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The synthesis of fatty acids plays a critical role in shaping milk production characteristics in dairy cattle. Thus, identifying effective haplotypes within the fatty acid metabolism pathway will provide novel and robust insights into the genetics of dairy cattle. This study aimed to comprehensively examine the individual and combined impacts of fundamental genes within the fatty acid metabolic process pathway in Jersey cows. A comprehensive phenotypic dataset was compiled, considering milk production traits, to summarize a cow's productivity across three lactations. Genotyping was conducted through PCR-RFLP and Sanger sequencing, while the association between genotype and phenotype was quantified using linear mixed models. Moderate biodiversity and abundant variation suitable for haplotype analysis were observed across all examined markers. The individual effects of the FABP3 , LTF and ANXA9 genes significantly influenced both milk yield and milk fat production. Additionally, this study reveals novel two-way interactions between genes in the fatty acid metabolism pathway that directly affect milk fat properties. Notably, we identified that the GGAAGG haplotype in FABP3 × LTF × ANXA9 interaction may be a robust genetic marker concerning both milk fat yield and percentage. Consequently, the genotype combinations highlighted in this study serve as novel and efficient markers for assessing the fat content in cow's milk.

Fatty acid binding protein 3 (FABP3) is involved in signal transduction pathways, and in the uptake and utilization of long-chain fatty acids. However, the transcriptional regulation of FABP3 in goat is unclear. In this study, the FABP3 5' flanking region was amplified from goat ( Capra hircus ) genomic DNA. Luciferase reporter vectors containing promoter fragments of five different lengths were constructed and transfected into dairy goat mammary epithelial cells. The region of the promoter located between -1801 and -166 bp upstream of the transcription start site (TSS) exhibited the highest luciferase activity, and contained two cAMP response elements (CREs) located at -1632 bp and -189 bp. Interference with CREB1 significantly downregulated FABP3 promoter activity. In addition, FABP3 promoter activity was significantly reduced after mutation of the CRE1 (-1632 bp) and CRE2 (-189 bp) sites. Further analysis indicated that the CRE2 site was essential for the transcriptional activity induced by CREB1 . These results demonstrated that CREB1 is involved in the transcriptional regulation of FABP3 expression in the goat mammary gland via a direct mechanism, thus revealing a novel signaling pathway involved in fatty acid metabolism in goat.

Senile osteoporosis (OP) is often concomitant with decreased autophagic activity. OPTN (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, is found to play a pivotal role in selective autophagy, coupling autophagy with bone metabolism. However, its role in osteogenesis is still mysterious. Herein, we identified Optn as a critical molecule of cell fate decision for bone marrow mesenchymal stem cells (MSCs), whose expression decreased in aged mice. Aged mice revealed osteoporotic bone loss, elevated senescence of MSCs, decreased osteogenesis, and enhanced adipogenesis, as well as optn - / - mice. Importantly, restoring Optn by transplanting wild-type MSCs to optn - / - mice or infecting optn - / - mice with Optn -containing lentivirus rescued bone loss. The introduction of a loss-of-function mutant of Optn K193R failed to reestablish a bone-fat balance. We further identified FABP3 (fatty acid binding protein 3, muscle and heart) as a novel selective autophagy substrate of OPTN. FABP3 promoted adipogenesis and inhibited osteogenesis of MSCs. Knockdown of FABP3 alleviated bone loss in optn - / - mice and aged mice. Our study revealed that reduced OPTN expression during aging might lead to OP due to a lack of FABP3 degradation via selective autophagy. FABP3 accumulation impaired osteogenesis of MSCs, leading to the occurrence of OP. Thus, reactivating OPTN or inhibiting FABP3 would open a new avenue to treat senile OP. Abbreviations: ADIPOQ: adiponectin, C1Q and collagen domain containing; ALPL: alkaline phosphatase, liver/bone/kidney; BGLAP/OC/osteocalcin: bone gamma carboxyglutamate protein; BFR/BS: bone formation rate/bone surface; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CDKN1A/p21: cyclin-dependent kinase inhibitor 1A; CDKN2A/p16: cyclin dependent kinase inhibitor 2A; CDKN2B/p15: cyclin dependent kinase inhibitor 2B; CEBPA: CCAAT/enhancer binding protein (C/EBP), alpha; COL1A1: collagen, type I, alpha 1; Ct. BV/TV: cortical bone volume fraction; Ct. Th: cortical thickness; Es. Pm: endocortical perimeter; FABP4/Ap2: fatty acid binding protein 4, adipocyte; H2AX: H2A.X variant histone; HE: hematoxylin and eosin; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MAR: mineral apposition rate; MSCs: bone marrow mesenchymal stem cells; NBR1: NBR1, autophagy cargo receptor; OP: osteoporosis; OPTN: optineurin; PDB: Paget disease of bone; PPARG: peroxisome proliferator activated receptor gamma; Ps. Pm: periosteal perimeter; qRT-PCR: quantitative real-time PCR; γH2AX: Phosphorylation of the Serine residue of H2AX; ROS: reactive oxygen species; RUNX2: runt related transcription factor 2; SA-GLB1: senescence-associated (SA)-GLB1 (galactosidase, beta 1); SP7/Osx/Osterix: Sp7 transcription factor 7; SQSTM1/p62: sequestosome 1; TAX1BP1: Tax1 (human T cell leukemia virus type I) binding protein 1; Tb. BV/TV: trabecular bone volume fraction; Tb. N: trabecular number; Tb. Sp: trabecular separation; Tb. Th: trabecular thickness; μCT: micro computed tomography.