Cannon's initial publications, alongside Stanley Prusiner, definitively showed that thermogenesis was primarily driven by mitochondrial uncoupling, likely induced by the presence of free fatty acids. She subsequently showcased important elements in controlling the immediate function of the uncoupling protein, involving fatty acids, possibly their CoA derivatives, and reactive oxygen species (ROS) products. Her articles on regulating ATP synthase levels in mitochondria relative to electron transport chain density, demonstrated in brown adipose tissue, suggest that this concept applies universally, with the P1 isoform of subunit c governing fully assembled enzyme levels in the membrane.
Cannon pioneered primary cell culture systems that underpin knowledge of brown adipocyte development and recruitment. Using these cultures, she identified adrenergic signal transduction pathways responsible for both acute thermogenesis and chronic actions like cell proliferation and differentiation triggered by noradrenaline. She further clarified that the development paths of brown and white adipocytes are separate, with brown adipocytes showing characteristics of skeletal muscle early in their differentiation process. In her later research, she found that cultured adipocytes from different white adipose depots contained precursor cells capable of adopting a brown-like or "brite" phenotype, also known as beige fat. Although these findings have sparked significant interest, she has advised caution regarding the belief that these cells alone will solve obesity problems.
Focusing on integrative physiology, Cannon's research on mice lacking the UCP1 gene revealed that there are no alternative mechanisms for adrenergically induced adaptive thermogenesis apart from UCP1 in brown adipose tissue. This finding challenges the notion of adaptive adrenergic muscular thermogenesis and suggests that UCP1-deficient mice tend to develop modest obesity spontaneously. Moreover, she advocated for humanizing mice by providing them with appealing diets and maintaining their housing conditions at thermoneutral temperatures to mimic the metabolism of adult humans at its lowest point. Furthermore, her review on active brown adipose tissue in adult humans has prompted numerous follow-up experiments and offered promising avenues for pharmacological interventions in obesity management.