title: Differential regulation of pancreatic digestive enzymes during chronic high-fat diet-induced obesity in C57BL/6J mice.
abstract: Exocrine pancreatic digestive enzymes are essential for the digestion of dietary components and are regulated by them. Chronic excess dietary high fat (HF) consumption is a contributing factor of diet-induced obesity (DIO) and associated chronic diseases and requires adaptation by the pancreas. The aim of the present study was to investigate the effects of chronic HF diet feeding on exocrine pancreatic digestive enzyme transcript levels in DIO C57BL/6J mice. C57BL/6J mice were fed diets containing either 10 or 45% energy (E%) derived from fat for 12 weeks (n 10 mice per diet group). Pancreatic tissue and blood samples were collected at 0, 4 and 12 weeks. The expression of a panel of exocrine pancreatic digestive enzymes was analysed using quantitative RT-PCR and Western blot analysis. The HF (45 E%) diet-fed C57BL/6J mice developed obesity, hyperleptinaemia, hyperglycaemia and hyperinsulinaemia. The transcript levels of pancreatic lipase (PL), pancreatic lipase-related protein 2 (PLRP2) and pancreatic phospholipase A2 (PLA2) were initially elevated; however, they were down-regulated to basal control levels at week 12. The transcript levels of colipase were significantly affected by diet and time. The protein levels of PL and PLRP2 responded to HF diet feeding. The transcript levels of amylase and proteases were not significantly affected by diet and time. The transcript levels of specific lipases in hyperinsulinaemic, hyperleptinaemic and hyperglycaemic DIO C57BL/6J mice are down-regulated. However, these mice compensate for this by the post-transcriptional regulation of the levels of proteins that respond to dietary fat. This suggests a complex regulatory mechanism involved in the modulation of fat digestion.
authors.affiliation: Department of Nutrition,Faculty of Health Sciences, Ariel University,Ariel40700,Israel.
authors.forename: Ruth Z
authors.initials: RZ
authors.lastname: Birk
authors.affiliation: Molecular Nutrition Unit, Research Center for Nutrition and Food Sciences, Technische Universität München,Freising-Weihenstephan,Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Rubio-Aliaga
authors.affiliation: Netherlands Nutrigenomics Centre, Top Institute Food and Nutrition,Wageningen,The Netherlands.
authors.forename: Mark V
authors.initials: MV
authors.lastname: Boekschoten
authors.affiliation: Department of Nutrition,Faculty of Health Sciences, Ariel University,Ariel40700,Israel.
authors.forename: Hila
authors.initials: H
authors.lastname: Danino
authors.affiliation: Netherlands Nutrigenomics Centre, Top Institute Food and Nutrition,Wageningen,The Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
authors.affiliation: Molecular Nutrition Unit, Research Center for Nutrition and Food Sciences, Technische Universität München,Freising-Weihenstephan,Germany.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Daniel
mesh_terms: D000818:Animals; D003089:Colipases / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D015971:Gene Expression Regulation, Enzymologic; D006943:Hyperglycemia / Q000209:etiology; D006946:Hyperinsulinism / Q000209:etiology; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000201:enzymology* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D046790:Pancreas, Exocrine / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology; D054497:Phospholipases A2, Secretory / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation
chemical_list: D003089:Colipases; D020738:Leptin; D012333:RNA, Messenger; D008049:Lipase; C075988:pancreatic lipase related protein 2; D054497:Phospholipases A2, Secretory