时间标签：数据日期 2026-11-05 · 生成时间 2026-11-05 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/11/02 – 2026/11/06 ｜ 情报发生日期 2026-11-05
研究问题
However, whether NPAS2 directly regulates myocardial glucose and lipid metabolism in the setting of diabetic cardiomyopathy has not been previously reported.Pyruvate dehydrogenase (PDH) is the rate-limiting enzyme of the pyruvate dehydrogenase complex (PDHc), which catalyzes the irreversible oxidative decarboxylation of pyruvate to acetyl-CoA, thereby linking glycolysis to the tricarboxylic acid cycle and oxidative phosphorylation.；Nevertheless, whether NPAS2 governs PDH expression or activity in the heart, and whether such regulation is mechanistically relevant to diabetic cardiomyopathy, remains entirely unknown.In the present study, we hypothesized that NPAS2 serves as a critical upstream regulator of myocardial PDH activity and glucose oxidation, and that disruption of NPAS2 contributes to the metabolic and structural abnormalities observed in diabetic cardiomyopathy.；These data suggest that NPAS2 deficiency disrupts mitochondrial bioenergetics and promotes a metabolic shift toward lipid accumulation and impaired glucose oxidation.3.4Overexpression of NPAS2 attenuates HGHF-induced mitochondrial dysfunction, apoptosis, and metabolic perturbations in cardiomyocytesTo further validate the protective role of NPAS2 and explore its potential as a therapeutic target, we investigated whether restoring NPAS2 expression could mitigate HGHF-induced cellular damage.
方法
With the rapidly increasing global prevalence of diabetes, DCM has become a leading contributor to heart failure and cardiovascular mortality in diabetic patients (2).；Nevertheless, whether NPAS2 governs PDH expression or activity in the heart, and whether such regulation is mechanistically relevant to diabetic cardiomyopathy, remains entirely unknown.In the present study, we hypothesized that NPAS2 serves as a critical upstream regulator of myocardial PDH activity and glucose oxidation, and that disruption of NPAS2 contributes to the metabolic and structural abnormalities observed in diabetic cardiomyopathy.；To test this hypothesis, we first characterized the expression and circadian rhythmicity of NPAS2 in the myocardium of two independent diabetic mouse models.
核心结论
Accumulating evidence indicates that disruption of circadian rhythms is closely associated with the pathogenesis of metabolic diseases, including obesity, type 2 diabetes, dyslipidemia, and cardiovascular disorders (7, 8).；These findings highlight NPAS2 as a promising cardioprotective factor, yet its specific role in the diabetic myocardium has not been systematically explored.Emerging evidence has further linked NPAS2 to the regulation of glucose and lipid metabolism.；These observations demonstrate that NPAS2 can exert tissue-specific metabolic effects, and its functional output is likely dependent on the cellular context.
局限
However, whether NPAS2 directly regulates myocardial glucose and lipid metabolism in the setting of diabetic cardiomyopathy has not been previously reported.Pyruvate dehydrogenase (PDH) is the rate-limiting enzyme of the pyruvate dehydrogenase complex (PDHc), which catalyzes the irreversible oxidative decarboxylation of pyruvate to acetyl-CoA, thereby linking glycolysis to the tricarboxylic acid cycle and oxidative phosphorylation.；While significant challenges remain before clinical translation, our results provide a strong rationale for further preclinical development of NPAS2-based therapeutic strategies.4LimitationsWhile our study provides evidence supporting a protective role of NPAS2 in diabetic cardiomyopathy, several limitations should be acknowledged.；Finally, further studies are needed to determine whether NPAS2 influences additional metabolic pathways and broader systemic metabolic crosstalk, which may provide deeper insight into its role in diabetic cardiac remodeling.5ConclusionIn conclusion, we propose that NPAS2 acts as a critical guardian of myocardial metabolic homeostasis in diabetes by sustaining PDH activity and mitochondrial glucose oxidation.
对本项目的价值
中高价值：属「线粒体质量控制与氧化应激」方向；线粒体功能与氧化应激栏目可用作本项目文献库与综述素材。 ｜ 价值分 3.0/5（★★★☆☆）
全文来源
PubMed PMC JATS（正文 49,172 字符，题名指纹 0.83，已过 PubMed PMCID 官方关联 + 题名指纹 + 正文长度归属校验）
原文题录
- 中文题名：NPAS2 经维持丙酮酸脱氢酶活性与线粒体代谢稳态减轻糖尿病心肌病
- 英文标题：NPAS2 attenuates diabetic cardiomyopathy by preserving pyruvate dehydrogenase activity and mitochondrial metabolic homeostasis.
- 期刊与标识：Frontiers in cardiovascular medicine · PMID 42973465 · DOI 10.3389/fcvm.2026.1980726 · PMC PMC13724374