Aspartame consumption is implicated in the development of obesity and metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, 12% kcal fat) or high fat (HF, 60% kcal fat) and further into ad libitum water control (W) or low-dose aspartame (A, 5–7 mg/kg/d in drinking water) treatments for 8 week (n = 10–12 animals/treatment). Animals on aspartame consumed fewer calories, gained less weight and had a more favorable body composition when challenged with HF compared to animals consuming water. Despite this, aspartame elevated fasting glucose levels and an insulin tolerance test showed aspartame to impair insulin-stimulated glucose disposal in both CH and HF, independently of body composition. Fecal analysis of gut bacterial composition showed aspartame to increase total bacteria, the abundance of Enterobacteriaceae and Clostridium leptum. An interaction between HF and aspartame was also observed for Roseburia ssp wherein HF-A was higher than HF-W (P<0.05). Within HF, aspartame attenuated the typical HF-induced increase in the Firmicutes:Bacteroidetes ratio. Serum metabolomics analysis revealed aspartame to be rapidly metabolized and to be associated with elevations in the short chain fatty acid propionate, a bacterial end product and highly gluconeogenic substrate, potentially explaining its negative affects on insulin tolerance. How aspartame influences gut microbial composition and the implications of these changes on the development of metabolic disease require further investigation.

The purpose of the present investigation was to explore the effects of exercise and adrenaline on the mRNA expression of PGC-1α, a master regulator of mitochondrial biogenesis, in rat abdominal adipose tissue. We hypothesized that (1) exercise training would increase PGC-1α mRNA expression in association with increases in mitochondrial marker enzymes, (2) adrenaline would increase PGC-1α mRNA expression and (3) the effect of exercise on PGC-1α mRNA expression in white adipose tissue would be attenuated by a β-blocker. Two hours of daily swim training for 4 weeks led to increases in mitochondrial marker proteins and PGC-1α mRNA expression in epididymal and retroperitoneal fat depots. Additionally, a single 2 h bout of exercise led to increases in PGC-1α mRNA expression immediately following exercise cessation. Adrenaline treatment of adipose tissue organ cultures led to dose-dependent increases in PGC-1α mRNA expression. A supra-physiological concentration of adrenaline increased PGC-1α mRNA expression in epididymal but not retroperitoneal adipose tissue. β-Blockade attenuated the effects of an acute bout of exercise on PGC-1α mRNA expression in epididymal but not retroperitoneal fat pads. In summary, this is the first investigation to demonstrate that exercise training, an acute bout of exercise and adrenaline all increase PGC-1α mRNA expression in rat white adipose tissue. Furthermore it would appear that increases in circulating catecholamine levels may be one potential mechanism mediating exercise induced increases in PGC-1α mRNA expression in rat abdominal adipose tissue.

BackgroundGastrointestinal dysfunction and gut microbial composition disturbances have been widely reported in autism spectrum disorder (ASD). This study examines whether gut microbiome disturbances are present in the BTBRT + tf/j (BTBR) mouse model of ASD and if the ketogenic diet, a diet previously shown to elicit therapeutic benefit in this mouse model, is capable of altering the profile.FindingsJuvenile male C57BL/6 (B6) and BTBR mice were fed a standard chow (CH, 13 % kcal fat) or ketogenic diet (KD, 75 % kcal fat) for 10–14 days. Following diets, fecal and cecal samples were collected for analysis. Main findings are as follows: (1) gut microbiota compositions of cecal and fecal samples were altered in BTBR compared to control mice, indicating that this model may be of utility in understanding gut-brain interactions in ASD; (2) KD consumption caused an anti-microbial-like effect by significantly decreasing total host bacterial abundance in cecal and fecal matter; (3) specific to BTBR animals, the KD counteracted the common ASD phenotype of a low Firmicutes to Bacteroidetes ratio in both sample types; and (4) the KD reversed elevated Akkermansia muciniphila content in the cecal and fecal matter of BTBR animals.ConclusionsResults indicate that consumption of a KD likely triggers reductions in total gut microbial counts and compositional remodeling in the BTBR mouse. These findings may explain, in part, the ability of a KD to mitigate some of the neurological symptoms associated with ASD in an animal model.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-016-0099-3) contains supplementary material, which is available to authorized users.

