Journal Article

Serum Metabolomics Reveals Carnitine Metabolism as a Possible Central Metabolic Axis of Pemafibrate Action

Qian, Chufang, Nakajima, Takero, Iwadare, Takanobu, Zhang, Xuguang, Zheng, Qianqian, Tanabe, Kazuhiro, Yuki, Sakura, Hayashi, Chihiro, Diao, Yifan, Tanaka, Naoki, Zhang, Zhe, Kimura, Takefumi, Yang, Xiyue, Nakamuta, Makoto, Kittaka, Hiroki, Chen, Jiali

2026

Overview

Pemafibrate (PEM), a novel selective peroxisome proliferator-activated receptor α modulator, is widely used to treat dyslipidemia, yet its systemic metabolic effects remain incompletely defined. We performed untargeted serum metabolomics in patients with hypertriglyceridemia at baseline and at 2 and 8 weeks after PEM treatment. PEM increased cystine, L-methionine, uridine, and L-carnitine, while decreasing lipid-related metabolites, including lysophosphatidylcholines, adenosine, and erucic acid (22:1). Circulating carnitine levels rose progressively, with a significant elevation at 8 weeks, whereas ketone bodies showed only modest, non-significant increases. Consistently, increases in circulating and tissue carnitine were also observed in male 8-week-old C57BL/6J mice treated with a clinically relevant dose of PEM for 2 weeks. Mechanistically, PEM did not significantly alter genes involved in carnitine biosynthesis or transport, but upregulated hepatic carnitine O-acetyltransferase and carnitine O-octanoyltransferase, key enzymes of carnitine utilization and turnover. Collectively, these findings suggest that enhanced carnitine metabolism represents an important metabolic axis of PEM action.