Male reproductive disorders are increasingly linked to metabolic diseases, but mechanistic research remains predominantly focused on the testis. The seminal microenvironment, shaped by epididymal and accessory-gland secretions, contains metabolites, lipids, ions, cytokines, extracellular vesicles, and microbial products, and may act as a metabolically responsive post-testicular interface that continues to influence sperm after spermatogenesis. Obesity, insulin resistance, dyslipidemia, and chronic inflammation can remodel this environment by disrupting secretory activity, redox homeostasis, immune signaling, and microbial ecology. These changes may converge on oxidative and inflammatory pathways, promoting membrane lipid peroxidation, mitochondrial dysfunction, impaired motility and capacitation, oxidative DNA base lesions, DNA fragmentation, and potentially epigenetic alterations. Mouse studies separately report obesity-associated epididymal vesicle remodeling and RNA-dependent changes in embryonic gene expression. In this Review, we examine the regulation and metabolic remodeling of the seminal microenvironment, how these changes may translate systemic metabolic stress into sperm injury, and emerging interventions including metabolic correction, antioxidant strategies, and microbiome-targeted approaches. Overall, current evidence remains largely observational and cross-sectional, with additional technical limitations in low-biomass seminal microbiome studies. Longitudinal and mechanistic studies are therefore needed to determine whether the seminal microenvironment is a causal mediator of metabolic infertility and a clinically tractable target for mechanism-guided preconception care.

Sphingolipids, a class of lipids, are widely present in the cell membranes of all eukaryotic and some prokaryotic organisms. These lipids play crucial roles in the formation of the lipid bilayer and are categorised into several groups, including sphingomyelins, ceramides, sphingosine-1-phosphate, and glycosphingolipids. In addition to their structural significance, sphingolipids also show bioactivity, regulating various signalling pathways involved in cell growth, differentiation, ageing, and apoptosis, and are closely associated with several chronic diseases, including obesity and type 2 diabetes mellitus. Notably, dysregulated sphingolipid metabolism contributes to obesity-related metabolic dysfunction through altered lipid accumulation, insulin signalling, organelle stress, and inflammation. This review summarises the various mechanisms and recent research advances related to sphingolipids and their association with obesity. It further examines how the metabolic effects of ceramides vary according to their acyl-chain length, enzyme of origin, tissue distribution, and metabolic context, as well as how adipose depot, sex, age, and metabolic phenotype influence the sphingolipid response to obesity. It further considers plant-derived sphingolipids as a compositionally distinct exogenous input to host sphingolipid pools, comparing their structural and enzymatic features with those of mammalian sphingolipids. Pharmacological, dietary, and lifestyle approaches that modify sphingolipid metabolism are also considered. Accordingly, the review summarises our current knowledge regarding the dietary occurrence, intestinal handling, and metabolic effects of sphingolipids and identifies the evidence gaps that currently limit conclusions regarding their relevance to obesity.