Abstract
Several publications have described biological roles for human patatin-like phospholipases (PNPLAs) in the regulation of adipocyte differentiation. Here, we report on the characterization and expression profiling of 10 human PNPLAs. A variety of bioinformatics approaches were used to identify and characterize all PNPLAs encoded by the human genome. The genes described represent a divergent family, most with a highly conserved ortholog in several mammalian species. In silico characterization predicts that two of the genes function as integral membrane proteins and are regulated by cAMP/cGMP. A structurally guided protein alignment of the patatin-like domain identifies a number of conserved residues in all family members. Quantitative PCR was used to determine the expression profile of each family member. Affymetrix-based profiling of a human preadipocyte cell line identified several members that are differentially regulated during cell differentiation. Cumulative data suggest that patatin-like genes normally expressed at very low levels are induced in response to environmental signals. Given the observed conservation of the patatin fold and lipase motif in all human PNPLAs, a single nomenclature to describe the PNPLA family is proposed.
Highlights
Several publications have described biological roles for human patatin-like phospholipases (PNPLAs) in the regulation of adipocyte differentiation
Recent studies investigating the role of the hormonesensitive lipase in mammalian adipose tissue identified a novel patatin-like lipase (TTS -2.2) that was significantly upregulated in differentiating murine adipocytes and appeared to act coordinately with hormone-sensitive lipase in the catabolism of triglycerides (10)
BLAST alignments indicated that both sequences are most homologous to intracellular membrane-associated calcium-independent phospholipase A2g
Summary
Several publications have described biological roles for human patatin-like phospholipases (PNPLAs) in the regulation of adipocyte differentiation. Proteins encoding a patatin-like domain are ubiquitously distributed across all life forms, including eukaryotes and prokaryotes [see the species distribution tree of the PFAM (protein family) database (4), accession number PF01734 (http://www.sanger.ac.uk//cgi-bin/Pfam/getacc?PF01734), for further details], and are observed to participate in a miscellany of biological roles, including sepsis induction (5), host colonization (6), triglyceride metabolism (7), and membrane trafficking (8). Of interest is the observation that prokaryotic patatin-like proteins appear more similar to eukaryotic paralogues than any other bacterial lipases (9) This suggests that distant homologs may have arisen from a common ancestor. Recent studies investigating the role of the hormonesensitive lipase in mammalian adipose tissue identified a novel patatin-like lipase (TTS -2.2) that was significantly upregulated in differentiating murine adipocytes and appeared to act coordinately with hormone-sensitive lipase in the catabolism of triglycerides (10). This article is available online at http://www.jlr.org except for ADPN, overexpression of the ADPN-like proteins resulted in decreased intracellular triglyceride levels (13)
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