Postprandial Uridine Physiology Is Altered by Obesity

Dear Editors:

We read the recent article written by Deng et al¹ in Science with interest wherein plasma uridine dynamics were linked to thermoregulation. They report that plasma uridine levels decrease to 50% of baseline by 120 minutes after a meal, without similar changes in uric acid. Interestingly, these observations were made in a cohort of subjects with a mean body mass index of 28 kg/m². Obesity is a well-understood pathologic condition, wherein many physiologic responses are altered, including postmeal thermogenesis.² Further, uridine is a molecule that, just like bile acids, is excreted from the liver in bile. We have previously reported that the physiologic postmeal serum bile acid peak is delayed in obesity.³ We therefore hypothesized that postmeal uridine metabolism would also be altered in obesity.

In this letter, we submit data measuring the postmeal uridine and uric acid dynamics for a cohort of adolescents from our previously published study with severe obesity, both before and after weight loss from vertical sleeve gastrectomy. Before surgery, the participants were 17.4 ± 0.5 years old with a mean body mass index of 51.5 ± 2.5 kg/m². At 1 and 3 months after surgery, we observed weight loss in all participants.³

Herein we report that the mean plasma level of uridine increased, rather than decreased, in obese subjects after a meal. Furthermore, this pattern did not change with weight loss after bariatric surgery (Figure 1A). Postprandial plasma uric acid levels were higher in our subjects preoperatively (456.90 ± 26.43 μmol/L vs 508.3 ± 34.87 μmol/L; P = .004), 1 month after surgery (447.30 ± 33.8 μmol/L vs 541 ± 34.06 μmol/L; P = .0051) and 3 months after surgery (427.70 ± 28.56 μmol/L vs 514.80 ± 60.80 μmol/L; P = .0293; Figure 1B). Further, we observed a direct correlation of baseline fasting plasma uric acid and uridine levels (r = 0.74; P = .007).

Figure 1.

(A) Plasma uridine as percentage of baseline for presurgery (n = 10); 1 month after surgery (n = 9), and 3 months after surgery (n = 8; mean ± standard error of the mean). (B) Plasma uric acid presurgery (n = 10); 1 month after surgery (n = 9), and 3 months after surgery (n = 8).

To summarize, Deng et al¹ observed a change in uridine dynamics and mechanistically linked it to thermoregulation, while delinking it from uric acid metabolism. We studied both uridine and uric acid postmeal dynamics in a cohort with a much higher mean body mass index and observed contrary results. Further, we observed that the expected physiologic correlation of uric acid to uridine was maintained in our cohort. A high plasma concentration of glucose also triggers glycogenesis in the liver,⁴ which in turn can increase uridine in the systemic circulation.⁵ It is well-established that individuals who are obese have altered thermogenesis and basal metabolic rates.⁶ Recent reports further suggest that adaptive thermogenesis and resting metabolic rates are both blunted after gastric bypass.⁷ In this context, our contrarian observations of altered uridine postmeal excursions that persist despite weight loss warrant further investigation. We propose that there may potentially be an important mechanistic role for uridine in the persistent impaired thermoregulation observed in subjects with obesity, even after surgically induced weight loss.