Several evolutionary hypotheses have been proposed to unmask the origin of obesity-related IR and T2D, e.g., the "thrifty genotype" hypothesis suggests that certain "thrifty genes" that helped hunter-gatherer populations efficiently store energy as fat during feast-famine cycles are now maladaptive in our modern obesogenic environment. The "drifty genotype" theory suggests that if thrifty genes were advantageous, they would have spread widely, but proposes genetic drift instead. The "behavioral switch" and "carnivore connection" hypotheses propose insulin resistance as an adaptation for a brain-dependent, low-carbohydrate lifestyle. The thrifty phenotype theory suggests various metabolic outcomes shaped by genes and environment during development. However, the majority of these hypotheses lack experimental validation. Understanding why ancestral advantages now predispose us to diseases may aid in drug development and prevention of disease. EM helps us to understand the evolutionary relation between obesity-related IR and T2D. But still gaps and contradictions persist. Further interdisciplinary research is required to elucidate complete mechanisms.
Keyphrases
- insulin resistance
- genome wide
- type diabetes
- metabolic syndrome
- adipose tissue
- high fat diet induced
- weight loss
- dna methylation
- high fat diet
- glycemic control
- polycystic ovary syndrome
- skeletal muscle
- weight gain
- copy number
- cardiovascular disease
- bioinformatics analysis
- genome wide identification
- physical activity
- genome wide analysis
- white matter
- body mass index
- early life
- transcription factor
- drug induced