title: Pancreatic lipase-related protein-2 (PLRP2) can contribute to dietary fat digestion in human newborns.
abstract: In newborn mice, PLRP2 is essential for fat digestion. In human infants, the role of PLRP2 in fat digestion is unclear, as it has poor activity against long-chain triglycerides in vitro. Also, many infants carry a genetic polymorphism resulting in a truncated protein, PLRP2 W340X, which may impact function significantly. We re-examined the properties of recombinant human PLRP2 and studied the impact of W340X mutation on its function. In the presence of bile salt micelles and colipase, human PLRP2 hydrolyzed long-chain tri-, di-, and monoglycerides. It hydrolyzed triolein at a level much lower than that of pancreatic triglyceride lipase, but close to that of carboxyl ester lipase, after a long lag phase, which could be eliminated by the addition of oleic acids. Human PLRP2 W340X was poorly secreted and largely retained inside the cell. The retention of the mutant protein triggered endoplasmic reticulum stress and unfolded protein responses. Our results show that earlier studies underestimated human PLRP2 activity against triolein by employing suboptimal assay conditions. In vivo, dietary fat emulsions contain fatty acids as a result of the action of gastric lipase. Consequently, PLRP2 can contribute to fat digestion during early infancy. Furthermore, infants with homozygous W340X alleles will not secrete functional PLRP2 and may have inefficient dietary fat digestion, particularly when breastfeeding is unavailable. Additionally, the aberrant folding of W340X mutant may cause chronic cellular stress and increase susceptibility of pancreatic exocrine cells to other metabolic stressors.
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh at University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15224, USA.
authors.forename: Xunjun
authors.initials: X
authors.lastname: Xiao
authors.forename: Amitava
authors.initials: A
authors.lastname: Mukherjee
authors.forename: Leah E
authors.initials: LE
authors.lastname: Ross
authors.forename: Mark E
authors.initials: ME
authors.lastname: Lowe
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D004041:Dietary Fats / Q000378:metabolism*; D004063:Digestion / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D006868:Hydrolysis; D007231:Infant, Newborn; D008049:Lipase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008823:Micelles; D020125:Mutation, Missense; D046790:Pancreas, Exocrine / Q000378:metabolism; D011110:Polymorphism, Genetic; D017510:Protein Folding; D011817:Rabbits; D056811:Unfolded Protein Response / Q000235:genetics
chemical_list: D001647:Bile Acids and Salts; D004041:Dietary Fats; D008823:Micelles; D008049:Lipase; C075988:pancreatic lipase related protein 2