Figure 1

A depiction of how natural selection of thrifty genotype, which was a physiological adaptive mechanism for human survival, on the current obesogenic environment, is maladaptive to disease phenotype. Our ancestors were often faced with survival stresses, including famine, infection, trauma and physical stress. For example, an acute inflammatory episode may cause water loss, high energy consumption and activation of the innate and adaptive immune system. To cope with the injury responses, an elegant coordination of neuroendocrine, energy storage and immune systems are adapted. Inflammatory cytokines released from activated immune cells inhibits insulin signaling pathway; as a result, plasma levels of glucose are elevated to provide energy sources to maintain the function of vital organs (heart, brain and immune cells) and combat for the infection. In addition, water loss and sodium deprivation due to insufficient sodium intake or excess sodium loss may activate rennin-angiotensin-aldosterone system (RAAS), sympathetic nerve or neuro-endocrine system to preserve sodium and body fluid and increase blood pressure. As results of natural selection, the survival pressures drove our evolution to shape a thrifty genotype, which favored/promoted energy-saving and sodium preservation. With the switch to a sedentary lifestyle and sodium- and energy-rich diets (current obesogenic environment), the thrifty genotype is no longer advantageous, and may be maladaptive to disease phenotype, resulting in hypertension, obesity and insulin resistance syndrome.