Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding

Abstract

RJ, Scarpace PJ. Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding. Am J Physiol Regul Integr Comp Physiol 295: R1370 -R1375, 2008. First published August 13, 2008 doi:10.1152/ajpregu.00195.2008.-It has been suggested that increased fructose intake is associated with obesity. We hypothesized that chronic fructose consumption causes leptin resistance, which subsequently may promote the development of obesity in response to a high-fat diet. Sprague-Dawley rats were fed a fructose-free control or 60% fructose diet for 6 mo and then tested for leptin resistance. Half of the rats in each group were then switched to high-fat diet for 2 wk, while the other half continued on their respective diets. Chronic fructose consumption caused leptin resistance, while serum leptin levels, weight, and adiposity were the same as in control rats that were leptin responsive. Intraperitoneal leptin injections reduced 24-h food intake in the fructose-free group (73.7 Ϯ 6.3 vs. 58.1 Ϯ 8 kcal, P ϭ 0.02) but had no effect in fructose-fed rats (71.2 Ϯ 6.6 vs. 72.4 Ϯ 6.4 kcal, P ϭ 0.9). Absence of anorexic response to intraperitoneal leptin injection was associated with 25.7% decrease in hypothalamic signal transducer and activator of transcription 3 phosphorylation in the high-fructose-fed rats compared with controls (P ϭ 0.015). Subsequent exposure of the fructose-mediated, leptin-resistant rats to a high-fat diet led to exacerbated weight gain (50.2 Ϯ 2 g) compared with correspondingly fed leptin-responsive animals that were pretreated with the fructose-free diet (30.4 Ϯ 5.8 g, P ϭ 0.012). Our data indicate that chronic fructose consumption induces leptin resistance prior to body weight, adiposity, serum leptin, insulin, or glucose increases, and this fructose-induced leptin resistance accelerates highfat induced obesity.

Comparing the Effects of Inorganic Nitrate and Allopurinol in Renovascular Complications of Metabolic Syndrome in Rats: Role of Nitric Oxide and Uric Acid

“…Regarding insulin resistance, our results were in accordance with previous studies which suggested that insulin resistance or hyperinsulinemia is associated with metabolic syndrome [38], enhanced urate reabsorption and reduced urate excretion in the kidney, leading to elevated serum uric acid concentrations [39]. Consistent with this observation is the finding that drugs which improve insulin sensitivity and lower insulin levels also reduce the level of serum uric acid in diabetic patients [40].…”

Opposing effects of fructokinase C and A isoforms on fructose-induced metabolic syndrome in mice

“…Our group has also shown that fructose (or sucrose) can exacerbate features of metabolic syndrome compared with pair-fed glucose-or starch-fed controls, even under settings of caloric restriction (9)(10)(11). Thus, whereas fructose intake may induce leptin resistance with impaired satiety and weight gain (12,13), fructose-induced metabolic syndrome may also occur, independent of increases in energy intake or weight gain.…”

New Insights on the Risk for Cardiovascular Disease in African Americans

“…[109][110][111][112] The ability of fructose to cause obesity is not simply from its caloric value but rather from its capacity to induce leptin resistance (thereby blocking satiety responses) while at the same time reducing ATP production by blocking fat oxidation. 109,[113][114][115] Laboratory animals fed fructose develop features of metabolic syndrome and, if prone, will even develop diabetes. 116,117 Features of metabolic syndrome can be induced even with caloric restriction provided the sugar (or fructose) content is high, 116 demonstrating that it is not overnutrition but rather the presence of fructose that is responsible for the development of metabolic syndrome.…”