leptin and fagomine

This study examines the long-term functional effects of d-fagomine on sucrose-induced factors of metabolic dysfunctions and explores possible molecular mechanisms behind its action.. Wistar Kyoto rats are fed a 35% sucrose solution with d-fagomine (or not, for comparison) or mineral water (controls) for 24 weeks. The following are recorded: body weight; energy intake; glucose tolerance; plasma leptin concentration and lipid profile; populations of Bacteroidetes, Firmicutes, bacteroidales, clostridiales, enterobacteriales, and Escherichia coli in feces; blood pressure; urine uric acid and F. d-fagomine counteracts sucrose-induced steatosis and hypertension, presumably by reducing the postprandial levels of fructose in the liver.

Topics: Adipose Tissue; Animals; Diglycerides; Energy Intake; Fagopyrum; Gastrointestinal Microbiome; Hypertension; Imino Pyranoses; Isoprostanes; Leptin; Lipids; Liver; Male; Non-alcoholic Fatty Liver Disease; Postprandial Period; Rats, Inbred WKY; Sucrose; Uric Acid

Food contains bioactive compounds that may prevent changes in gut microbiota associated with Westernized diets. The aim of this study is to explore the possible additive effects of D-fagomine and ω-3 PUFAs (EPA/DHA 1:1) on gut microbiota and related risk factors during early stages in the development of fat-induced pre-diabetes. Male Sprague Dawley (SD) rats were fed a standard diet, or a high-fat (HF) diet supplemented with D-fagomine, EPA/DHA 1:1, a combination of both, or neither, for 24 weeks. The variables measured were fasting glucose and glucose tolerance, plasma insulin, liver inflammation, fecal/cecal gut bacterial subgroups and short-chain fatty acids (SCFAs). The animals supplemented with D-fagomine alone and in combination with ω-3 PUFAs accumulated less fat than those in the non-supplemented HF group and those given only ω-3 PUFAs. The combined supplements attenuated the high-fat-induced incipient insulin resistance (IR), and liver inflammation, while increasing the cecal content, the Bacteroidetes:Firmicutes ratio and the populations of Bifidobacteriales. The functional effects of the combination of D-fagomine and EPA/DHA 1:1 against gut dysbiosis and the very early metabolic alterations induced by a high-fat diet are mainly those of D-fagomine complemented by the anti-inflammatory action of ω-3 PUFAs.

Topics: Animals; Blood Glucose; Diet, High-Fat; Drug Therapy, Combination; Fatty Acids, Omega-3; Gastrointestinal Microbiome; Glucose Tolerance Test; Imino Pyranoses; Insulin; Leptin; Male; Prediabetic State; Rats; Rats, Sprague-Dawley; Risk Factors

d-Fagomine is a natural iminosugar that counteracts the short-term effects of a high-energy-dense diet on body weight, fasting blood glucose levels and the proportion of gut Enterobacteriales. This suggests that supplementation with d-fagomine for longer periods may delay the onset of other factors related to metabolic syndrome. Here we evaluate the effects of d-fagomine dietary supplementation on relevant metabolic hormones and lipid peroxidation. Adult Sprague-Dawley rats were fed a high-fat high-sucrose diet supplemented or not with d-fagomine (0.065% w/w) for 9 weeks. Weight gain, plasma triglycerides, glucose, insulin, glucagon, ghrelin, leptin, and urine F2-isoprostanes were evaluated. d-Fagomine attenuated the changes induced by the high-energy-dense diet in triglycerides and all the hormones tested. These results suggest that d-fagomine may help to avert the complications associated with unhealthy eating by counteracting the effects of high-energy-dense diets during the early stages of the development of metabolic disorders.

Topics: Animals; Blood Glucose; Body Weight; Diet, High-Fat; Humans; Imino Pyranoses; Insulin; Leptin; Male; Obesity; Rats; Rats, Sprague-Dawley; Triglycerides