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While the detrimental effect of refined sugars on health has been the subject of many investigations, little is known about the long-term impact of natural sweeteners on metabolic disorders. In this study we compared the metabolic responses to chronic ingestion of refined sugars compared to various natural sweeteners in diet-induced obese rats. Wistar rats were fed a high-fat high-sucrose diet (HFHS) for 8 weeks and daily gavaged with a solution containing 1 g of total carbohydrates from refined sugar (sucrose or fructose) or six different natural sugar sources, followed by assessment of glucose homeostasis, hepatic lipid accumulation, and inflammation. While glucose tolerance was similar following treatments with refined and natural sugars, lowered glucose-induced hyperinsulinemia was observed with fructose. Consumption of fructose and all-natural sweeteners but not corn syrup were associated with lower insulin resistance as revealed by reduced fasting insulin and homeostatic model assessment of insulin resistance (HOMA-IR) compared to sucrose treatment of HFHS-fed rats. All-natural sweeteners and fructose induced similar liver lipid accumulation as sucrose. Nevertheless, maple syrup, molasses, agave syrup, and corn syrup as well as fructose further reduced hepatic IL-1β levels compared to sucrose treatment. We conclude that natural sweeteners and especially maple syrup, molasses, and agave syrup attenuate the development of insulin resistance and hepatic inflammation compared to sucrose in diet-induced obese rats, suggesting that consumption of those natural sweeteners is a less harmful alternative to sucrose in the context of obesity.

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Differential Effects of Chronic Ingestion of Refined Sugars versus Natural Sweeteners on Insulin Resistance and Hepatic Steatosis in a Rat Model of Diet-Induced Obesity