HLH-30 dependent rewiring of metabolism during starvation inC. elegans

Abstract

SummaryOne of the most fundamental challenges for all living organisms is to sense and respond to alternating nutritional conditions in order to adapt their metabolism and physiology to promote survival and achieve balanced growth. Here, we applied metabolomics and lipidomics to examine temporal regulation of metabolism during starvation in wildtype Caenorhabditis elegans and in animals lacking the transcription factor HLH-30. Our findings show for the first time that starvation alters the abundance of hundreds of metabolites and lipid species in a temporal- and HLH-30-dependent manner. We demonstrate that premature death of hlh-30 animals under starvation can be prevented by supplementation of exogenous fatty acids, and that HLH-30 is required for complete oxidation of long-chain fatty acids. We further show that RNAi-mediated knockdown of the gene encoding carnitine palmitoyl transferase I (cpt-1) only impairs survival of wildtype animals and not of hlh-30 animals. Strikingly, we also find that compromised generation of peroxisomes by prx-5 knockdown renders hlh-30 animals hypersensitive to starvation, which cannot be rescued by supplementation of exogenous fatty acids. Collectively, our observations show that mitochondrial functions are compromised in hlh-30 animals and that hlh-30 animals rewire their metabolism to largely depend on functional peroxisomes during starvation, underlining the importance of metabolic plasticity to maintain survival.Abstract Figure

Characterising Alzheimer's disease through integrative NMR- and LC-MS-based metabolomics

“…The samples were analysed as in Dall et al [ 31 ]. In brief, 5 μL was injected using a 400 μl/min and the following composition of eluent A (0.1% formic acid) and eluent B (0.1% formic acid, acetonitrile) solvents: 3% B from 0 to 1.5 min, 3%–40% B from 1.5 to 4.5 min, 40%–95% B from 4.5 to 7.5 min, 95% B from 7.5 to 10.1 min and 95%–3% B from 10.1 to 10.5 min before equilibration for 3.5 min with the initial conditions.…”

“…The flow from the UPLC was coupled to a Q Exactive HF mass spectrometer (Thermo Fisher Scientific) for mass spectrometric analysis in both positive and negative ion modes. The raw data were also processed as in Dall et al [ 31 ] using MZmine (v 2.53) [ 32 ].…”

High‐fat diet‐induced obesity augments the deleterious effects of estrogen deficiency on bone: Evidence from ovariectomized mice

“…The raw data were also processed as in Dall et al (2021) using MZmine (v 2.53; Pluskal et al, 2010). Features were annotated by searching against NIST17 Tandem Mass Spectral Library, MoNA – MassBank of North America library and finally SIRUIS (v. 4.7.0 [Duhrkop et al, 2019]).…”

“…The samples were overall analyzed as in Dall et al (2021). In brief, 5 μl was injected on a Vanquish Horizon UPLC (Thermo Fisher Scientific) where a flow of 400 μl/min was used with the following composition of eluent A (0.1% formic acid) and eluent B (0.1% formic acid, acetonitrile): 3% B from 0 to 1.5 min, 3% to 40% B from 1.5 to 3 min, 40% to 95% B from 3 to 5 min, 95% B from 5 to 7.6 min and 95% to 3% B from 7.6 to 8 min before equilibration for 3.5 min with the initial conditions.…”

Quo Vadis Caenorhabditis elegans Metabolomics—A Review of Current Methods and Applications to Explore Metabolism in the Nematode

“…Further analysis showed that hlh-30 mutants shift their metabolism from mitochondrial to peroxisomal beta-oxidation. Further knockdown of prx-5 , compromising the generation of peroxisomes, further rendered hlh-30 mutants hypersensitive to starvation [ 96 ].…”