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
Metabolic diseases and age-related disorders represent an increasing global health challenge in the 21st century, accounting for a substantial proportion of morbidity, mortality, and healthcare expenditure worldwide [, ].；However, persistent or unresolved stress promotes chronic low-grade inflammation, ectopic fat deposition, and insulin resistance, contributing to progressive metabolic dysfunction, which can also accelerate biological aging [–].；However, it remains unclear whether their induction during metabolic disease reflects adaptive or compensatory responses, and whether their effects are beneficial or detrimental depending on the context (Fig. ).
方法
However, GDF15 treatment also promotes energy expenditure in the skeletal muscle of mice through a GFRAL/β-adrenergic signaling axis, sustaining fatty acid oxidation and calcium futile cycling, which helps to prevent the reductions in energy expenditure during caloric restriction [].；A large prospective cohort study showed that individuals who developed T2D had higher baseline GDF15 levels than those who did not.；For this review, studies labeled as NAFLD were included as MASLD, as they largely overlap with the current diagnostic criteria for MASLD.
核心结论
Metabolic diseases, including obesity, type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD), are also closely associated with aging [].；However, persistent or unresolved stress promotes chronic low-grade inflammation, ectopic fat deposition, and insulin resistance, contributing to progressive metabolic dysfunction, which can also accelerate biological aging [–].；However, it remains unclear whether their induction during metabolic disease reflects adaptive or compensatory responses, and whether their effects are beneficial or detrimental depending on the context (Fig. ). ‖ 结论：Interestingly, our integration of the available evidence not only highlights complementary and partially overlapping functions of FGF21 and GDF15 in the regulation of energy balance and cellular stress but also identifies emerging evidence of cross-regulation between them, which appears to be highly dependent on the tissue and context.
局限
In contrast, other studies have reported that although FGF21 signaling to WAT is required for acute insulin sensitization, FGF21 administration does not increase plasma adiponectin levels, indicating that adiponectin may not be required for the metabolic effects of FGF21 [].；Further studies have shown that fatty acids increase GDF15 levels and reduce food intake in WT mice through the GDF15-GFRAL axis, as this effect disappears in mice lacking Gfral [, ].
对本项目的价值
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全文来源
PMC JATS 全文（正文 94,677 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Biological functions and emerging interplay of FGF21 and GDF15 in metabolic diseases and aging.
- 期刊与标识：Mol Biomed · PMID 42957849 · DOI 10.1186/s43556-026-00627-w
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