Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Circulatory miRNAs as Correlates of Elevated Pancreatic Fat in a Mixed Ethnic Female Cohort from the TOFI_Asia Study

Version 1 : Received: 7 August 2023 / Approved: 8 August 2023 / Online: 8 August 2023 (05:26:46 CEST)

A peer-reviewed article of this Preprint also exists.

Ramzan, F.; Sequeira-Bisson, I.R.; Lu, L.W.; Mitchell, C.J.; D’Souza, R.F.; Vickers, M.H.; Poppitt, S.D.; Cameron-Smith, D. Circulatory miRNAs as Correlates of Elevated Intra-Pancreatic Fat Deposition in a Mixed Ethnic Female Cohort: The TOFI_Asia Study. Int. J. Mol. Sci. 2023, 24, 14393. Ramzan, F.; Sequeira-Bisson, I.R.; Lu, L.W.; Mitchell, C.J.; D’Souza, R.F.; Vickers, M.H.; Poppitt, S.D.; Cameron-Smith, D. Circulatory miRNAs as Correlates of Elevated Intra-Pancreatic Fat Deposition in a Mixed Ethnic Female Cohort: The TOFI_Asia Study. Int. J. Mol. Sci. 2023, 24, 14393.

Abstract

Aim: Ectopic lipid accumulation, including pancreatic steatosis, exacerbates type 2 diabetes risk in susceptible individuals. Dysregulated circulating microRNAs (miRNAs) have been identified to correlate with clinical measures of pancreatitis, pancreatic cancer, and type 1 diabetes. The aim of the current study was, therefore, to examine the association between circulating abundances of candidate miRNAs and pancreatic and liver fat deposition as quantified using magnetic resonance imaging (MRI) and spectroscopy (MRS). Methods: Asian Chinese (n=34; BMI=26.7±4.2 kg/m2) and European Caucasian (n=34; BMI=28.0±4.5 kg/m2) females from the TOFI_Asia cohort underwent MRI and MRS analysis of pancreas (MR-%pancreas) and liver (MR-%liver fat) respectively to quantify ectopic lipid deposition. Plasma miRNA abundances of a subset of circulatory miRNAs associated with pancreatic and liver steatosis were quantified by qRT-PCR. Results: miR-21-3p and miR-320a-5p correlated with MR-%pancreas fat, plasma insulin and HOMA2-IR but not MR-%liver fat. MR-%pancreas fat remained associated with decreasing miR-21-3p abundance following multivariate regression analysis. Conclusions: miR-21-3p and miR-320a were demonstrated to be negatively correlated with MR-%pancreas fat, independent of ethnicity. For miR-21-3p, this relationship persists with the inclusion of MR-%liver fat in the model, suggesting the potential for wider application as a specific circulatory correlate of pancreatic steatosis.

Keywords

miRNA; miR-21-3p; miR-320a-5p; ectopic; steatosis; biomarker; pancreas; liver

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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