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Perilipin-related protein regulates lipid metabolism in C. elegans.

Chughtai AA, Kaššák F, Kostrouchová M, Novotný JP, Krause MW, Saudek V, Kostrouch Z, Kostrouchová M - PeerJ (2015)

Bottom Line: Perilipins have been identified in organisms as diverse as metazoa, fungi, and amoebas but strikingly not in nematodes.In contrast to embryos, lipid-containing structures in enterocytes and in epidermal cells of adult animals are smaller in mutants than in wild type animals.Our results demonstrate the existence of a perilipin-related regulation of fat metabolism in nematodes and provide new possibilities for functional studies of lipid metabolism.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Cellular Biology and Pathology, First Faculty of Medicine, Charles University in Prague , Albertov, Prague , Czech Republic.

ABSTRACT
Perilipins are lipid droplet surface proteins that contribute to fat metabolism by controlling the access of lipids to lipolytic enzymes. Perilipins have been identified in organisms as diverse as metazoa, fungi, and amoebas but strikingly not in nematodes. Here we identify the protein encoded by the W01A8.1 gene in Caenorhabditis elegans as the closest homologue and likely orthologue of metazoan perilipin. We demonstrate that nematode W01A8.1 is a cytoplasmic protein residing on lipid droplets similarly as human perilipins 1 and 2. Downregulation or elimination of W01A8.1 affects the appearance of lipid droplets resulting in the formation of large lipid droplets localized around the dividing nucleus during the early zygotic divisions. Visualization of lipid containing structures by CARS microscopy in vivo showed that lipid-containing structures become gradually enlarged during oogenesis and relocate during the first zygotic division around the dividing nucleus. In mutant embryos, the lipid containing structures show defective intracellular distribution in subsequent embryonic divisions and become gradually smaller during further development. In contrast to embryos, lipid-containing structures in enterocytes and in epidermal cells of adult animals are smaller in mutants than in wild type animals. Our results demonstrate the existence of a perilipin-related regulation of fat metabolism in nematodes and provide new possibilities for functional studies of lipid metabolism.

No MeSH data available.


Related in: MedlinePlus

Enzymes and regulatory proteins involved in lipolysis (Adapted from Lass et al., 2011).Mammalian proteins are indicated above the arrows and their C. elegans orthologues (Lee et al., 2014) below. Triacylglycerol (TAG) is progressively hydrolysed to diacylglycerol (DAG), monoacylglycerol (MAG) and glycerol (G) by lipases specific for each of these steps: adipose triacylglycerol lipase (ATGL), hormone-sensitive lipase (HSL) and finally monoacylglycerol lipase (MGL). LID-1 and C37H5.3 were proposed to be orthologues of ABHD5/CGI58 in C. elegans (Lee et al., 2014; Xie & Roy, 2015). HSL also shows some activity in the first and third step. The access of ATGL and HSL to lipid droplets is regulated by perilipin, which is under the control of protein kinase A (PKA). W01A8.1 is proposed to be a perilipin orthologue in the present work.
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fig-7: Enzymes and regulatory proteins involved in lipolysis (Adapted from Lass et al., 2011).Mammalian proteins are indicated above the arrows and their C. elegans orthologues (Lee et al., 2014) below. Triacylglycerol (TAG) is progressively hydrolysed to diacylglycerol (DAG), monoacylglycerol (MAG) and glycerol (G) by lipases specific for each of these steps: adipose triacylglycerol lipase (ATGL), hormone-sensitive lipase (HSL) and finally monoacylglycerol lipase (MGL). LID-1 and C37H5.3 were proposed to be orthologues of ABHD5/CGI58 in C. elegans (Lee et al., 2014; Xie & Roy, 2015). HSL also shows some activity in the first and third step. The access of ATGL and HSL to lipid droplets is regulated by perilipin, which is under the control of protein kinase A (PKA). W01A8.1 is proposed to be a perilipin orthologue in the present work.

Mentions: Lipolysis is a tightly regulated cellular process in which triacylglycerol fatty acids (TAG) are degraded into free fatty acids (FFA) and glycerol (G) with intermediates of diacylglycerol (DAG) and monoacylglycerol (MAG). The function and regulation of three key lipases (adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and monoglyceride lipase (MGL) have been studied in great detail in mammalian adipocytes (reviewed in Lass et al., 2011). Multidomain and multifunctional LD coating proteins, the perilipins, mediate the access of ATGL and HSL to LDs. Briefly (Fig. 7), the phosphorylated N-terminal domain PAT in perilipin interacts with HSL and brings it in contact with lipid droplets (LDs) (Shen et al., 2009). At the same time, the C-terminal phosphorylation (controlled by the kinase PKA) releases a specific activator of ATGL named ABHD5 without which ATGL remains inactive in the cytoplasm. The final step of the glycolysis is catalyzed by MGL. Conversely, unphosphorylated perilipin blocks lipolysis in the basal fed state by blocking the access of lipolytic enzymes to the fat stored in LDs. Both HSL and ATGL are the rate-limiting enzymes needed for fatty acids mobilization (Schweiger et al., 2006). A variation of this regulatory process, although less well understood in detail, exists in other cells and organisms. Most organisms so far studied contain several perilipin genes, complicating the analysis of complete perilipin loss-of-function.


