(30-03-11) Prevention and reversal of diet-induced leptin resistance with a sugar-free diet despite high fat content.

Shapiro A, T??mer N, Gao Y, Cheng KY, Scarpace PJ.

Department of Pharmacology and Therapeutics, University of Florida, College of
Medicine, Box 100267, Gainesville, FL 32610, USA.
Abstract
Chronic consumption of a Western-type diet, containing both elevated sugar and
fat, results in leptin resistance. We hypothesised that fructose, as part of
the sugar component of Western-type diets, is one causative ingredient in the
development of leptin resistance and that removal of this component will
prevent leptin resistance despite high fat (HF) content. We fed rats a sugar-
free (SF), 30 % HF (SF/HF) diet or a 40 % high-fructose (HFr), 30 % HF (HFr/HF)
diet for 134 d. The HFr/HF diet resulted in impaired anorexic and body-weight
responses to both peripherally (0??6 mg/kg, assessed on day 65 of the diet) and
centrally (1??5 ??g/d, assessed on days 129-134) administered leptin, whereas
SF/HF-fed rats were fully leptin responsive. At day 70, half the HFr/HF-fed
animals were switched to the SF/HF diet, reversing the leptin resistance
(assessed 18 d after the diet switch). The HFr/HF diet elevated serum leptin
and reduced adiponectin, and levels were restored abruptly at day 3 after
switching to the SF/HF diet. These data demonstrate that a diet containing both
HFr and fat leads to leptin resistance, while an isoenergetic SF/HF diet does
not. Moreover, removal of fructose from this diet reverses the leptin
resistance and the elevated leptin, suggesting a cause-and-effect relationship.
These data suggest that fructose is the bioactive component of a HF/high-sugar
diet that is essential for the induction of leptin resistance.

Source: Br J Nutr. 2011 Mar 22:1-8. [Epub ahead of print]

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