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APPETITE, OBESITY, AND DIGESTION

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

¹Department of Pharmacology and Therapeutics and ²Division of Nephrology, Hypertension, and Transplantation, University of Florida, College of Medicine, Gainesville, Florida

Submitted 17 March 2008 ; accepted in final form 7 August 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 ± 6.3 vs. 58.1 ± 8 kcal, P = 0.02) but had no effect in fructose-fed rats (71.2 ± 6.6 vs. 72.4 ± 6.4 kcal, P = 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 = 0.015). Subsequent exposure of the fructose-mediated, leptin-resistant rats to a high-fat diet led to exacerbated weight gain (50.2 ± 2 g) compared with correspondingly fed leptin-responsive animals that were pretreated with the fructose-free diet (30.4 ± 5.8 g, P = 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 high-fat induced obesity.

obesity

This article has been cited by other articles:

				M. Matheny, Y. Zhang, A. Shapiro, N. Tumer, and P. J. Scarpace Central overexpression of leptin antagonist reduces wheel running and underscores importance of endogenous leptin receptor activity in energy homeostasis Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2009; 297(5): R1254 - R1261. [Abstract] [Full Text] [PDF]

				P. J. Scarpace and Y. Zhang Leptin resistance: a prediposing factor for diet-induced obesity Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2009; 296(3): R493 - R500. [Abstract] [Full Text] [PDF]

				J. R. Vasselli Fructose-induced leptin resistance: discovery of an unsuspected form of the phenomenon and its significance. Focus on "Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding," by Shapiro et al. Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2008; 295(5): R1365 - R1369. [Full Text] [PDF]