Perilipin-related protein regulates lipid metabolism in C. elegans.

Chughtai AA, Kaššák F, Kostrouchová M, Novotný JP, Krause MW, Saudek V, Kostrouch Z, Kostrouchová M - PeerJ (2015)

Enzymes and regulatory proteins involved in lipolysis (Adapted from Lass et al., 2011).Mammalian proteins are indicated above the arrows and their C. elegans orthologues (Lee et al., 2014) below. Triacylglycerol (TAG) is progressively hydrolysed to diacylglycerol (DAG), monoacylglycerol (MAG) and glycerol (G) by lipases specific for each of these steps: adipose triacylglycerol lipase (ATGL), hormone-sensitive lipase (HSL) and finally monoacylglycerol lipase (MGL). LID-1 and C37H5.3 were proposed to be orthologues of ABHD5/CGI58 in C. elegans (Lee et al., 2014; Xie & Roy, 2015). HSL also shows some activity in the first and third step. The access of ATGL and HSL to lipid droplets is regulated by perilipin, which is under the control of protein kinase A (PKA). W01A8.1 is proposed to be a perilipin orthologue in the present work.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562238&req=5

fig-7: Enzymes and regulatory proteins involved in lipolysis (Adapted from Lass et al., 2011).Mammalian proteins are indicated above the arrows and their C. elegans orthologues (Lee et al., 2014) below. Triacylglycerol (TAG) is progressively hydrolysed to diacylglycerol (DAG), monoacylglycerol (MAG) and glycerol (G) by lipases specific for each of these steps: adipose triacylglycerol lipase (ATGL), hormone-sensitive lipase (HSL) and finally monoacylglycerol lipase (MGL). LID-1 and C37H5.3 were proposed to be orthologues of ABHD5/CGI58 in C. elegans (Lee et al., 2014; Xie & Roy, 2015). HSL also shows some activity in the first and third step. The access of ATGL and HSL to lipid droplets is regulated by perilipin, which is under the control of protein kinase A (PKA). W01A8.1 is proposed to be a perilipin orthologue in the present work.
Mentions: Lipolysis is a tightly regulated cellular process in which triacylglycerol fatty acids (TAG) are degraded into free fatty acids (FFA) and glycerol (G) with intermediates of diacylglycerol (DAG) and monoacylglycerol (MAG). The function and regulation of three key lipases (adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and monoglyceride lipase (MGL) have been studied in great detail in mammalian adipocytes (reviewed in Lass et al., 2011). Multidomain and multifunctional LD coating proteins, the perilipins, mediate the access of ATGL and HSL to LDs. Briefly (Fig. 7), the phosphorylated N-terminal domain PAT in perilipin interacts with HSL and brings it in contact with lipid droplets (LDs) (Shen et al., 2009). At the same time, the C-terminal phosphorylation (controlled by the kinase PKA) releases a specific activator of ATGL named ABHD5 without which ATGL remains inactive in the cytoplasm. The final step of the glycolysis is catalyzed by MGL. Conversely, unphosphorylated perilipin blocks lipolysis in the basal fed state by blocking the access of lipolytic enzymes to the fat stored in LDs. Both HSL and ATGL are the rate-limiting enzymes needed for fatty acids mobilization (Schweiger et al., 2006). A variation of this regulatory process, although less well understood in detail, exists in other cells and organisms. Most organisms so far studied contain several perilipin genes, complicating the analysis of complete perilipin loss-of-function.

Bottom Line: Perilipins have been identified in organisms as diverse as metazoa, fungi, and amoebas but strikingly not in nematodes.In contrast to embryos, lipid-containing structures in enterocytes and in epidermal cells of adult animals are smaller in mutants than in wild type animals.Our results demonstrate the existence of a perilipin-related regulation of fat metabolism in nematodes and provide new possibilities for functional studies of lipid metabolism.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Cellular Biology and Pathology, First Faculty of Medicine, Charles University in Prague , Albertov, Prague , Czech Republic.

ABSTRACT
Perilipins are lipid droplet surface proteins that contribute to fat metabolism by controlling the access of lipids to lipolytic enzymes. Perilipins have been identified in organisms as diverse as metazoa, fungi, and amoebas but strikingly not in nematodes. Here we identify the protein encoded by the W01A8.1 gene in Caenorhabditis elegans as the closest homologue and likely orthologue of metazoan perilipin. We demonstrate that nematode W01A8.1 is a cytoplasmic protein residing on lipid droplets similarly as human perilipins 1 and 2. Downregulation or elimination of W01A8.1 affects the appearance of lipid droplets resulting in the formation of large lipid droplets localized around the dividing nucleus during the early zygotic divisions. Visualization of lipid containing structures by CARS microscopy in vivo showed that lipid-containing structures become gradually enlarged during oogenesis and relocate during the first zygotic division around the dividing nucleus. In mutant embryos, the lipid containing structures show defective intracellular distribution in subsequent embryonic divisions and become gradually smaller during further development. In contrast to embryos, lipid-containing structures in enterocytes and in epidermal cells of adult animals are smaller in mutants than in wild type animals. Our results demonstrate the existence of a perilipin-related regulation of fat metabolism in nematodes and provide new possibilities for functional studies of lipid metabolism.

No MeSH data available.


Related in: MedlinePlus