Systemic Acetate Is a Potential Biomarker of Metabolic Health and Therapeutic Response: A Pilot Cross-Sectional Investigation

Abstract

Background: The negative metabolic effects of persisting obesity are progressive in nature and at one point predispose to the development of type II diabetes. Systemic levels of acetate reportedly fluctuate with the development of the obese state, but it has been controversial whether the levels increase or decrease and a paucity of information exist on the levels of the molecular anion in the obese diabetic state, and also after treatment. In this pilot cross-sectional investigation, the objective was to determine evidence of longitudinal changes in systemic acetate with the progression of metabolic disease from the lean to the obese and diabetic states and whether the changes are reversed with treatment.

Methods: A cross-sectional analysis was performed on a cohort of male subjects who were then categorized to either the lean, obese, untreated obese diabetic states or obese diabetic state treated with a therapeutic regimen comprised primarily of metformin. Fasting serum acetate was measured in the subjects and reported along with other common metabolic parameters.

Results: Compared to the lean group (67 37 µM), the average level of acetate was elevated in the obese group (151 81 µM), and significantly more in the untreated obese diabetic group (365 111 µM; diabetic vs. lean, P value < 0.001; diabetic vs. obese, P value < 0.01). The treated obese diabetic patients showed significantly reduced concentrations relative to the untreated (172 163 µM; treated vs. untreated, P value < 0.01), and their average level was not different from the lean and obese groups. Acetate levels in the pooled groups were positively associated with fasting glucose concentrations and HbA1c levels (P value = 0.02 and 0.014, respectively), but not with the body mass index (BMI) of the subjects.

Conclusions: These results are indicative of progressive increases in systemic acetate with metabolic transitioning from the lean into the obese and diabetic states, and which reverse course with treatment. These findings are limited by the small sample size, but agree with several contemporary reports, and together help establish the levels of systemic acetate as a biochemical index to longitudinally evaluate whole body metabolism and energy homeostasis, detect pathogenic transitions, and monitor therapeutic effectiveness.

J Endocrinol Metab. 2024;14(4):166-173
doi: https://doi.org/10.14740/jem943