Narrative review explores nesfatin-1 in infertility, pregnancy, and lactation

Photo by Navy Medicine / Unsplash

Frontiers in Medicine Published May 11, 2026 Medically reviewed May 11, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Interpret nesfatin-1 levels cautiously in reproductive conditions due to heterogeneous findings and assay variability.

This narrative review synthesizes current evidence on the adipokine nesfatin-1 in the context of infertility, pregnancy complications, and lactation. The authors highlight that clinical studies in these areas report heterogeneous findings, with nesfatin-1 levels described as increased, decreased, or unchanged across similar clinical conditions. This variability underscores the complexity of nesfatin-1's role in reproductive physiology.

Key limitations identified include assay variability, timing of sampling, and population heterogeneity, which may contribute to the inconsistent results. The authors caution against interpreting nesfatin-1 as a straightforward biomarker, emphasizing that it should be viewed as a context-dependent endocrine integrator.

The review does not provide pooled effect sizes or meta-analytic data, as it is a narrative synthesis. No specific interventions, comparators, or outcomes are reported. The practice relevance is not explicitly stated, but the findings suggest that clinical application of nesfatin-1 measurement remains uncertain due to the lack of consistent evidence.

Overall, this review underscores the need for standardized methodologies and larger, well-controlled studies to clarify nesfatin-1's potential role in reproductive health. Clinicians should interpret current data cautiously, recognizing the limitations and heterogeneity in the literature.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

Nesfatin-1, a peptide derived from nucleobindin-2 (NUCB2), is a widely expressed neuroendocrine factor originally identified for its anorexigenic effects in the central nervous system. Beyond energy homeostasis, accumulating evidence implicates nesfatin-1 in the regulation of glucose metabolism, stress-axis activity, inflammation, and reproductive function. These properties make nesfatin-1 particularly relevant to human reproduction and early life, physiological states characterized by profound metabolic and endocrine adaptations. The objective of this review is to examine whether nesfatin-1 functions as an integrative endocrine signal linking metabolic, stress-related, and reproductive pathways across the reproductive life course. We synthesize current human evidence on nesfatin-1 in infertility, assisted reproductive technologies, pregnancy adaptations and complications, the maternal–fetal interface, lactation, and postpartum metabolic recovery. Nesfatin-1 has been detected in several biological compartments relevant to reproductive physiology, including maternal plasma, follicular fluid, amniotic fluid, cord blood, and human breast milk. Clinical studies investigating these compartments report heterogeneous findings, with nesfatin-1 levels described as increased, decreased, or unchanged across similar clinical conditions. This variability likely reflects the context-dependent regulation of nesfatin-1 by metabolic status, stress-axis activation, inflammatory signaling, and reproductive stage. In this review, we synthesize current human evidence on nesfatin-1 across the continuum of reproduction, pregnancy, early development, and lactation, and propose a framework to reconcile these inconsistent findings. We argue that nesfatin-1 should be viewed as a context-dependent endocrine integrator reflecting the interaction of metabolic, stress-related, inflammatory, and reproductive axes rather than as a unidirectional biomarker. We further highlight key methodological challenges, including assay variability, timing of sampling, and population heterogeneity, and discuss the potential of nesfatin-1 as a longitudinal or stratification biomarker in reproductive endocrinology. Finally, we outline priorities for future research to clarify its physiological role and translational relevance in human reproduction and early life.