Studies suggest the gut microbiota contributes to the development of obesity and metabolic syndrome. Exercise alters microbiota composition and diversity and is protective of these maladies. We tested whether the protective metabolic effects of exercise are mediated through fecal components through assessment of body composition and metabolism in recipients of fecal microbiota transplantation (FMT) from exercise-trained (ET) mice fed normal or high-energy diets. Donor C57BL/6J mice were fed a chow or high-fat, high-sucrose diet (HFHS) for 4 wk to induce obesity and glucose intolerance. Mice were divided into sedentary (Sed) or ET groups (6 wk treadmill-based ET) while maintaining their diets, resulting in four donor groups: chow sedentary (NC-Sed) or ET (NC-ET) and HFHS sedentary (HFHS-Sed) or ET (HFHS-ET). Chow-fed recipient mice were gavaged with feces from the respective donor groups weekly, creating four groups (NC-Sed-R, NC-ET-R, HFHS-Sed-R, HFHS-ET-R), and body composition and metabolism were assessed. The HFHS diet led to glucose intolerance and obesity in the donors, whereas exercise training (ET) restrained adiposity and improved glucose tolerance. No donor group FMT altered recipient body composition. Despite unaltered adiposity, glucose levels were disrupted when challenged in mice receiving feces from HFHS-fed donors, irrespective of donor-ET status, with a decrease in insulin-stimulated glucose clearance into white adipose tissue and large intestine and specific changes in the recipient’s microbiota composition observed. FMT can transmit HFHS-induced disrupted glucose metabolism to recipient mice independently of any change in adiposity. However, the protective metabolic effect of ET on glucose metabolism is not mediated through fecal factors.

Insulin‐like Growth Factor‐1 (IGF‐1) has been studied extensively for its ability to promote neuronal growth and excitability. Declining levels of IGF‐1 have been correlated with impaired learning and memory as well as an increased risk of neurodegenerative diseases. While neuronal regulation by IGF‐1 is well understood, the role of IGF‐1 in influencing astrocyte function requires further exploration. Astrocytes regulate many aspects of the brain microenvironment, including controlling glutamate‐glutamine cycling, which ultimately supports neuronal metabolism, neurotransmission, and protection from over stimulation. In this study, we examined whether IGF‐1 acts through its cognate receptor, IGFR, to alter astrocytic glutamate handling. We utilized both small molecule IGFR inhibitors and Cre‐driven genetic approaches to reduce IGFR in vivo and in cultured rodent astrocytes. When IGFR was knocked out of primary astrocytes derived from igfrf/f mice using AAV5‐CMV‐Cre, significant reductions in glutamate uptake were observed. Similarly, inhibition of IGFR with picropodophyllotoxin for 2 h, as well as 24 h, reduced glutamate uptake in vitro. Mechanistically, short‐term inhibition of IGFR resulted in a significant decrease in glutamate transporter availability on the cell surface, as assessed by biotinylation. Long‐term inhibition of IGFR led to significant reductions in mRNA expression of glutamate transport machinery, as assessed with qPCR. Reduced glutamate transporter mRNA was also observed in the brains of astrocyte‐specific IGFR‐deficient mice, three to four months after knock‐out was induced with tamoxifen. Interestingly, long‐term IGF‐1 inhibition also resulted in an increase in adenosine triphosphate‐stimulated glutamate release, though no change in adenosine triphosphate‐stimulated calcium flux was observed nor were any changes in purinergic receptor protein expression. Together, these data suggest that reduced IGF‐1 signaling will favor an accumulation of extrasynaptic glutamate, which may contribute to neurodegeneration in disease states where IGF‐1 levels are low. Cover Image for this issue: doi: .

At the levels of Hsp72 over-expression reported herein, skeletal muscle-specific Hsp72 overexpression via IM injection has the capacity to increase insulin-stimulated glucose clearance in this muscle. However, upon systemic injection, which results in lower muscle Hsp72 overexpression, no beneficial effects on whole-body metabolism are observed.