Recharacterizing the Metabolic State of Energy Balance in Thrifty and Spendthrift Phenotypes.
PURPOSE
The human thrifty phenotype hypothesis presupposes that lower 24-hour (24h) energy expenditure (24EE) during famine preserves body mass and promotes survival. The prevailing view defines thrifty individuals as having a lower 24EE during fasting. However, it is also plausible that the greater decline in 24EE during fasting in thrifty individuals is due to higher 24EE during energy balance conditions (ENBAL). Herein, we provide evidence that this is indeed the case.


METHODS
In 108 healthy subjects, 24EE was measured in a whole-room indirect calorimeter both during ENBAL and 24h fasting conditions. Subjects were categorized as thrifty or spendthrift based on the median value (-162 kcal/day) of the difference in 24EE (adjusted for body composition) between fasting and ENBAL conditions. Concomitant 24h urinary catecholamines were assessed by liquid chromatography-mass spectrometry.


RESULTS
Compared to ENBAL, 24EE decreased during 24h fasting by 172 kcal/day (standard deviation = 93; range, -470 to 122). A greater-than-median decrease in 24EE ("thriftier" phenotype) was due to higher 24EE during ENBAL (+124 kcal/day; P < 0.0001) but not to lower 24EE during fasting (P = 0.35). Greater fasting-induced increase in epinephrine was associated with concomitant lower decrease in 24EE (r = 0.27; P = 0.006).


MAIN CONCLUSION
The greater decrease in 24EE during acute fasting (which characterizes the thrifty phenotype) is not due to reduced metabolic rate during fasting but to a relatively higher 24EE during feeding conditions, and this decrease in 24EE during fasting is accompanied by a smaller increase in epinephrine. These results recharacterize the prevailing view of the short-term 24EE responses that define the human metabolic phenotypes. Clinical Trials: NCT00523627, NCT00687115, NCT02939404.
['Hollstein|Tim|T|', 'Basolo|Alessio|A|', 'Ando|Takafumi|T|', 'Votruba|Susanne B|SB|', 'Walter|Mary|M|', 'Krakoff|Jonathan|J|', 'Piaggi|Paolo|P|']
D000293:Adolescent D000328:Adult D001143:Arousal D001481:Basal Metabolism D001823:Body Composition D002153:Calorimetry, Indirect D002940:Circadian Rhythm D003430:Cross-Sectional Studies D002149:Energy Intake D004734:Energy Metabolism D005215:Fasting D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D010641:Phenotype D022722:Thermogenesis D055815:Young Adult
energy balance thrifty phenotype energy expenditure fasting epinephrine FGF21