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

Abstract

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. Asymmetric Nutrient-Energy Partitioning describes the context-dependent, cell-specific competition for calories that determines the partitioning of nutrient-energy to oxidation, anabolism, and/or storage; and Effective Caloric Intake 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 real and merely apparent 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 apparent deficits (i.e., false signals) driven by the asymmetric inter-cellular competition for calories and concomitant differential partitioning of nutrient-energy to storage. These frameworks, in concert with our previous theoretic work, the Maternal Resources Hypothesis, 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.

Meat and mental health: a systematic review of meat abstention and depression, anxiety, and related phenomena

“…Nevertheless, a number of the studies failed to include important potential confounders and effect modifiers. These include race, ethnic, or religious affiliation, social norms, as well as lifestyle behaviors that directly affect health (e.g., smoking, and alcohol use) and the physiologic determinants of dietary energy intake (e.g., physical activity, body cellularity; Archer 2018b; Archer, Lavie, and Hill 2018a;Archer et al 2018e). Given that when compared to the general population, individuals who follow a vegetarian diet tend to be more health-conscious, more physically active, more highly educated, consume less alcohol, be nonsmokers and have higher socio-economic status Chang-Claude et al 2005), it is essential for future studies to include detailed information on participants' health and behavioral histories and current characteristics.…”

The Failure to Measure Dietary Intake Engendered a Fictional Discourse on Diet-Disease Relations

“…And more importantly, the effects of dietary intake are entirely dependent on the physiologic context of the consuming individual ( 15 ). Thus, with respect to diet-related health, it is not what is eaten that affects health and disease, but what one's body does with what was eaten ( 113 , 114 ). Therefore, as we previously detailed ( 15 , 55 , 113 ), the idea that “you are what you eat” is demonstrative of prescientific thinking [i.e., magico-religious reasoning ( 55 )], “physiologic illiteracy” ( 15 , 114 ), and flouts centuries of progress in medical science because dietary components cannot have effects independent of the physiologic context of the consuming individual ( 15 , 55 , 113 , 114 ).…”

“…For a review please see ( 15 , 113 ). Finally, research dating to the 1950s demonstrated that the “over-consumption” that leads to obesity and metabolic disease is not driven by dietary factors per se , but by physical inactivity-induced increments in energy intake ( 113 , 114 , 131 – 134 ) and non-genetic evolutionary processes (i.e., accumulative maternal effects) ( 113 , 114 , 135 – 137 ) that lead to the asymmetric and adipogenic partitioning of nutrient-energy ( 114 ).…”

Genes and Diet in the Prevention of Chronic Diseases in Future Generations

“…Although the current evidence has been questioned by some studies [58,64,108], the data in the literature are accumulating in support of the potential role of epigenetic and genetic patterns of parents in offspring health. Therefore, comprehensive knowledge of the epigenetic modifications induced by unhealthy parental lifestyles or by exposure to environmental insults in the periconceptional period could provide useful insights for the prevention of long-term disease in the offspring.…”

“…The maternal resources hypothesis proposes a novel conceptualization of inheritance and evolution, in which non-genetic vectors, including accumulative maternal effects (i.e., maternal prenatal energy metabolism and maternal postnatal physical activity), socio-environmental and phenotypic evolution, are the predominant causal factors for the health of future generations [62]. Thus, in this evolutionary context, the "overconsumption" that leads to metabolic disease is due not to dietary factors per se, but rather to physical inactivity caused by increments in energy intake and non-genetic evolutionary processes with the adipogenic partitioning of nutrient-energy [62][63][64].…”