Multi-generational effects of enrofloxacin on lifespan and reproduction of Caenorhabditis elegans with SKN-1-mediated antioxidant responses and lipid metabolism disturbances

Abstract Objectives Lipolysis is the catabolic process that hydrolyzes triglyceride (TG) to free fatty acids (FFAs) and glycerol under negative energy balance such as fasting. In adipocytes, adipose TG lipase (ATGL), hormone-sensitive lipase (HSL), and monoglyceride lipase play key roles in a series of TG hydrolysis reactions in mammals. However, overly activated adipose lipolysis is believed to contribute to link between obesity and systemic inflammation and oxidative stress. We previously demonstrated that piceatannol (PIC), a natural resveratrol analogue, inhibits adipogenesis in cultured adipocytes and lipogenesis in Caenorhabditis elegans. Furthermore, we showed that PIC extends the lifespan of C. elegans via the insulin/IGF-1 signaling. However, the effects of PIC on lipid metabolism during fasting state is unknown. Methods We conducted Oil-Red-O assay, Enzyme assay (TG and Free glycerol contents), PCR analysis and lifespan assay. Results In this study, we demonstrated that PIC-treated C. elegans exhibited suppressed lipolysis under fasting as judged by increased lipid accumulation and TG levels with decreased free glycerol level. Consistent with these findings, PIC treatment resulted in decreased mRNA levels of genes involved lipolysis such as atgl-1, hosl-1 and aak-2 in fasted C. elegans. Also, PIC treatment augmented fasting-induced lifespan of C. elegans by an increased daf-16 gene expression. However, such effect was abolished when atgl-1, aak-2, and daf-16 mutants were treated with PIC. In addition, we also found that autophagy is required for PIC-induced lifespan in C. elegans during fasting since autophagy inhibitor treatments and autophagy gene deficient worms resulted in blunting the lifespan extension effect of PIC. Conclusions Collectively, our results indicate that PIC contributes to lifespan extension in C. elegans during fasting possibly through regulating lipolysis- and/or autophagy-dependent lipid metabolism. Funding Sources 1. The National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2019R1A2C1086146) and (2019R1A6A3A03033878) 2. The Rural Development Administration of the Republic of Korea.

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Astragaloside IV Extends Lifespan of Caenorhabditis elegans by Improving Age-Related Functional Declines and Triggering Antioxidant Responses

Rejuvenation Research ◽

10.1089/rej.2020.2312 ◽

2020 ◽

Author(s):

Jianqin Zhang ◽

Xiaoli Xue ◽

Yuqi Qiao ◽

Daqi Li ◽

Qing Wei ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Astragaloside Iv ◽

Antioxidant Responses ◽

Age Related

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A conserved family of proteins facilitates nascent lipid droplet budding from the ER

The Journal of Cell Biology ◽

10.1083/jcb.201505067 ◽

2015 ◽

Vol 211 (2) ◽

pp. 261-271 ◽

Cited By ~ 137

Author(s):

Vineet Choudhary ◽

Namrata Ojha ◽

Andy Golden ◽

William A. Prinz

Keyword(s):

Electron Microscopy ◽

Endoplasmic Reticulum ◽

Lipid Metabolism ◽

Caenorhabditis Elegans ◽

Lipid Droplet ◽

Lipid Droplets ◽

De Novo ◽

Fat Storage ◽

Higher Eukaryotes ◽

Er Membrane

Lipid droplets (LDs) are found in all cells and play critical roles in lipid metabolism. De novo LD biogenesis occurs in the endoplasmic reticulum (ER) but is not well understood. We imaged early stages of LD biogenesis using electron microscopy and found that nascent LDs form lens-like structures that are in the ER membrane, raising the question of how these nascent LDs bud from the ER as they grow. We found that a conserved family of proteins, fat storage-inducing transmembrane (FIT) proteins, is required for proper budding of LDs from the ER. Elimination or reduction of FIT proteins in yeast and higher eukaryotes causes LDs to remain in the ER membrane. Deletion of the single FIT protein in Caenorhabditis elegans is lethal, suggesting that LD budding is an essential process in this organism. Our findings indicated that FIT proteins are necessary to promote budding of nascent LDs from the ER.

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Bisphenol S increases the obesogenic effects of a high-glucose diet through regulating lipid metabolism in Caenorhabditis elegans

Food Chemistry ◽

10.1016/j.foodchem.2020.127813 ◽

2021 ◽

Vol 339 ◽

pp. 127813

Author(s):

Xiang Xiao ◽

Xiaowei Zhang ◽

Juan Bai ◽

Jie Li ◽

Caiqin Zhang ◽

...

Keyword(s):

Lipid Metabolism ◽

Caenorhabditis Elegans ◽

High Glucose ◽

Bisphenol S

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Inter-generational consequences for growing Caenorhabditis elegans in liquid

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2018.0125 ◽

2019 ◽

Vol 374 (1770) ◽

pp. 20180125 ◽

Cited By ~ 6

Author(s):

Itamar Lev ◽

Roberta Bril ◽

Yunan Liu ◽

Lucila Inés Ceré ◽

Oded Rechavi

Keyword(s):

Caenorhabditis Elegans ◽

Early Life ◽

Epigenetic Inheritance ◽

Evolutionary Medicine ◽

C Elegans ◽

Generational Effects ◽

Large Populations ◽

Two Generations ◽

Generational Changes ◽

In The Wild

In recent years, studies in Caenorhabditis elegans nematodes have shown that different stresses can generate multigenerational changes. Here, we show that worms that grow in liquid media, and also their plate-grown progeny, are different from worms whose ancestors were grown on plates. It has been suggested that C. elegans might encounter liquid environments in nature, although actual observations in the wild are few and far between. By contrast, in the laboratory, growing worms in liquid is commonplace, and often used as an alternative to growing worms on agar plates, to control the composition of the worms' diet, to starve (and synchronize) worms or to grow large populations for biochemical assays. We found that plate-grown descendants of M9 liquid medium-grown worms were longer than control worms, and the heritable effects were already apparent very early in development. We tested for the involvement of different known epigenetic inheritance mechanisms, but could not find a single mutant in which these inter-generational effects are cancelled. While we found that growing in liquid always leads to inter-generational changes in the worms’ size, trans-generational effects were found to be variable, and in some cases, the effects were gone after one to two generations. These results demonstrate that standard cultivation conditions in early life can dramatically change the worms' physiology in adulthood, and can also affect the next generations. This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.

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