Currently, there is a significant percentage of the population who are or will be classified as obese, necessitating novel strategies to facilitate sustainable weight loss. Reductions in basal metabolic rate occur in the face of weight loss, and pose formidable barriers to individuals attempting to sustain meaningful weight reductions. This grand rounds discusses the mechanisms by which non-shivering thermogenesis may provide insight into metabolic pathways that can become druggable targets to facilitate sustainable weight loss. Specifically highlighted is fact that non-shivering thermogenesis results in activation and expansion of brown and beige adipose tissues as well as activates pathways in skeletal muscle which increase metabolic flux and activity of muscle fibers through futile calcium cycling across the endoplasmic reticulum all facilitating an increase in metabolism. Finally, the protocol highlights the fact there are sexual dimorphisms with respect to these metabolic processes in keeping with the National Institutes of Health mandate of treating sex as a biologic variable.

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