The brain has evolved an internal model of gravity to cope with life in the Earth's gravitational environment. How this internal model benefits the implementation of skilled movement has remained unsolved. One prevailing theory has assumed that this internal model is used to compensate for gravity's mechanical effects on the body, such as to maintain invariant motor trajectories. Alternatively, gravity force could be used purposely and efficiently for the planning and execution of voluntary movements, thereby resulting in direction-depending kinematics. Here we experimentally interrogate these two hypotheses by measuring arm kinematics while varying movement direction in normal and zero-G gravity conditions. By comparing experimental results with model predictions, we show that the brain uses the internal model to implement control policies that take advantage of gravity to minimize movement effort.
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: Informed consent, and consent to publish, was obtained from all participants. The regional ethics committee of Burgundy (C.E.R) and the ethics committee of INSERM (Institut National de la Santé et de la Recherche Médicale) approved experimental protocols. All procedures were carried out in agreement with local requirements and international norms (Declaration of Helsinki, 1964).
© 2016, Gaveau et al.
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Obesity is a major risk factor for type 2 diabetes, dyslipidemia, cardiovascular disease, and hypertension. Intriguingly, there is a subset of metabolically healthy obese (MHO) individuals who are seemingly able to maintain a healthy metabolic profile free of metabolic syndrome. The molecular underpinnings of MHO, however, are not well understood. Here, we report that CTRP10/C1QL2-deficient mice represent a unique female model of MHO. CTRP10 modulates weight gain in a striking and sexually dimorphic manner. Female, but not male, mice lacking CTRP10 develop obesity with age on a low-fat diet while maintaining an otherwise healthy metabolic profile. When fed an obesogenic diet, female Ctrp10 knockout (KO) mice show rapid weight gain. Despite pronounced obesity, Ctrp10 KO female mice do not develop steatosis, dyslipidemia, glucose intolerance, insulin resistance, oxidative stress, or low-grade inflammation. Obesity is largely uncoupled from metabolic dysregulation in female KO mice. Multi-tissue transcriptomic analyses highlighted gene expression changes and pathways associated with insulin-sensitive obesity. Transcriptional correlation of the differentially expressed gene (DEG) orthologs in humans also shows sex differences in gene connectivity within and across metabolic tissues, underscoring the conserved sex-dependent function of CTRP10. Collectively, our findings suggest that CTRP10 negatively regulates body weight in females, and that loss of CTRP10 results in benign obesity with largely preserved insulin sensitivity and metabolic health. This female MHO mouse model is valuable for understanding sex-biased mechanisms that uncouple obesity from metabolic dysfunction.
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