leptin and trichlorosucrose

The effect of nonnutritive sweeteners on appetite is controversial. Some studies have found changes in certain appetite control hormones with sucralose intake that may be through interaction with sweet taste receptors located in the intestine.. The aim of this study was to evaluate whether sucralose consumption could produce changes in fasting plasma concentrations of appetite-regulating hormones, including glucagon-like peptide 1, ghrelin, peptide tyrosine tyrosine, and leptin, and secondarily in insulin resistance.. A 2-week parallel randomized clinical trial with an additional visit conducted 1 week after dosing termination.. Sixty healthy, normal-weight individuals, without habitual consumption of nonnutritive sweeteners were recruited from July 2015 to March 2017 in Mexico City.. Daily sucralose consumption at 15% of the acceptable daily intake by using commercial sachets added to food. The control group followed the same protocol without an intervention.. Fasting concentrations of appetite regulating hormones before and after the intervention. Fasting glucose and insulin concentrations were measured to assess insulin resistance as a secondary outcome.. Basal and final concentrations were compared using Wilcoxon matched-pairs test and Mann-Whitney U test for analysis between groups. Repeated measures analysis of variance was used to evaluate changes in the homeostasis model assessment of insulin resistance.. Sucralose was not associated with changes in any of the hormones measured. One week postintervention, an incremental change (P=0.04) in the homeostasis model assessment of insulin resistance was found in the intervention group.. Sucralose intake is not associated with changes in fasting concentrations of glucagon-like peptide 1, ghrelin, peptide tyrosine tyrosine, or leptin. An increase in the homeostasis model assessment of insulin resistance observed only at 1 week postdosing is of unknown clinical significance, if any.

Topics: Adult; Appetite; Blood Glucose; Diet; Dipeptides; Fasting; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Insulin Resistance; Leptin; Male; Mexico; Sucrose

Dietary guidelines for obesity typically focus on three food groups (carbohydrates, fat, and protein) and caloric restriction. Intake of noncaloric nutrients, such as salt, are rarely discussed. However, recently high salt intake has been reported to predict the development of obesity and insulin resistance. The mechanism for this effect is unknown. Here we show that high intake of salt activates the aldose reductase-fructokinase pathway in the liver and hypothalamus, leading to endogenous fructose production with the development of leptin resistance and hyperphagia that cause obesity, insulin resistance, and fatty liver. A high-salt diet was also found to predict the development of diabetes and nonalcoholic fatty liver disease in a healthy population. These studies provide insights into the pathogenesis of obesity and diabetes and raise the potential for reduction in salt intake as an additional interventional approach for reducing the risk for developing obesity and metabolic syndrome.

Topics: Adult; Aged; Aged, 80 and over; Animals; Diabetes Mellitus; Fructokinases; Fructose; Humans; Leptin; Metabolic Syndrome; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Non-alcoholic Fatty Liver Disease; Obesity; Sodium Chloride, Dietary; Sucrose; Transcription Factors

We developed an assay for quantifying the reward value of nutrient and used it to analyze the effects of metabolic state and leptin. In this assay, mice chose between two sippers, one of which dispensed water and was coupled to optogenetic activation of dopaminergic (DA) neurons and the other of which dispensed natural or artificial sweeteners. This assay measured the reward value of sweeteners relative to lick-induced optogenetic activation of DA neurons. Mice preferred optogenetic stimulation of DA neurons to sucralose, but not to sucrose. However, the mice preferred sucralose plus optogenetic stimulation versus sucrose. We found that food restriction increased the value of sucrose relative to sucralose plus optogenetic stimulation, and that leptin decreased it. Our data suggest that leptin suppresses the ability of sucrose to drive taste-independent DA neuronal activation and provide new insights into the mechanism of leptin's effects on food intake.

Topics: Analysis of Variance; Animals; Channelrhodopsins; Choice Behavior; Dopamine Plasma Membrane Transport Proteins; Dose-Response Relationship, Drug; Drinking Behavior; Fasting; Food; Food Preferences; Gene Expression Regulation; Image Processing, Computer-Assisted; Lasers; Leptin; Luminescent Proteins; Magnetic Resonance Imaging; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Oxygen; Proteins; Proto-Oncogene Proteins c-fos; Reward; RNA, Untranslated; Sucrose; Sweetening Agents; Tyrosine 3-Monooxygenase; Ventral Tegmental Area