Cell-Specific "Competition for Calories" Drives Asymmetric Nutrient-Energy Partitioning, Obesity, and Metabolic Diseases in Human and Non-human Animals.

The mammalian body is a complex physiologic "ecosystem" in which cells compete for calories (i.e., nutrient-energy). Axiomatically, cell-types with competitive advantages acquire a greater number of consumed calories, and when possible, increase in size and/or number. Thus, it is logical and parsimonious to posit that obesity is the competitive advantages of fat-cells (adipocytes) driving a disproportionate acquisition and storage of nutrient-energy. Accordingly, we introduce two conceptual frameworks. describes the context-dependent, cell-specific that determines the partitioning of nutrient-energy to oxidation, anabolism, and/or storage; and which describes the number of calories available to constrain energy-intake via the inhibition of the sensorimotor appetitive cells in the liver and brain that govern ingestive behaviors. Inherent in these frameworks is the independence and dissociation of the energetic demands of metabolism and the neuro-muscular pathways that initiate ingestive behaviors and energy intake. As we demonstrate, if the sensorimotor cells suffer relative caloric deprivation via asymmetric competition from other cell-types (e.g., skeletal muscle- or fat-cells), energy-intake is increased to compensate for both and merely deficits in energy-homeostasis (i.e., true and false signals, respectively). Thus, we posit that the chronic positive energy balance (i.e., over-nutrition) that leads to obesity and metabolic diseases is engendered by deficits (i.e., driven by the asymmetric inter-cellular and concomitant differential partitioning of nutrient-energy to storage. These frameworks, in concert with our previous theoretic work, the , provide a parsimonious and rigorous explanation for the rapid rise in the global prevalence of increased body and fat mass, and associated metabolic dysfunctions in humans and other mammals inclusive of companion, domesticated, laboratory, and feral animals.