Pnliprp1, pancreatic lipase-related protein 1, is a gene with a role in fat digestion as a triglyceride lipase inhibitor [2,3]. It may be involved in lipid metabolism-related pathways. Its biological importance lies in its potential impact on metabolic processes and exocrine pancreatic function [1]. Genetic models, such as gene knockout (KO) mouse models, can be valuable for studying its function.

In human studies, PNLIPRP1 null variants are associated with elevated glycemia and LDL cholesterol. Mendelian randomization indicates that type 2 diabetes (T2D) causes PNLIPRP1 hypermethylation, which in turn causes an increase in LDL cholesterol. In rat exocrine cell analyses, Pnliprp1 knockdown induces acinar-to-ductal metaplasia, a pre-pancreatic cancer state, and increases cholesterol levels, which can be reversed by statin [1]. Also, in the context of diet, its loss in some species is associated with low-fat intake, suggesting a beneficial role in fat-poor ecological niches [2].

In conclusion, Pnliprp1 is crucial in lipid metabolism and exocrine pancreatic function. Findings from genetic-model-based research, like the association between its null variants and metabolic changes, highlight its importance in T2D and cholesterol metabolism, as well as its potential implications in pancreatic diseases [1].

References:

1. Maurin, Lucas, Marselli, Lorella, Boissel, Mathilde, Froguel, Philippe, Khamis, Amna. . PNLIPRP1 Hypermethylation in Exocrine Pancreas Links Type 2 Diabetes and Cholesterol Metabolism. In Diabetes, 73, 1908-1918. doi:10.2337/db24-0215. https://pubmed.ncbi.nlm.nih.gov/39137110/

2. Wagner, Franziska, Ruf, Irina, Lehmann, Thomas, Stefen, Clara, Stuckas, Heiko. 2022. Reconstruction of evolutionary changes in fat and toxin consumption reveals associations with gene losses in mammals: A case study for the lipase inhibitor PNLIPRP1 and the xenobiotic receptor NR1I3. In Journal of evolutionary biology, 35, 225-239. doi:10.1111/jeb.13970. https://pubmed.ncbi.nlm.nih.gov/34882899/

3. Hecker, Nikolai, Sharma, Virag, Hiller, Michael. 2019. Convergent gene losses illuminate metabolic and physiological changes in herbivores and carnivores. In Proceedings of the National Academy of Sciences of the United States of America, 116, 3036-3041. doi:10.1073/pnas.1818504116. https://pubmed.ncbi.nlm.nih.gov/30718421/