RESUMO
The objective of the study was to investigate the preventive effect on obesity-related conditions of rosemary (Rosmarinus officinalis L.) extract (RE) in young, healthy rats fed a high-fat Western-style diet to complement the existing knowledge gap concerning the anti-obesity effects of RE in vivo. Sprague Dawley rats (71.3 ± 0.46 g) were fed a high-fat Western-style diet (WD) or WD containing either 1 g/kg feed or 4 g/kg feed RE for six weeks. A group fed standard chow served as a negative control. The treatments did not affect body weight; however, the liver fat percentage was reduced in rats fed RE, and NMR analyses of liver tissue indicated that total cholesterol and triglycerides in the liver were reduced. In plasma, HDL cholesterol was increased while triglycerides were decreased. Rats fed high RE had significantly increased fasting plasma concentrations of Glucagon-like peptide-1 (GLP-1). Proteomics analyses of liver tissue showed that RE increased enzymes involved in fatty acid oxidation, possibly associated with the higher fasting GLP-1 levels, which may explain the improvement of the overall lipid profile and hepatic fat accumulation. Furthermore, high levels of succinic acid in the cecal content of RE-treated animals suggested a modulation of the microbiota composition. In conclusion, our results suggest that RE may alleviate the effects of consuming a high-fat diet through increased GLP-1 secretion and changes in microbiota composition.
RESUMO
CONTEXT: Glucose homeostasis is under circadian control through both endocrine and intracellular mechanisms, with several lines of evidence suggesting that melatonin affects glucose homeostasis. OBJECTIVE: To evaluate the acute in vivo and in situ effects of melatonin on secretion of the incretin hormones, glucagon-like-peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), and their impact on ß-cell insulin secretion. DESIGN: A human randomized, double-blinded, placebo-controlled crossover study combined with a confirmatory in situ study of perfused rat intestines. SETTING: Aarhus University Hospital. METHODS: Fifteen healthy male participants were examined 2â ×â 2 times: an oral glucose tolerance test (OGTT) was performed on day 1 and an isoglycemic IV glucose infusion replicating the blood glucose profile of the OGTT day was performed on day 2. These pairs of study days were repeated on treatment with melatonin and placebo, respectively. For the in situ study, 6 rat intestines and 4 rat pancreases were perfused arterially with perfusion bufferâ ±â melatonin. The intestines were concomitantly perfused with glucose through the luminal compartment. RESULTS: In humans, melatonin treatment resulted in reduced GIP secretion compared with placebo (ANOVA Pâ =â 0.003), an effect also observed in the perfused rat intestines (ANOVA Pâ =â 0.003), in which GLP-1 secretion also was impaired by arterial melatonin infusion (ANOVA Pâ <â 0.001). Despite a decrease in GIP levels, the in vivo glucose-stimulated insulin secretion was unaffected by melatonin (Pâ =â 0.78). CONCLUSION: Melatonin reduced GIP secretion during an oral glucose challenge in healthy young men but did not affect insulin secretion. Reduced GIP secretion was confirmed in an in situ model of the rat intestine.