Short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, are metabolites formed by gut microbiota from complex dietary carbohydrates. Butyrate and acetate were reported to protect against diet-induced obesity without causing hypophagia, while propionate was shown to reduce food intake. However, the underlying mechanisms for these effects are unclear. It was suggested that SCFAs may regulate gut hormones via their endogenous receptors Free fatty acid receptors 2 (FFAR2) and 3 (FFAR3), but direct evidence is lacking. We examined the effects of SCFA administration in mice, and show that butyrate, propionate, and acetate all protected against diet-induced obesity and insulin resistance. Butyrate and propionate, but not acetate, induce gut hormones and reduce food intake. As FFAR3 is the common receptor activated by butyrate and propionate, we examined these effects in FFAR3-deficient mice. The effects of butyrate and propionate on body weight and food intake are independent of FFAR3. In addition, FFAR3 plays a minor role in butyrate stimulation of Glucagon-like peptide-1, and is not required for butyrate- and propionate-dependent induction of Glucose-dependent insulinotropic peptide. Finally, FFAR3-deficient mice show normal body weight and glucose homeostasis. Stimulation of gut hormones and food intake inhibition by butyrate and propionate may represent a novel mechanism by which gut microbiota regulates host metabolism. These effects are largely intact in FFAR3-deficient mice, indicating additional mediators are required for these beneficial effects.

To assess safety and mobility outcomes utilizing the Indego powered exoskeleton in indoor and outdoor walking conditions with individuals previously diagnosed with a spinal cord injury (SCI). We conducted a multicenter prospective observational cohort study in outpatient clinics associated with 5 rehabilitation hospitals. A convenience sample of nonambulatory individuals with SCI ( = 32) completed an 8-week training protocol consisting of walking training 3 times per week utilizing the Indego powered exoskeleton in indoor and outdoor conditions. Participants were also trained in donning/doffing the exoskeleton during each session. Safety measures such as adverse events (AEs) were monitored and reported. Time and independence with donning/doffing the exoskeleton as well as walking outcomes to include the 10-meter walk test (10MWT), 6-minute walk test (6MWT), Timed Up & Go test (TUG), and 600-meter walk test were evaluated from midpoint to final evaluations. All 32 participants completed the training protocol with limited device-related AEs, which resulted in no interruption in training. The majority of participants in this trial were able to don and doff the Indego independently. Final walking speed ranged from 0.19 to 0.55 m/s. Final average indoor and outdoor walking speeds among all participants were 0.37 m/s ( = 0.08, 0.09, respectively), after 8 weeks of training. Significant ( < .05) improvements were noted between midpoint and final gait speeds in both indoor and outdoor conditions. Average walking endurance also improved among participants after training. The Indego was shown to be safe for providing upright mobility to 32 individuals with SCIs who were nonambulatory. Improvements in speed and independence were noted with walking in indoor and outdoor conditions as well as with donning/doffing the exoskeleton.

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