Systemic inhibition of <i>de novo</i> purine biosynthesis prevents weight gain and improves metabolic health by increasing thermogenesis and decreasing food intake.

ABSTRACT:

Objective

Obesity is a major health concern, largely because it contributes to type 2 diabetes mellitus (T2DM), cardiovascular disease, and various malignancies. Increase in circulating amino acids and lipids, in part due to adipose dysfunction, have been shown to drive obesity-mediated diseases. Similarly, elevated purines and uric acid, a degradation product of purine metabolism, are found in the bloodstream and in adipose tissue. These metabolic changes are correlated with metabolic syndrome, but little is known about the physiological effects of targeting purine biosynthesis.

Methods

To determine the effects of purine biosynthesis on organismal health we treated mice with mizoribine, an inhibitor of inosine monophosphate dehydrogenase 1 and 2 (IMPDH1/2), key enzymes in t

SUBMITTER: Myers JW 

PROVIDER: S-EPMC11566042 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature