Abhishek Mathur

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 (Lepob) and 12 obese hyperleptinemic (Lepdb) 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.

IAP Society News

Abstracts of the Joint Meeting of the European Pancreatic Club (EPC) and the International Association of Pancreatology (IAP) Lodz, June 25–28, 2008 www.pancreasweb.com/abstracts/abstracts.asps of the Joint Meeting of the European Pancreatic Club (EPC) and the International Association of Pancreatology (IAP) Lodz, June 25–28, 2008 www.pancreasweb.com/abstracts/abstracts.asp

190. Obesity Potentiates the Growth and Dissemination of Pancreatic Cancer

Background. Obesity is an independent risk factor for pancreatic cancer development and progression, although the mechanisms underlying this association are completely unknown. The aim of the current study was to investigate the influence of obesity on pancreatic cancer growth using a novel in vivo model. Methods. Lean (C57BL/6J) and obese (Lep Db and Lep Ob ) mice were inoculated with murine pancreatic cancer cells (PAN02), and studied after 5 weeks of tumor growth. Tumor histology was evaluated by hematoxylin and eosin staining, cellular proliferation was assessed by 5-bromodeoxyuridine, and apoptosis was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay. Serum adiponectin, leptin, and insulin levels were assayed. Results. Obese mice developed larger tumors, and a significantly greater number of mice developed metastases; mortality was also greater in obese mice. Tumor apoptosis did not differ among strains, but tumors from both obese strains had greater proliferation relative to those growing in lean animals. Serum adiponectin concentration correlated negatively and serum insulin concentration correlated positively with tumor proliferation. Intratumoral adipocyte mass in tumors from both obese strains was significantly greater than that in tumors of lean mice. Conclusion. Data from this novel in vivo model suggest that the altered adipokine milieu and insulin resistance observed in obesity may lead directly to changes in tumor microenvironment, thereby promoting pancreatic cancer growth and dissemination.