control group. They will then slowly gain weight at the same “normal” slow rate as the control group.
When the hormonal profiles and energy expenditure of the under-fed vs the over-fed groups are compared we find a very different profile. Historically we in the medical profession have been trying to design a better plan for the “under-fed” state. Instead we need to find a way to create the physiologic profile of the “over-fed” state, which results in natural shedding of excess energy storage.
A math exercise will reveal the bottom line of the energy balance problem. An energy mismatch of 11Kcal per day is a 0.4% error, and will increase body fat by approximately 45 pounds over an adult life. A mismatch of 30Kcal per day is a 1.5% error and results in a 200 pound increase over an adult life. Correction of these small but powerful errors is the goal of treatment.
The story of genetics and obesity begins in 1999 with the discovery of the FTO gene. Its significance would be revealed in 2007, when one of the Genomic Wide Association Studies (GWAS) of the human genome and chronic diseases was published. It showed a relationship between the FTO genetic locus and adiposity of the subjects. 4 Over the next several years a series of independent studies would all corroborate this genetic locus and the predisposition to obesity 5 6 7 8 9.
The next breakthrough was published in 2013 10. Researchers from the United Kingdom, Germany,and Japan analyzed 359 normal weight young volunteers of mixed european descent.They studied body composition, the FTO genotype, serum ghrelin response, and brain responses to food cues. The study shows a link between the FTO gene, Ghrelin, and alterations in psychologic functions that are linked to obesity.
In considering genetics we must also consider the role of “epi-genetics”. Wikipedia provides a nice accurate description:
Epigenetics is the study of heritable changes in gene activity that are not caused by changes in the DNA sequence; it also can be used to describe the study of stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable. Unlike simple genetics based on changes to the DNA
1 Centers for Disease Control. Obesity trends 2010
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