title: Theodore E. Woodward award. The evolution of obesity: insights from the mid-Miocene.
abstract: All humans are double knockouts. Humans lack the ability to synthesize vitamin C due to a mutation in L-gulono-lactone oxidase that occurred during the late Eocene, and humans have higher serum uric acid levels due to a mutation in uricase that occurred in the mid Miocene. In this paper we review the hypothesis that these mutations have in common the induction of oxidative stress that may have had prosurvival effects to enhance the effects of fructose to increase fat stores. Fructose was the primary nutrient in fruit which was the main staple of early primates, but this food likely became less available during the global cooling that occurred at the time of these mutations. However, in today's society, the intake of fructose, primarily in the form of added sugars, has skyrocketed, while the intake of natural fruits high in vitamin C has fallen. We suggest that it is the interaction of these genetic changes with diet that is responsible for the obesity epidemic today. Hence, we propose that Neel's thrifty gene hypothesis is supported by these new insights into the mechanisms regulating fructose metabolism.
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado, Denver, CO 80016, USA. Richard.johnson@ucdenver.edu
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: Peter
authors.initials: P
authors.lastname: Andrews
authors.forename: Steven A
authors.initials: SA
authors.lastname: Benner
authors.forename: William
authors.initials: W
authors.lastname: Oliver
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000096:biosynthesis; D001363:Awards and Prizes; D005075:Biological Evolution; D001717:Birds; D004032:Diet / Q000009:adverse effects; D005632:Fructose / Q000008:administration & dosage / Q000378:metabolism; D049690:History, Ancient; D015186:Hominidae / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D050544:L-Gulonolactone Oxidase / Q000235:genetics; D008954:Models, Biological; D009154:Mutation; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D014503:Urate Oxidase / Q000235:genetics; D014527:Uric Acid / Q000378:metabolism
chemical_list: D014527:Uric Acid; D005632:Fructose; D050544:L-Gulonolactone Oxidase; D014503:Urate Oxidase; D001205:Ascorbic Acid