Chronic Exposure To Artificial Sweeteners Induced Changes In Glucose Tolerance And Its Molecular Mechanism

Prevalence of obesity and related metabolic diseases has seriously threatened the human health, which come from the imbalance between energy intake and consumption. One of the vital causes leading obesity is the over intake of high-calories foods. High-intensity artificial sweeteners are widely used in the food industry to limit the intake of high-sugar, but its safety has been questioned in recent years. Recent progress in unraveling taste sensing mechanism has showed sweet taste receptors not only existed in the oral cavity, but also widely distribute in other digestive organs, including the gastrointestinal tract. It is possible that these taste receptors can sense basic tastes in much the same way as the tongue, which is related with energy metabolism. On basis of sweetness and sweet receptor, using ICR adult mice as experimental subjects with chronic exposure to sweeteners and gustatory behavior (two-bottle preference test), whole lingual epithelium fixing, frozen sections, HE staining, q-PCR and ELISA techniques were used to explore the correlation among sweetness of artificial sweeteners, glucose metabolism and intestinal sweet taste receptors. The results are as follows:(1) Determination of sweetness of sweetenersSweetness preference curves to sucrose, sucralose, AK were obtained by TBP test. On the basis of previous laboratory results and combined with literature, sweetness chronic exposure to sucrose/AK sugar/sucralose were3,5,8,11.5,15, which calculated from the sweetness1of2%sucrose solution.(2) Artificial sweeteners chronic exposure increase body weight in miceAfter chronic exposure to sweet, three sweeteners groups showed similar trends-body weight growth with sweetness increased. The bodyweight of sucrose11.5,15sweetness teams, AK11.5,15sweetness teams, sucralose15sweetness team mice were significantly higher than the control mice. Solution consumption was in accordance with the sweetness preference curve obtained by preliminary experiments and mice showed similar response to the equivalent sweetness of artificial sweeteners solution In the aspect of food intake, sucralose and AK groups mice did not differ obviously from the control group, but higher than sucrose group.(3) Chronic artificial sweeteners exposure change the glucose tolerance and insulin secretionThree sweeteners showed similar trends, the low sweetness (sweetness3,5,8) teams mice enhanced glucose tolerance, and the high sweetness (sweetness11.5,15) mice progressively decreased in glucose tolerance. The sucrose11.5,15sweetness teams mice displayed impaired glucose tolerance from the mid-term stage to the end of exposure. Sucralose15sweetness team and AK11.5,15sweetness teams mice also appeared glucose intolerance at the end of exposure.The insulin secretion results showed that, three sweetener groups’ mice insulin secretion showed first increased then decreased with the sweetness increased. The fasting insulin levels of sweet exposed mice were also increased compared to control mice.(4) Chronic sweet exposure changed incretin secretion and intestinal sweet taste sensory systemCompared to the control mice, the long-term exposure of high-sweetness artificial sweeteners were shown to change the release of GLP-1and GIP, because of the short half-life, blood collection tedious process, repeat the measurement process is necessary. At the same time, it also reshape intestinal and oral morphology, up-regulate the expression levels of the sweet receptors (T1R2and T1R3) and glucose transporters (SGLT-1and GLUT-2).In summary, Sweet chronic exposure reshaped the intestinal sensory systems to increase the intestinal absorption rate of glucose in the intestine, promoted incretin secretion to adjuste the blood glucose level by the way indirectly on the release of insulin, These two aspects were associated with the excitation of the intestinal sweet taste receptors. Therefore, we concluded that artificial sweeteners triggered a series of ways to interfere the physiological effects of mice on glucose homeostasis through the effective on the expression of intestinal sweet receptors, affected the energy metabolism balance. These conclusions may shed light on the safe use of artificial sweeteners, and also provide theoretical basis and research programs for the treatment of obesity, diabetes and other metabolic diseases.