Starr, A. | Search bioRxiv

bioRxiv2022

Metabolic Implications of Birth via Cesarean Section in Prairie Vole (Microtus ochrogaster)

Throughout the United States the rates of performed cesarean section (CS) have increased. The scientific community has observed an association between birth by cesarean and the offsprings increased weight at maturity (Masukume, 2019). Studies are being conducted to better understand the relationship between cesarean delivery and offspring metabolism (Kozhimannil, 2013; Kenkel, 2020). To test this potential connection, a diet intervention study has been used to test vaginal delivery (VD) vs CS birth subjects weight gain using a prairie vole model. Vole diets were either supplemented with a high-fat alternative mixed chow (MC) or fed standard vole chow (VC) to induce weight gain. Through this study, we collected sucrose preference, home cage, food consumption data from both birth mode groups and diet conditions. At sacrifice, we collected measures of weight, length, and adipose tissue to analyze for post-mortem body composition in adulthood of each group. CS voles gained more weight than VD voles, despite having lower food consumption and greater locomotive activity. Body composition analysis found that CS animals were longer and heavier than their VD counterparts. Additionally, CS animals were found to have a larger percent brown adipose tissue relative to body weight compared to VD counterparts. Future studies will target the variables contributing to this weight gain among CS offspring by examining factors like muscle mass, and total adiposity through advanced imaging data. Future studies will incorporate exogenous oxytocin administration to examine the impact of birth mode on body weight, metabolism, adiposity, and later life development to determine the possible mechanisms impacting the metabolic outcomes seen in this study.

physiology↗

bioRxiv2019

Glycolysis upregulation is neuroprotective as a compensatory mechanism in ALS

Amyotrophic Lateral Sclerosis (ALS), is a fatal neurodegenerative disorder, with TDP-43 inclusions as a major pathological hallmark. Using a Drosophila model of TDP-43 proteinopathy we found significant alterations in glucose metabolism including increased pyruvate, suggesting that modulating glycolysis may be neuroprotective. Indeed, a high sugar diet improves locomotor and lifespan defects caused by TDP-43 proteinopathy in motor neurons or glia, but not muscle, suggesting that metabolic dysregulation occurs in the nervous system. Overexpressing human glucose transporter GLUT-3 in motor neurons mitigates TDP-43 dependent defects in synaptic vesicle recycling and improves locomotion. Furthermore, PFK mRNA, a key indicator of glycolysis, is upregulated in flies and patient derived iPSC motor neurons with TDP-43 pathology. Surprisingly, PFK overexpression rescues TDP-43 induced locomotor deficits. These findings from multiple ALS models show that mechanistically, glycolysis is upregulated in degenerating motor neurons as a compensatory mechanism and suggest that increased glucose availability is protective.

neuroscience↗