Nuclear magnetic resonance spectroscopy-based metabolomics of the fatty pancreas: Implicating fat in pancreatic pathology

Background: Obesity is a worldwide epidemic and a significant risk factor for pancreatic diseases including pancreatitis and pancreatic cancer; the mechanisms underlying this association are unknown. Metabolomics is a powerful new analytical approach for describing the metabolome (compliment of small molecules) of cells, tissue or biofluids at any given time. Our aim was to analyze pancreatic fat content in lean and congenitally obese mice using both metabolomic analysis and conventional chromatography. Methods: The pancreatic fat content of 12 lean (C57BL/6J), 12 obese leptin-deficient (Lep^ob) and 12 obese hyperleptinemic (Lep^db) mice was evaluated by metabolomic analysis, thin-layer and gas chromatography. Results: Pancreata of congenitally obese mice had significantly more total pancreatic fat, triglycerides and free fatty acids, but significantly less phospholipids and cholesterol than those of lean mice. Metabolomic analysis showed excellent correlation with thin-layer and gas chromatography in measuring total fat, triglycerides and phospholipids. Conclusions: Differences in pancreatic fat content and character may have important implications when considering the local pancreatic proinflammatory milieu in obesity. Metabolomic analysis is a valid, powerful tool with which to further define the mechanisms by which fat impacts pancreatic disease.