Androgen Excess Uncouples Circulating and Hepatic Lipid Homeostasis in Females on a High-Calorie Diet

However, its impact on hepatic lipid regulation remains poorly understood with conflicting results. In age and weight matched female mice, dihydrotestosterone (DHT) treatment under a regular chow diet did not alter hepatic or circulating lipid levels.

In contrast, under a western diet, DHT protected against metabolic dysfunction–associated steatotic liver disease (MASLD) by reducing hepatic triglyceride (TG) accumulation, even as it exacerbated systemic hypertriglyceridemia. These effects occurred without changes in hepatic insulin–Akt signaling and were independent of hepatic androgen receptor (AR) signaling. Multiomics profiling revealed that DHT reprogrammed hepatic transcription toward a male like pattern driven by pulsatile growth hormone (GH)–STAT5 signaling.