimental effects on long-term health.[38] In contrast to glucose, fructose causes intracellular adenosine triphosphate (ATP) depletion,[39] leptin resistance,[40] blocks satiety signals[41] and reduces resting energy expenditure.[42] In a recent study based on National Health and Nutrition Examination Survey, it was demonstrated that most US adults consume more sugar than is recommended and that there was a strong relationship between consumption of added sugar and increased risk for CVD mortality.[43] As carbohydrates with a high glycaemic index increase the risk for metabolic syndrome and obesity[44] as well as CVD,[43] it is believed that increased intake of energy-dense food is the main culprit. Recent data show that glucose induces obesity and insulin resistance via its conversion to fructose in the liver.[16] A study of 55 000 Swedish women supports the hypothesis that not all calories are equal.[45] Whereas 40% of the omnivores were overweight, elevated BMI was only found in 25% of the vegetarians.[45] Taken together, fructose has detrimental effect on metabolism and increases fat mass independent of energy intake.