What question did this study set out to answer?

To explore the role of CPT2 in fetal growth restriction and the effect of fenofibrate on placental lipid metabolism.

May 6, 2026

Fenofibrate Restores Fatty Acid Oxidation in CPT2-Deficient Placenta to Attenuate Fetal Growth Restriction ID 1114

Key Points

To explore the role of CPT2 in fetal growth restriction and the effect of fenofibrate on placental lipid metabolism.
Utilized human serum, placenta, FGR mice, and trophoblast cells in experiments.
Employed siRNA transfection for gene knockdown of CPT2.
Conducted lipidomics and proteomics for mechanism exploration.
Assessed cellular functions through proliferation, migration, and invasion assays.
Evaluated fetal growth via metrics like newborn weight and placental efficiency.
FGR models showed increased lipid accumulation and decreased CPT2 expression in the placenta.
Silencing CPT2 disrupted trophoblast cell metabolism and functions.
Administration of fenofibrate significantly restored CPT2 expression and fatty acid oxidation levels.
Improved fetal weight and placental efficiency observed following fenofibrate treatment.

Abstract

INTRODUCTION: Lipid metabolic homeostasis is essential for healthy embryonic growth and development. Carnitine palmitoyltransferase 2 (CPT2), a key regulator of mitochondrial fatty acid β-oxidation, plays a critical role in this process, yet its involvement in fetal growth restriction (FGR) remains insufficiently explored. METHODS: Human serum and placenta, FGR mice, and trophoblast cells were used. siRNA transfection was utilized for gene knockdown. Lipidomics and proteomics were performed for mechanism exploration. The assays of proliferation, migration, and invasion were employed to assess the cellular biological functions. To evaluate the growth status in mice, the weight of the newborn mice, the placental efficiency, and histological characteristics were examined. RESULTS: Results demonstrate that both FGR patients and mouse models exhibit increased maternal serum and placental lipid accumulation, accompanied by significantly decreased placental CPT2 expression and diminished fatty acid oxidation. Silencing CPT2 disrupts trophoblast cell metabolism, proliferation, migration, and invasion, highlighting its importance in cellular function. Placental PPARα expression is also notably reduced in FGR, further compromising lipid metabolism. In FGR mice, fetal weight and placental efficiency are markedly reduced. Importantly, administration of fenofibrate, a PPARα agonist, significantly upregulates CPT2 expression, restores placental lipid oxidative capacity, and improves fetal growth and placental function in FGR models. CONCLUSIONS/IMPLICATIONS: Findings underscore the pivotal role of CPT2 in placental lipid metabolism and trophoblast biology, directly affecting fetal development. Targeting the PPARα–CPT2 axis with fenofibrate emerges as a promising and effective therapeutic approach for improving outcomes in FGR, offering a new direction for clinical intervention in this challenging pregnancy complication.

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