Maternal obesity and overnutrition during pregnancy and lactation can program an increased risk of obesity in offspring. In this context, improving maternal metabolism may help reduce the intergenerational transmission of obesity. Here we show that, in Sprague-Dawley rats, selectively altering obese maternal gut microbial composition with prebiotic treatment reduces maternal energy intake, decreases gestational weight gain, and prevents increased adiposity in dams and their offspring. Maternal serum metabolomics analysis, along with satiety hormone and gut microbiota analysis, identified maternal metabolic signatures that could be implicated in programming offspring obesity risk and highlighted the potential influence of maternal gut microbiota on maternal and offspring metabolism. In particular, the metabolomic signature of insulin resistance in obese rats normalized when dams consumed the prebiotic. In summary, prebiotic intake during pregnancy and lactation improves maternal metabolism in diet-induced obese rats in a manner that attenuates the detrimental nutritional programming of offspring associated with maternal obesity. Overall, these findings contribute to our understanding of the maternal mechanisms influencing the developmental programming of offspring obesity and provide compelling pre-clinical evidence for a potential strategy to improve maternal and offspring metabolic outcomes in human pregnancy.

Cecal microbiota from type 2 diabetic (db/db) and control (db/(+)) mice was obtained following 6 weeks of sedentary or exercise activity. qPCR analysis revealed a main effect of exercise, with greater abundance of select Firmicutes species and lower Bacteroides/Prevotella spp. in both normal and diabetic exercised mice compared with sedentary counterparts. Conversely, Bifidobacterium spp. was greater in exercised normal but not diabetic mice (exercise × diabetes interaction). How exercise influences gut microbiota requires further investigation.

Objective: Prebiotics and probiotics may be able to modify an obesity-associated gut microbiota. The aim of this study was to examine the individual and combined effects of the prebiotic oligofructose (OFS) and the probiotic Bifidobacterium animalis subsp. lactis BB-12 (BB-12) on gut microbiota and host metabolism in obese rats. Methods: Adult male, diet-induced obese Sprague Dawley rats were randomized to: (1) Control (C); (2) 10% OFS; (3) BB-12; (4) OFS 1 BB-12 for 8 weeks (n 5 9-10 rats/group). Body composition, glycemia, gut permeability, satiety hormones, cytokines, and gut microbiota were examined. Results: Prebiotic, but not probiotic reduced energy intake, weight gain, and fat mass (P < 0.01). OFS, BB-12, and the combined OFS 1 BB-12 improved glycemia (P < 0.05). Individually, OFS and BB-12 reduced insulin levels (P < 0.05). Portal GLP-1 was increased with OFS, whereas probiotic increased GLP-2 (P < 0.05). There was a marked increase in bifidobacteria and lactobacilli (P < 0.01) with OFS that was not observed with probiotic alone. Conclusions: The impact of prebiotic intake on body composition and gut microbiota was of greater magnitude than the probiotic BB-12. Despite this, an improvement in glucose AUC with both prebiotic or probiotic demonstrates the beneficial role of each of these "biotic" agents in glycemic control.

Obesity, and associated metabolic syndrome, have been identified as primary risk factors for the development of knee osteoarthritis (OA), representing nearly 60% of the OA patient population. In this study, we sought to determine the effects of prebiotic fibre supplementation, aerobic exercise, and the combination of the two interventions, on the development of metabolic knee osteoarthritis in a high-fat/high-sucrose (HFS) diet-induced rat model of obesity. Twelve-week-old male Sprague-Dawley rats were randomized into five groups: a non-exercising control group fed a standard chow diet, a non-exercising group fed a HFS diet, a non-exercising group fed a HFS diet combined with prebiotic fibre supplement, an exercise group fed a HFS diet, and an exercise group fed a HFS diet combined with prebiotic fibre supplement. Outcome measures included knee joint damage, percent body fat, insulin sensitivity, serum lipid profile, serum endotoxin, serum and synovial fluid cytokines and adipokines, and cecal microbiota. Prebiotic fibre supplementation, aerobic exercise, and the combination of the two interventions completely prevented knee joint damage that is otherwise observed in this rat model of obesity. Prevention of knee damage was associated with a normalization of insulin resistance, leptin levels, dyslipidemia, gut microbiota, and endotoxemia in the HFS-fed rats.

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