ACLY facilitates alanine flux in the livers of db/db mice: a hyperpolarized [1-13C]pyruvate MRS study.

ABSTRACT:

Introduction

Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) feature paradoxical increases in both gluconeogenesis and lipogenesis. ATP citrate lyase (ACLY) supports both processes by generating cytosolic acetyl-CoA and oxaloacetate from citrate. While ACLY's role in lipogenesis is well established, its involvement in amino acid-driven gluconeogenesis remains unclear.

Methods

Using hyperpolarized [1-¹³C]pyruvate magnetic resonance spectroscopy (MRS), we observed [1-¹³C]alanine labeling in the livers of db/db mice. To test the effect of ACLY inhibition, mice were treated with BMS-303141, and blood glucose responses, hyperpolarized alanine labeling, and aminotransferase activity were evaluated. Western blotting was performed

SUBMITTER: Choi YS 

PROVIDER: S-EPMC12597765 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature