Impaired mitochondrial ketone body oxidation in insulin resistant states.

ABSTRACT:

Background

Reduced mitochondrial respiratory function has been implicated in metabolic disorders like type 2 diabetes (T2D), obesity, and metabolic dysfunction-associated steatotic liver disease (MASLD), which are tightly linked to insulin resistance and impaired metabolic flexibility. However, the contribution of the ketone bodies (KBs) β-hydroxybutyrate (HBA) and acetoacetate (ACA) as substrates for mitochondrial oxidative phosphorylation (OXPHOS) in these insulin resistant states remains unclear.

Methods

Targeted high-resolution respirometry protocols were applied to detect the differential contribution of HBA and ACA to OXPHOS capacity in heart, skeletal muscle, kidney, and liver of distinct human or murine cohorts with T2D, obesity, and MASLD.

Findings

In humans

SUBMITTER: Zweck E 

PROVIDER: S-EPMC12657344 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature