Pancreatic steatosis: harbinger of type 2 diabetes in obese rodents.
OBJECTIVE
The aim of this study was to determine if the fat accumulation in the exocrine pancreas fat of obese Zucker diabetic fatty (ZDF) rodents, like that in their endocrine pancreas, precedes the onset of type 2 diabetes mellitus (T2DM). As the fat content of whole pancreas, but not islets, can now be measured in humans by magnetic resonance spectroscopy (MRS), such measurements could be used as a predictor of impending T2DM and an indication for preventive intervention.


METHODS
Obese ZDF (fa/fa) rats and lean (+/+) controls on a 6% fat diet were killed at time points from 6 to 16 weeks and total pancreatic fat was measured biochemically and electronmicroscopic examination of tissue for fat droplets was carried out.


RESULTS
Compared to lean ZDF controls, pancreatic fat was elevated above lean controls from 6 to 16 weeks of age, peaking at 10 weeks of age when hyperglycemia first appeared. The pancreatic profile of fat content in whole pancreas paralleled that of islets. Electronmicroscopic examination identified the acinar location of the fat droplets and ruled out a major contribution of intrapancreatic adipocytes.


CONCLUSIONS
The almost identical pattern of triglyceride overaccumulation in the exocrine and endocrine pancreas of obese rodents before the onset of T2DM suggests that MRS of the human pancreas might predict T2DM in obese subjects and permit timely interventions to prevent the disease.
Lee
Y
Y
Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Lingvay
I
I
Szczepaniak
L S
LS
Ravazzola
M
M
Orci
L
L
Unger
R H
RH
D050154:Adiposity; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D010179:Pancreas / Q000473:pathology; D010182:Pancreatic Diseases / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011924:Rats, Zucker; D014280:Triglycerides / Q000378:metabolism*
D014280:Triglycerides