The Thrifty Gene Theory By Aimee Velk

What is the thrifty gene theory? posits that the human genome is evolved for survival in the late Paleolithic era (50,000 to 10,000 BC) humans were subject to intermittent bouts of feast & famine and constant physical activity early humans may have benefitted by prioritizing storage of nutrients during times of plenty

That’s not beneficial today. sedentary lifestyle + abundant energy- dense diet Genetic adaptation may not occur as fast lifestyle change Possible link to modern increase in T2DM & obesity

What is meant by the thrifty gene? Collective term for storage-promoting action Perixisome proliferator-activated receptor (PPAR) transcription factor Ligand-activated receptors

What is meant by the thrifty gene? protein (3 isoforms, ą, γ, & δ,) which influences genetic expression acts on region of genome associated with metabolic genes i.e. they influence genetic expression during the construction of mRNA inside the nucleus of a cell

A Quick Review of DNA Replication

The Clinical Studies Intervention 1 Intervention 2 13 dyslipidemic men w/ central obesity Received dose of PPAR- δ agonist or placebo Focused on effect of PPAR- δ on lipoprotein metabolism Intervention 2 8 healthy 25 yo. men All subjects fasted intermittently for 15 days Focused on possible link b/w PPAR-γ & insulin sensitivity

Intervention 1: PPAR-δ 3-wk. wt. maintenance before study 6-wk double-blind crossover trial w/2-wk wash-out period b/w trials Serum concentrations of lipoproteins were averaged

Results PPAR-δ activity induced by agonisit: decreased TAG content of lipoproteins positively changed LDL composition

Mean VLDL, IDL, LDL, and HDL triglyceride (A) and cholesterol (B) content ± sem during placebo (closed square) and GW501516 (open square). *, P < 0.05. Mean VLDL, IDL, LDL, and HDL triglyceride (A) and cholesterol (B) content ± sem during placebo (closed square) and GW501516 (open square). *, P < 0.05. Ooi E M M et al. JCEM 2011;96:E1568-E1576 ©2011 by Endocrine Society

Relevance Ligand activation of PPAR-δ may result in favorable genetic regulation of lipid metabolism Evidence of a strong relationship between PPAR-δ and lipid metabolism supports the thrifty gene hypothesis.

Intervention 2: PPAR-γ Intermittent Fasting for 15 days: -fasting for 20 hrs every other day for 15 days Measured insulin response in subjects before and after trial

Results After Fasting: -Increased glucose infusion rate -steadier blood glucose levels

Relevance Faster glucose infusion rate demonstrates better insulin function, increased sensitivity Steady BG demonstrates better glucose control

Limitations Small, 13 participants and 8 participants Limited to 1 demographic Questions?