Contribution of sams-1 and pmt-1 to lipid homoeostasis in adult Caenorhabditis elegans

Abstract

Accumulation of lipids inside the cell is primarily caused by disorders of lipid metabolism. S-adenosylmethionine synthetase (SAMS) produces SAM, an important methyl donor in various phospholipid methyltransferase reactions catalysed by phosphoethanolamine N-methyltransferase (PMT-1). A gel-based, quantitative proteomic analysis of the RNA interference (RNAi)-mediated inactivation of the pod-2 gene, which encodes acetyl-CoA carboxylase, showed a substantial down-regulation of SAMS-1. Consequently, RNAi of either sams-1 or pmt-1 caused a significant increase in lipid droplet size in the intestine of Caenorhabditis elegans. Lipid droplets exhibited increased triacylglycerol (TG) and decreased phosphatidylcholine (PC) levels, suggesting a reciprocal relationship between TG and PC regulation. These lipid-associated phenotypes were rescued by choline feeding. Among the five fat metabolism-related genes examined, two genes were highly induced by inactivation of sams-1 or pmt-1: pod-2 and stearoyl-CoA desaturase (fat-7). Thus, both SAMS-1 and PMT-1 were shown to contribute to the homoeostasis of TG and PC levels in C. elegans, which would provide an important survival strategy under harsh environmental conditions.

S-Adenosyl methionine synthetase 1 limits fat storage in Caenorhabditis elegans

“…This was also found by two other groups (Li et al 2011;Walker et al 2011). Accordingly, depletion of the respective SAM-dependent phosphoethanolamine methyltransferases reduces PC levels in other organisms as well (Brendza et al 2007;Li et al 2011;Palavalli et al 2006).…”

“…Asterisks indicate significant differences between WT worms and the respective sams-1 mutant at a given time point, determined using unpaired t tests with Welch's correction (*p \ 0.05; **p \ 0.01; ***p \ 0.001) larval stage to adulthood. Enlargement of LD in SAMS-1 deficient worms was recently described (Li et al 2011;Walker et al 2011). Worms passing through the L4 larvaeto-adult transition display dramatic germ cell proliferation, a marked extension of the gonadal arms, and gametogenesis, all of which are processes that consume large amounts of PC (Hubbard and Greenstein 2005).…”

“…The scale bar represents 50 lm in images a1/2, b1/2, and c1/2; 10 lm in images a3, b3, and c3; 2 lm in image d; 20 lm in e1/2 and f1/2; and 2 lm in images e3 and f3 enhanced expression of several lipogenic genes targeted by the transcription factor SBP-1, which is the C. elegans ortholog of mammalian SREBP-1. In studies in C. elegans, mice, and cell lines, deficiency of PEMT/PEAMT pathway enzymes has been shown to elevate TAG storage (Jacobs et al 2004;Walker et al 2011;Lu et al 2001;Li et al 2011). All of these findings are in accordance with the current hypothesis that decreasing PC levels directly activates SBP-1, which induces TAG synthesis (Walker et al 2011).…”

Cholesterol-Responsive Metabolic Proteins Are Required for Larval Development in Caenorhabditis elegans

“…This finding suggests that SAMS-1 and PMT-2 are not involved in sterol methylation because their levels were decreased in CS. It was also reported that SAMS-1 and PMT-1, another SAM-dependent methyltransferase, are down-regulated under stressful environmental condition and by pod-2 (acetylCoA carboxylase) RNAi (Li et al, 2011). Under these conditions, reduction of SAMS-1 and PMT-1 induced the accumulation of triacylglycerol lipid droplets in the intestine of worms (Li et al, 2011).…”

“…It was also reported that SAMS-1 and PMT-1, another SAM-dependent methyltransferase, are down-regulated under stressful environmental condition and by pod-2 (acetylCoA carboxylase) RNAi (Li et al, 2011). Under these conditions, reduction of SAMS-1 and PMT-1 induced the accumulation of triacylglycerol lipid droplets in the intestine of worms (Li et al, 2011). Therefore, in CS condition, reduction of SAMS-1 and PMT-2 might also alter lipid metabolism and this change of lipid metabolism might affect larval development.…”