ACSS1 Links Nutrient Overload to Impaired Bone Formation in Mouse Models
Published in Biology, Diseases!, Journals.
Published October 20, 2026.
Researchers have identified a metabolic pathway that links nutrient overload to impaired bone formation in experimental models. The study by Lu Gao, Zhuolei Yuan and colleagues appeared in Nature Communications on October 20.
The team found that excess glucose, alcohol or acetate increased the enzyme ACSS1 in bone marrow skeletal stem cells. This shifted acetate metabolism toward excessive acetyl-CoA production, disrupted mitochondrial function and reduced the cells’ capacity to form bone.
A key step involved abnormal acetylation of ME2, a mitochondrial enzyme. Its inactivation disturbed metabolic and redox balance, reinforcing oxidative stress and further mitochondrial dysfunction.
Deleting Acss1 or delivering an acetylation-resistant ME2 variant to bone-forming precursor cells restored mitochondrial resilience and bone formation in male mouse models of type 2 diabetes or chronic alcohol exposure. The interventions protected against the bone deterioration studied in those models.
These findings suggest a potential target for future therapies, but they do not demonstrate a treatment for osteoporosis or osteonecrosis in humans. The authors disclose a pending patent related to ME2 delivery. The peer-reviewed article is available ahead of final editorial changes.
Source: Gao, Yuan and colleagues, Nature Communications, October 20, 2026.