Simple SummaryA 6-month-old male Korean native calf, known for its highly marbled meat, was purchased but found dead three days later, without any notable medical history. The calf had a significantly higher body weight than average for its age. Postmortem examination revealed fat necrosis, along with gastric dilatation, volvulus and intestinal obstruction, as the cause of death. Serum chemistry analysis indicated disrupted lipid metabolism and pancreatic damage—obstructive acute pancreatitis. To investigate the cause of fat necrosis, microRNA patterns were analyzed. Interestingly, the results resembled those found in human patients with diabetes mellitus. To explore the potential correlation between fat necrosis and human diabetic-like miRNA patterns, a comprehensive analysis of miRNAs and the miRNA-mediated Kyoto Encyclopedia of Gene and Genome (KEGG) pathway were conducted. The bovine target gene prediction and KEGG analysis indicated a significant association between multiple genes and diabetic-like clinical conditions. These findings suggest fat necrosis can occur in high-spec cattle such as Korean native calves, and in such cases clinical indicators such as diabetes are observed, providing the factors contributing to the breed’s high meat quality and marbling. The in-depth analysis of miRNA and the KEGG pathway offers valuable insights into the potential mechanisms underlying this correlation.AbstractKorean native cattle are highly valued for their rich marbling and flavor. Nonetheless, endeavors to enhance marbling levels can result in obesity, a prevalent contributor to fat necrosis. Fat necrosis is characterized by the formation of necrotic fat masses in the abdominal cavity, which physically puts pressure on affected organs, causing physical torsion or obstruction, resulting in death and consequent economic loss. Pancreatic injuries or diabetes mellitus were reported as factors of fat necrosis in humans; however, the pathogenesis in animals has not been established. In this study, we identified fat necrosis in a 6-month-old Korean native cow and investigated its potential underlying causes. Serum samples were utilized for a microarray analysis of bovine miRNA. Comparative examination of miRNA expression levels between cattle afflicted with fat necrosis and healthy cattle unveiled notable variances in 24 miRNAs, such as bta-miR-26a, bta-miR-29a, bta-miR-30a-5p and bta-miR-181a. Upon conducting miRNA-mediated KEGG pathway analysis, several pathways including the prolactin signal pathway, insulin resistance, autophagy, the insulin-signaling pathway and the FoxO-signaling pathway were found to be significantly enriched in the calf affected by fat necrosis. As a result, this study potentially indicates a potential connection between fat necrosis and diabetes in Korean native cattle.