Pancreatic ectopic fat is characterized by adipocyte infiltration and altered lipid composition.
OBJECTIVE
Sustained exposure to lipids is deleterious for pancreatic islet function. This could be mediated through increased pancreatic fat following increased dietary fat and in obesity, which has implications for the onset of type 2 diabetes. The aims of this study were to determine changes in extent and composition of pancreatic, hepatic, and visceral fat in mice fed a high-fat diet (HFD, 40% by weight) compared with a control diet (5% fat) of similar fatty acid composition, and to compare composition and extent of pancreatic fat in human type 2 diabetes.


METHODS
Mice were fed HFD for 3 or 15 weeks. Human postmortem pancreas was examined from subjects with type 2 diabetes (n = 9) and controls (n = 7). Tissue lipid content and composition were determined by gas chromatography and pancreatic adipocyte infiltration quantified by morphometry.


RESULTS
Pancreatic triacylglycerol (TG) content was 20x greater (P < 0.05) in HFD mice and there were more pancreatic perilipin-positive adipocytes compared with controls after 15 weeks. The proportions of 18:1n -9 and 18:2n -6 in pancreatic TG and the 20:4n -6/18:2n -6 ratio in phospholipids, were higher (both P < 0.05) after HFD compared with controls. Human pancreatic TG content was correlated with the proportion of pancreatic perilipin-positive adipocytes (r = 0.64, P < 0.05) and associated with unsaturated fatty acid enrichment (P < 0.05).


CONCLUSIONS
Adipocyte infiltration in pancreatic exocrine tissue is associated with high-fat feeding in mice and pancreatic TG content in humans. This alters the fatty acid milieu of the islet which could contribute to islet dysfunction.
Pinnick
Katherine E
KE
Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK.
Collins
Stephan C
SC
Londos
Constantine
C
Gauguier
Dominique
D
Clark
Anne
A
Fielding
Barbara A
BA
D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002352:Carrier Proteins; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D006801:Humans; D050152:Intra-Abdominal Fat / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D019787:Linoleic Acid / Q000008:administration & dosage / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010179:Pancreas / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism; D015854:Up-Regulation
D002352:Carrier Proteins; D005230:Fatty Acids, Nonesterified; D000070778:Perilipin-1; D010750:Phosphoproteins; D014280:Triglycerides; D019787:Linoleic Acid; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase