Endocrine Abstracts

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) susceptibility varies among people due to its multifactorial nature. We hypothesised that we could induce insulin resistance and steatosis in a fatty breed of pig exposed to short-term high fat feeding. Female Mangalitza pigs (a fatty, slow growing breed) (n = 6) were metabolically phenotyped at baseline and during 15-weeks of high fat diet (HFD, 23% saturated fat). Insulin, glucose, NEFA, total cholesterol, liver enzymes and non-invasive blood pressure (NIBP) were monitored. Oral Glucose Tolerance Tests (OGTTs) were performed at baseline, week 7, and week 13. Liver biopsies and MRI were performed at baseline and week15. The HFD significantly increased body fat mass in MRI (from 27±6 to 41±6%) and weight (from 64±6 to106±6 kg). This was accompanied by greater, though not sustained, insulin secretion during OGTT (AUC_INS baseline 1075±563.5 vs. week13 3372±1835; P < 0.05), which effectively suppressed NEFA. Fasted NEFA initially increased (Baseline:501.5±176.7nmol/l vs. Week 6:1133±366.4nmol/l; P < 0.05) before returning to baseline levels (Week15:483.1±127nmol/l). Crucially, triglycerides, total cholesterol, liver enzymes, NIBP, and HOMA-IR remained unchanged throughout the trial. Liver histopathology, however, revealed early signs of pathology, including increased inflammation and ballooning (H&E, MASLD score 1.5IQR1.5 vs 4IQR1.92, P < 0.05), collagen deposition (Picrosirius Red, N of pixels 167.91x109 ± 86.25x109 vs 241.17x109±48.88x109,P < 0.05), and small lipid droplets (Oil Red O, droplets total area and number), though clinical steatosis did not develop. These pigs became obese yet demonstrated a positive adaptive response to HFD. They were not dyslipidaemic, nor did they develop severe insulin resistance or hypertension, suggesting a resilient phenotype where systemic metabolic health was maintained despite obesity. Liver histopathology, conversely, revealed a subclinical MASLD, suggesting that in this model, liver changes may develop at an early stage, preceding systemic pathology, which could allow to find the earliest drivers of MASLD.