Sugar, Uric Acid, and the Etiology of Diabetes and Obesity

Richard J. Johnson; Takahiko Nakagawa; L. Gabriela Sanchez-Lozada; Mohamed Shafiu; Shikha Sundaram; Myphuong Le; Takuji Ishimoto; Yuri Y. Sautin; Miguel A. Lanaspa


Diabetes. 2013;62(10):3307-3315. 

In This Article

Fructose-Induced Weight Gain and Metabolic Syndrome

Experimental studies from the 1950s showed the peculiar ability of fructose to induce insulin resistance in laboratory rats. Today, fructose intake has been shown to induce all features of metabolic syndrome in rats, as well as oxidative stress, endothelial dysfunction, fatty liver, microalbuminuria and kidney disease (rev. in.[1] Similar findings can be shown when animals are fed sucrose or high-fructose corn syrup (HFCS), both which contain fructose.[2,3] In contrast, administration of glucose or starch results in fewer features of metabolic syndrome when provided equivalent intake.[4,5]

Fructose may increase the risk for obesity by altering satiety, resulting in increased food intake. The intake of fructose is not effective in stimulating insulin and leptin secretion in humans, and hence may not induce a satiety response.[6] Other mechanisms may also be operative. For example, a high intake of fructose induces leptin resistance in rats.[7] Fructose also encourages food intake due to stimulation of dopamine in the mesolimbic system and effects on the hypothalamus.[8,9] Food intake is also stimulated by hepatic ATP depletion,[10] which occurs in animals and humans administered fructose.[11] Fructose may also affect metabolic rate. A recent study in humans documented a reduction in resting energy expenditure in overweight and obese subjects fed fructose but not glucose.[12]