Pregnancy-to-lactation transition remodels mammary adipocytes via p38 MAPK-dependent adipogenesis

ABSTRACT: Adipose tissue remodeling is essential for mammary gland development and functional restoration. The dry period represents a pivotal phase characterized by extensive tissue remodeling as the gland transitions from pregnancy to lactation. However, the morphological and molecular mechanisms underlying mammary adipose tissue remodeling during this stage remain poorly understood. In this study, we investigated adipose remodeling in the mammary gland of dairy goats during this transitional period. An integrative multi-omics approach combining transcriptomics, lipidomics, and metabolomics was employed to comprehensively characterize the molecular changes of mammary tissue. Histological analysis and transmission electron microscopy revealed a substantial increase in both the proportion and size of adipocytes at 4 wk before prepartum. RNA sequencing of isolated mammary adipose cells indicated that the p38 mitogen-activated protein kinase (MAPK) pathway may play a key regulatory role in this process. To further dissect its function, we established an immortalized goat mammary preadipocyte cell line. Pharmacological inhibition of p38 MAPK significantly impaired adipocyte differentiation and hypertrophy. Furthermore, our findings suggested that p38 MAPK modulates adipogenesis in mammary adipocytes through downstream effectors, including apolipoprotein E. These findings highlight a critical role for the p38 MAPK signaling pathway in orchestrating mammary adipose tissue remodeling during the dry period. This work provides novel insights into the molecular regulation of mammary gland renewal and offers potential targets to manipulate mammary gland development in ruminants.