Testosterone deficiency synergistically exacerbates fructose-induced hepatic steatosis through gut microbiota and pyruvate in mice

American Journal of Physiology-Endocrinology and Metabolism 2026 Open access

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Authors: Hiroki Takahashi, Naoki Harada, Yohei Hayamizu, Erdenetsogt Dungubat, Masami Nakazawa, Tomoya Kitakaze, Keiichiro Sugimoto, HIROSHI INUI, Eiji YOSHIHARA, Yoshihisa Takahashi, Ryoichi Yamaji
DOI: 10.1152/ajpendo.00518.2025
Cited by: 2
References: 63

Abstract

The combined effects of the factors that cause liver dysfunction are unclear. Here, we show that fructose intake and testosterone deficiency synergistically induce intestinal pyruvate accumulation and hepatic steatosis by altering gut microbiota and hepatic gene expression. Our findings provide a notion that pyruvate plays a novel role in hepatic steatosis. Moreover, our results suggest that risk factors for hepatic steatosis can exert a greater impact on disease development through complex mechanisms under certain conditions.

Fields of Study & Subjects

Diet Metabolism and Disease Liver Disease Diagnosis and Treatment Gut microbiota and health

Publication details

Journal / source
American Journal of Physiology-Endocrinology and Metabolism
Publisher
American Physiological Society
Volume
330
Issue
2
Pages
E233–E246
Publication date
7 January 2026
Language
EN