Thrifty Genotype

The thrifty genotype hypothesis is the theory that during times of famine, genes that efficiently stored fat and maintained blood glucose levels, aided survival (Stannard & Johnson, 2003).  During times of food scarcity, visceral fat and intramyocellular triglyceride (IMTG) stores increased to provide alternative substrate.  These stores were utilized to maintain energy and insulin resistance helped to maintain blood glucose levels for brain function.  After prolonged fasting, immediate energy storage occurred during the feast phase of the cycle (Chakravarthy & Booth, 2004).  These thrifty genes were essential for survival. 

Today, thrifty storage of triglycerides and glycogen occur but in the absence of energy expenditure.  “Food scarcity” is now a constant cycle of “food abundance” and the cycle of feast, famine, physical activity, and rest are deregulated (Chakravarthy & Booth, 2004).  The thrifty genes are misexpressed and this leads to insulin resistance, lipotoxicity, and other metabolic complications.  The energy storage genotype and thrifty genes, that regulate hormone sensitive lipase (HSL), lipoprotein lipase (LPL), and lipolysis, are life threatening and no longer survival mechanisms (Tenenbaum, Fisman, & Michael, 2003).  The accumulation of IMTG alter metabolism by interferring with the insulin-signaling pathway.  As a result, this leads to decreased fat breakdown, impaired insulin sensitivity, and impaired glucose uptake at the skeletal muscle level (Stannard & Johnson, 2003). 

Even though the “thrifty genotype” functioned to enable survival today, in our western society, the storage genotype leads to obesity, hypertension, lipotoxicity, and insulin resistance.