时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
However, a subset of lean patients remains unclassifiable under either framework, underscoring the inherent limitations of current diagnostic criteria in fully capturing the heterogeneity of this population.；Although fibrates have been used for decades to modulate lipid profiles via PPARα activation, their efficacy in metabolic dysfunction-associated steatohepatitis (MASH) remains limited partly due to relatively low hepatoselectivity and potential off-target effects, and safety concerns persist.；These properties make them promising candidates for phenotype-specific management of lean MASLD, though large-scale clinical validation remains warranted.
方法
Notably, MASLD demonstrates superior applicability to lean individuals compared with MAFLD, as it relies on five routine cardiometabolic parameters while eliminating the requirement for homeostatic model assessment of insulin resistance and high-sensitivity C-reactive protein; in a well-characterized lean cohort, 83.5% fulfilled MASLD criteria versus only 49.4% under MAFLD.；However, a subset of lean patients remains unclassifiable under either framework, underscoring the inherent limitations of current diagnostic criteria in fully capturing the heterogeneity of this population.；Importantly, hepatic steatosis can be detected by sensitive imaging modalities such as controlled attenuation parameter even in some healthy, non-obese individuals without suspected liver disease, underscoring that steatotic liver disease is not confined to overt obesity-associated presentations; moreover, lean st
核心结论
Despite these diagnostic complexities, the global burden of MASLD is substantial, affecting approximately 32.4% of the population, with rising prevalence and a notable shift toward younger age groups and normal-BMI phenotypes, especially in Asia, where lean MASLD accounts for a significant proportion of cases, , .；Although traditionally associated with obesity, diabetes, and dyslipidemia, MASLD can develop in individuals who appear metabolically normal on conventional assessment due to visceral adiposity, excessive dietary fructose or saturated fat intake, and genetic susceptibility (e.g., PNPLA3 rs738409), yet may harbor subclinical metabolic disturbances such as insulin resistance and low-grade inflammation,.；Importantly, hepatic steatosis can be detected by sensitive imaging modalities such as controlled attenuation parameter even in some healthy, non-obese individuals without suspected liver disease, underscoring that steatotic liver disease is not confined to overt obesity-associated presentations; moreover, lean steatotic liver disease is now recognized as a distinct clinical e ‖ 结论：In conclusion, while significant progress has been made in understanding the pivotal role of PPARα in lean MASLD, much remains to be explored.
局限
First, there is a lack of animal models that accurately replicate human lean MASLD, as its pathogenesis involves complex interactions among genetic, environmental, and behavioral factors.；Furthermore, the heightened lipolytic activity of visceral fat and its direct effects on the liver warrant additional investigation.；The role of other nuclear receptors including FXR and LXR, in lean MASLD warrants attention, particularly in the context of RXR competitive dynamics and the therapeutic potential of agents that simultaneously agonize PPARα and inverse-agonize LXR.
对本项目的价值
★☆☆☆☆ 代谢轴既干预敏感性最高，也是老药新用供给最充足的来源。
全文来源
PMC JATS 全文（正文 134,141 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Emerging insights into PPARα's role in lean metabolic dysfunction-associated steatotic liver disease: Implications for targeted therapies.
- 期刊与标识：Acta Pharm Sin B · PMID 42948748 · DOI 10.1016/j.apsb.2026.06.029
A 级证据分级：A 级（同行评议人体研究）
本文属人体研究证据，但需注意：观察性或小样本干预的结论不等于已证实临床获益；效应量与长期安全性仍需更大规模、更长随访的试验验证。
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