Low Doses of Sucralose Alter Fecal Microbiota in High-Fat Diet-Induced Obese Rats

Artificial sweeteners (AS) have been widely used as sugar substitutes to reduce calorie intake. However, it was reported that high doses of AS induced glucose intolerance via modulating gut microbiota. The objective of this study was to investigate the effects of lower doses of sucralose on fecal microbiota in obesity. Eight weeks after high-fat diet (HFD), the male Sprague Dawley rats were randomly divided into four groups (6 in each group) and administrated by a daily gavage of 2 ml normal saline (CON), 0.54 mM sucralose (N054), 0.78 mM sucralose (N078), and 324 mM sucrose (S324), respectively. After 4 weeks, fecal samples were obtained and analyzed by 16S ribosomal RNA gene sequencing. The richness and diversity of fecal microbiota were not changed by sucralose or sucrose. Both 0.54 mM (0.43 mg) and 0.78 mM (0.62 mg) sucralose tended to reduce the beneficial bacteria, Lactobacillaceae and Akkermansiaceae. The relative abundance of family Acidaminoccaceae and its genus Phascolarctobacteriam were increased after 0.54 mM sucralose. In functional prediction, 0.54 mM sucralose increased profiles of carbohydrate metabolism, whereas 0.78 mM sucralose enhanced those of amino acid metabolism. The lower doses of sucralose might alter the compositions of fecal microbiota. The effects of sucralose in different dosages should be considered in the future study.

Adrenalectomy improves glycemic responses in congenic obese LA/Ntul//-cp RATS

To determine the effects of adrenalectomy on typical insulin-mediated glycemic responses in male obese rats, groups (n=6 -12 rats/phenotype) of normally reared congenic lean and obese animals were fed a Purina chow diet from 6 to 9 weeks of age, and the Chow diet plus a highly palatable cafeteria diet from 9 to 12 weeks of age. The congenic LA/Ntul//-cp rat strain is noted for its longevity and early expression of the obese trait but remains non-diabetic throughout much if not all of its normal lifespan. Subgroups of obese animals were subjected to bilateral adrenalectomy (ADX) at 6 weeks of age to remove glucocorticoid contributions to glycemic parameters. Measures of weight gain (WG )and of glucose tolerance (OGT) were obtained in the three treatment groups at 6, 9 and 12 weeks of age. WG on ADX-obese rats was similar to that of their lean littermates at 6 and 9 weeks of age on the chow diet but increased to twice that observed in their lean littermates from 9 to 12 weeks of age. OGT responses after 30 to 60 minutes and the area under the OGT curve were impaired but not diabetic in obese animals at all ages compared to lean littermates and returned toward those of normally lean rats after ADX. The Insulin to glucose ratio (I:G) was also consistent with insulin resistance in obese but not in ADX-obese or lean rats at 12 weeks of age. In conclusion, ADX resulted in normalization of OGT and glycemic parameters in the obese phenotype at 9 and 12 weeks of age. These results are consistent with normalization of typical insulin-mediated components of glycemic parameters and glucose uptake in peripheral tissues following adrenalectomy of congenic obese rats. The results further suggest that the counterregulatory effects of insulin and glucocorticoid hormones may be contributory to the impaired glycemic responses in the obese phenotype of the LA/N//-cp (corpulent) rat and are consistent with a receptor-mediated element in the development of insulin resistance and glucose uptake in peripheral tissues commonly associated with the early development of obesity in this strain.

Behavioral and Metabolic Effects of a Calorie-Restricted Cafeteria Diet and Oleuropein Supplementation in Obese Male Rats

Diet-induced obesity models are widely used to investigate dietary interventions for treating obesity. This study was aimed to test whether a dietary intervention based on a calorie-restricted cafeteria diet (CAF-R) and a polyphenolic compound (Oleuropein, OLE) supplementation modified sucrose intake, preference, and taste reactivity in cafeteria diet (CAF)-induced obese rats. CAF diet consists of high-energy, highly palatable human foods. Male rats fed standard chow (STD) or CAF diet were compared with obese rats fed CAF-R diet, alone or supplemented with an olive tree leaves extract (25 mg/kg*day) containing a 20.1% of OLE (CAF-RO). Biometric, food consumption, and serum parameters were measured. CAF diet increased body weight, food and energy consumption and obesity-associated metabolic parameters. CAF-R and CAF-RO diets significantly attenuated body weight gain and BMI, diminished food and energy intake and improved biochemical parameters such as triacylglycerides and insulin resistance which did not differ between CAF-RO and STD groups. The three cafeteria groups diminished sucrose intake and preference compared to STD group. CAF-RO also diminished the hedonic responses for the high sucrose concentrations compared with the other groups. These results indicate that CAF-R diet may be an efficient strategy to restore obesity-associated alterations, whilst OLE supplementation seems to have an additional beneficial effect on sweet taste function.

Lycium Barbarum Polysaccharides Regulate the Gut Microbiota To Modulate Metabolites in High Fat Diet-Induced Obese Rats

Previous studies had indicated that the gut microbiota was a main internal factor leading to obesity through energy storage and metabolic disorders. Lycium Barbarum Polysaccharides (LBP) have been discovered with a more protective effect on intestinal flora. But it is unclear whether LBP could regulate the gut microbiota to modulate metabolites, finally relieving obesity. A related study of high-throughput 16S rRNA sequencing and serum metabolomics profiling in LBP intervention on high fat diet-induced obese rats then explored the beneficial effects of LBP and the underlying mechanism. LBP affected lipid parameters such as total cholesterol, Triglyceride, and High-density lipoprotein. The gut microbiota result detected 16 types of the phylum of bacteria in total, while four of them (Bacteroidetes, Firmicutes, Proteobacteria, Deferribacteres) were significantly different. LBP upregulated the level of Firmicutes of obese rats. LBP might associate with the gut microbiota that participates in the membrane transport and metabolism of amino acid, carbohydrate, energy, and lipid. The serum metabolomics profiling of high-fat diet-induced obesity rats found over 30 differential metabolites between model and intervention groups. Primary metabolites include cortisol, glycohyocholic acid, homo-L-arginine, ursodeoxycholic acid, isoursodeoxycholic acid, glycoursocholic acid, 4-ethylphenylsulfate, deoxycholic acid, 7-hydroxy-3-oxocholanoic acid isomers, gly-phe, pipecolic acid, proline betaine, and pyrocatechol sulfate. Pathway analysis in serum found four disorder pathways: glycerophospholipid metabolism, glycine-serine-threonine metabolism, biosynthesis of unsaturated fatty acids, and linoleic acid metabolism. The studies revealed that LBP treatment increased the diversity of fecal microorganisms and reduced metabolic disorders in obese rats. LBP ameliorated metabolic disorders and rebalanced the gut microbiome.