All forms of life share the ability to sense environmental change and respond in real time by engaging adaptive homeostatic programs. In higher organisms, the composition of consumed meals presents a complex, constantly changing nutritional environment, and we are only beginning to understand the sensing and signaling systems that detect and coordinate the transcriptional, physiological, and behavioral responses to meal components. Although it has long been axiomatic that dietary composition plays a deterministic role in overall health, the growing prevalence of obesity and metabolic syndrome has prompted a refocus of attention on the significance of dietary macronutrients to health outcomes. Findings from earlier investigations of potential roles for dietary carbohydrates and fat in disease progression or remediation (1–4) are now being reframed by experimental evidence linking dilution of dietary protein to compensatory increases in ingestive behavior (5,6). Recent studies also illustrate that modifying dietary essential amino acid (EAA) composition has profound effects on lipid metabolism and energy balance (7–10). A consensus is emerging to support the view that protein intake is monitored through nutrient-sensing mechanisms that detect changes in EAAs and provide regulatory input to both energy balance and the integration of carbohydrate and lipid metabolism (5,6,11,12). We will examine the transcriptional and metabolic responses to EAA deprivation or restriction to make the broader case that EAA sensing and signaling play an essential role in coordinating metabolic responses to dietary composition, particularly the content and composition of dietary protein.
Nutrient sensing and protein nutrition
Protein leverage hypothesis.
Simpson and Raubenheimer (11) used an integrative modeling approach to develop a geometric framework for evaluating the impact of dietary macronutrients on response variables such as nutrient selection, body composition, longevity, and reproduction. The geometric framework model of nutrition was originally developed and tested in experiments in which life …