title: Prevention and reversal of diet-induced leptin resistance with a sugar-free diet despite high fat content.
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 μg/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.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Florida, College of Medicine, Box 100267, Gainesville, FL 32610, USA. sasha1@ufl.edu
authors.forename: Alexandra
authors.initials: A
authors.lastname: Shapiro
authors.forename: Nihal
authors.initials: N
authors.lastname: Tümer
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Gao
authors.forename: Kit-Yan
authors.initials: KY
authors.lastname: Cheng
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Scarpace
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D000855:Anorexia / Q000209:etiology; D001066:Appetite / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D004041:Dietary Fats / Q000008:administration & dosage* / Q000009:adverse effects; D019422:Dietary Sucrose / Q000009:adverse effects*; D005632:Fructose / Q000009:adverse effects*; D020738:Leptin / Q000378:metabolism*; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D052242:Adiponectin; D004041:Dietary Fats; D019422:Dietary Sucrose; D020738:Leptin; D005632:Fructose