Alterations in Skeletal Muscle Insulin Signaling DNA Methylation: A Pilot Randomized Controlled Trial of Olanzapine in Healthy Volunteers.

Autor:	Burghardt KJ; Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA., Burghardt PR; Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202, USA., Howlett BH; Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA., Dass SE; Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA., Zahn B; Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA., Imam AA; Internal Medicine Department, College of Medicine, Umm Al-Qura University, Makkah 24381, Saudi Arabia., Mallisho A; Division of Endocrinology, School of Medicine, Wayne State University, Detroit, MI 48202, USA., Msallaty Z; Division of Endocrinology, School of Medicine, Wayne State University, Detroit, MI 48202, USA., Seyoum B; Division of Endocrinology, School of Medicine, Wayne State University, Detroit, MI 48202, USA., Yi Z; Department of Pharmaceutical Science, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48202, USA.
Jazyk:	angličtina
Zdroj:	Biomedicines [Biomedicines] 2024 May 10; Vol. 12 (5). Date of Electronic Publication: 2024 May 10.
DOI:	10.3390/biomedicines12051057
Abstrakt:	Antipsychotics are associated with severe metabolic side effects including insulin resistance; however, the mechanisms underlying this side effect are not fully understood. The skeletal muscle plays a critical role in insulin-stimulated glucose uptake, and changes in skeletal muscle DNA methylation by antipsychotics may play a role in the development of insulin resistance. A double-blind, placebo-controlled trial of olanzapine was performed in healthy volunteers. Twelve healthy volunteers were randomized to receive 10 mg/day of olanzapine for 7 days. Participants underwent skeletal muscle biopsies to analyze DNA methylation changes using a candidate gene approach for the insulin signaling pathway. Ninety-seven methylation sites were statistically significant (false discovery rate < 0.05 and beta difference between the groups of ≥10%). Fifty-five sites had increased methylation in the skeletal muscle of olanzapine-treated participants while 42 were decreased. The largest methylation change occurred at a site in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha ( PPARGC1A ) gene, which had 52% lower methylation in the olanzapine group. Antipsychotic treatment in healthy volunteers causes significant changes in skeletal muscle DNA methylation in the insulin signaling pathway. Future work will need to expand on these findings with expression analyses.
Databáze:	MEDLINE
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