How does the inability to produce vitamin C helped weight gain? I recently wondered how do dogs cope without vitamin C intake like us. A few Wikipedia pages later, I learned that our dry-nosed ancestors lost about two-thirds of the gene responsible for vitamin C synthesis some 63 millions years ago. And then this passage: > Johnson et al. have hypothesized that the mutation of the GULOP (pseudogene that produces L-gulonolactone oxidase) so that it stopped producing GULO may have been of benefit to early primates by increasing uric acid levels and enhancing fructose effects on weight gain and fat accumulation. With a shortage of food supplies this gave mutants survival advantage. (Wikipedia: L-gulonolactone oxidase) I'm curious about the interaction (GULO/uric acid/fructose effects/fat storage) quoted above.

The effect comes indirectly since lower levels of ascorbate increases urate levels, according to

> Arthritis Rheum. 2005 Jun;52(6):1843-7.
>
> The effects of vitamin C supplementation on serum concentrations of uric acid: results of a randomized controlled trial.
>
> Huang HY1, Appel LJ, Choi MJ, Gelber AC, Charleston J, Norkus EP, Miller ER 3rd.

So the direct weight gain effect is due to increased levels of uric acid.

Further in the chain of events is that

> Recent studies show that fructose-induced uric acid generation causes mitochondrial oxidative stress that stimulates fat accumulation independent of excessive caloric intake.

according to

> Diabetes 2013 Oct; 62(10): 3307-3315.
>
> Sugar, Uric Acid, and the Etiology of Diabetes and Obesity
>
> Richard J. Johnson1,2⇑, Takahiko Nakagawa1,3, L. Gabriela Sanchez-Lozada4, Mohamed Shafiu5, Shikha Sundaram6, Myphuong Le1, Takuji Ishimoto1, Yuri Y. Sautin7 and Miguel A. Lanaspa1