Dietary fatty acids promote lipid droplet diversity through seipin enrichment in an ER subdomain

Abstract

Exogenous metabolites from microbial and dietary origins have profound effects on host metabolism. Here, we report that a sub-population of lipid droplets (LDs), which are conserved organelles for fat storage, is defined by metabolite-modulated targeting of the C. elegans seipin ortholog, SEIP-1. Loss of SEIP-1 function reduces the size of a subset of LDs while over-expression of SEIP-1 has the opposite effect. Ultrastructural analysis reveals SEIP-1 enrichment in an endoplasmic reticulum (ER) subdomain, which co-purifies with LDs. Analyses of C. elegans and bacterial genetic mutants indicate a requirement of polyunsaturated fatty acids (PUFAs) and microbial cyclopropane fatty acids (CFAs) for SEIP-1 enrichment, as confirmed by dietary supplementation experiments. In mammalian cells, heterologously expressed SEIP-1 engages nascent lipid droplets and promotes their subsequent expansion in a conserved manner. Our results suggest that microbial and polyunsaturated fatty acids serve unexpected roles in regulating cellular fat storage by promoting LD diversity.

Nuclear receptor NHR-49 promotes peroxisome proliferation to compensate for aldehyde dehydrogenase deficiency inC. elegans

“…We used a suite of red fluorescent organelle markers to determine the subcellular localization of GFP::ALH-4. Specifically, mRuby::DGAT-2, ACS-22::tagRFP, and TOMM-20(N)::mRuby, tagRFP::peroxisomal targeting signal 1(PTS1) were used to label LDs, ER, mitochondria and peroxisomes, respectively (Cao et al, 2019;Xu et al, 2012). Live transgenic worms were observed using confocal microscopy.…”

Modular metabolite assembly inC. elegansdepends on carboxylesterases and formation of lysosome-related organelles

“…1a) 14 . In addition to the autofluorescent LROs, several other types of intestinal granules have been characterized in C. elegans , including lipid droplets 21 and lysosome-related organelles that are not glo-1 -dependent 22 .…”

Married at Birth: Regulation of Cellular Fat Metabolism by ER–Lipid Droplet Crosstalk

“…In yeast, the first phosphatase specific to PA was purified to near homogeneity in 1989 (Lin and Carman, 1989; Carman, 2019). This phosphatase (annotated as Pah1 in yeast) was subsequently cloned and characterized (Han et al., 2006).…”

“…The regulation of Pah1/lipin-1 activities is intriguing. In yeast, Pah1 is primarily inactivated by phosphorylation and activated by dephosphorylation (Carman, 2019). The selective phosphorylation excludes Pah1 from the membrane, impairs the catalytic activities of Pah1, or promotes Pah1 degradation (Carman, 2019).…”