Schwartze, K. | Search bioRxiv

bioRxiv2024

Aerobic capacity and exercise mediate protection against hepatic steatosis via enhanced bile acid metabolism.

High cardiorespiratory fitness and exercise show evidence of altering bile acid (BA) metabolism and are known to protect or treat diet-induced hepatic steatosis, respectively. Here, we tested the hypothesis that high intrinsic aerobic capacity and exercise both increase hepatic BA synthesis measured by the incorporation of 2H2O. We also leveraged mice with inducible liver-specific deletion of Cyp7a1 (LCyp7a1KO), which encodes the rate-limiting enzyme for BA synthesis, to test if exercise-induced BA synthesis is critical for exercise to reduce hepatic steatosis. The synthesis of hepatic BA, cholesterol, and de novo lipogenesis was measured in rats bred for either high (HCR) vs. low (LCR) aerobic capacity consuming acute and chronic high-fat diets. HCR rats had increased synthesis of cholesterol and certain BA species in the liver compared to LCR rats. We also found that chronic exercise with voluntary wheel running (VWR) (4 weeks) increased newly synthesized BAs of specific species in male C57BL/6J mice compared to sedentary mice. Loss of Cyp7a1 resulted in fewer new BAs and increased liver triglycerides compared to controls after a 10-week high-fat diet. Additionally, exercise via VWR for 4 weeks effectively reduced hepatic triglycerides in the high-fat diet-fed control male and female mice as expected; however, exercise in LCyp7a1KO mice did not lower liver triglycerides in either sex. These results show that aerobic capacity and exercise increase hepatic BA metabolism, which may be critical for combatting hepatic steatosis. HighlightsO_LIRats with intrinsic high aerobic capacity have more significant reductions in de novo lipogenesis and increased cholesterol and bile acid synthesis on a high-fat diet compared to rats with low aerobic capacity. C_LIO_LIChronic exercise increases hepatic bile acid synthesis in mice. C_LIO_LILoss of Cyp7a1 blunts the capacity for exercise to increase bile acid synthesis and treat hepatic steatosis in male and female mice fed a high-fat diet. C_LI

physiology↗

bioRxiv2023

Initial and corrective submovement encoding differences within primary motor cortex during precision reaching

Precision reaching tasks often require corrective submovements for successful completion. Most studies of reaching have focused on single initial movements, and the cortical encoding model was implied to be the same for all submovements. However, corrective submovements may show different encoding patterns from the initial submovement with distinct patterns of activation across the population. Two rhesus macaques performed a precision center-out-task with small targets. Neural activity from single units in primary motor cortex and associated behavioral data were recorded to evaluate movement characteristics. Neural population data and individual neuronal firing rates identified with a peak finding algorithm to identify peaks in hand speed were examined for encoding differences between initial and corrective submovements. Individual neurons were fitted with a regression model that included the reach vector, position, and speed to predict firing rate. For both initial and corrective submovements, the largest effect remained movement direction. We observed a large subset changed their preferred direction greater than 45{degrees} between initial and corrective submovements. Neuronal depth of modulation also showed considerable variation when adjusted for movement speed. By utilizing principal component analysis, neural trajectories of initial and corrective submovements progressed through different neural subspaces. These findings all suggest that different neural encoding patterns exist for initial and corrective submovements within the cortex. We hypothesize that this variation in how neurons change to encode small, corrective submovements might allow for a larger portion of the neural space being used to encode a greater range of movements with varying amplitudes and levels of precision. New and NoteworthyNeuronal recordings matched with kinematic behavior were collected in a precision center-out task that often required corrective movements. We reveal large differences in preferred direction and depth of modulation between initial and corrective submovements across the neural population. We then present a model of the neural population describing how these shifts in tuning create different subspaces for signaling initial and corrective movements likely to improve motor precision.

neuroscience↗