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.

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.…”

Critically Discuss the Revival of Leptin for Obesity Therapy

“…These obese patients are hypothesized to develop leptin resistance that is commonly defined by the reduced capability of leptin to resist the development of obesity (Enriori et al, 2006;Morrison, 2008;Myers et al, 2008;Bjorbaek, 2009;Morris & Rui, 2009;Wong et al, 2013). Since the lack of response to leptin hinders cen- (Munzberg et al, 2005), and the type of diet (Shapiro et al, 2011), may also contribute to leptin resistance.…”