Intrapancreatic fat deposition is unrelated to liver steatosis in metabolic dysfunction-associated steatotic liver disease

Background & Aims: Individuals with obesity may develop intrapancreatic fat deposition (IPFD) and fatty pancreas disease (FPD). Whether this causes inflammation and fibrosis and leads to pancreatic dysfunction is less established than for liver damage in metabolic dysfunction-associated steatotic liver disease (MASLD). Moreover, the interrelations of FPD and MASLD are poorly understood. Therefore, we aimed to assess IPFD and fibro-inflammation in relation to pancreatic function and liver disease severity in individuals with MASLD. Methods: Seventy-six participants from the Amsterdam MASLD-MASH cohort (ANCHOR) study underwent liver biopsy and multiparametric MRI of the liver and pancreas, consisting of proton-density fat fraction sequences, T1 mapping and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). Results: The prevalence of FPD was 37.3%. There was a clear correlation between pancreatic T1 relaxation time, which indicates fibro-inflammation, and parameters of glycemic dysregulation, namely HbA1c (R = 0.59; p <0.001), fasting glucose (R = 0.51; p <0.001) and the presence of type 2 diabetes (mean 802.0 ms vs. 733.6 ms; p <0.05). In contrast, there was no relation between IPFD and hepatic fat content (R = 0.03; p = 0.80). Pancreatic IVIM diffusion (IVIM-D) was lower in advanced liver fibrosis (p <0.05) and pancreatic perfusion (IVIM-f), reflecting vessel density, inversely correlated to histological MASLD activity (p <0.05). Conclusions: Consistent relations exist between pancreatic fibro-inflammation on MRI and endocrine function in individuals with MASLD. However, despite shared dysmetabolic drivers, our study suggests IPFD is a separate pathophysiological process from MASLD. Impact and implications: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and 68% of people with type 2 diabetes have MASLD. However, fat infiltration and inflammation in the pancreas are understudied in individuals with MASLD. In this cross-sectional MRI study, we found no relationship between fat accumulation in the pancreas and liver in a cohort of patients with MASLD. However, our results show that inflammatory and fibrotic processes in the pancreas may be interrelated to features of type 2 diabetes and to the severity of liver disease in patients with MASLD. Overall, the results suggest that pancreatic endocrine dysfunction in individuals with MASLD may be more related to glucotoxicity than to lipotoxicity. Clinical trial number: NTR7191 (Dutch Trial Register).