Abstract

The maintenance of optimal membrane composition under basal and stress conditions is critical for the survival of an organism. High-glucose stress has been shown to perturb membrane properties by decreasing membrane fluidity, and the membrane sensor PAQR-2 is required to restore membrane integrity. However, the mechanisms required to respond to elevated dietary glucose are not fully established. In this study, we used a 13C stable isotope-enriched diet and mass spectrometry to better understand the impact of glucose on fatty acid dynamics in the membrane of Caenorhabditis elegans. We found a novel role for monomethyl branched-chain fatty acids (mmBCFAs) in mediating the ability of the nematodes to survive conditions of elevated dietary glucose. This requirement of mmBCFAs is unique to glucose stress and was not observed when the nematode was fed elevated dietary saturated fatty acid. In addition, when worms deficient in elo-5, the major biosynthesis enzyme of mmBCFAs, were fed Bacillus subtilis (a bacteria strain rich in mmBCFAs) in combination with high glucose, their survival rates were rescued to wild-type levels. Finally, the results suggest that mmBCFAs are part of the PAQR-2 signaling response during glucose stress. Taken together, we have identified a novel role for mmBCFAs in stress response in nematodes and have established these fatty acids as critical for adapting to elevated glucose.

Highlights

  • In many disease states, including diabetes, cancer, and neurodegenerative spectrometry to better understand the diseases, defects in membrane structure impact of glucose on fatty acid dynamics and composition have been identified (1)in the membrane of Caenorhabditis (2) (3) (4) (5) (6)

  • We found a novel role for are essential barriers between the monomethyl branched-chain fatty acids intracellular and extracellular in mediating the ability of environment and are crucial in the the nematodes to survive conditions of compartmentalization of subcellular elevated dietary glucose

  • While it has been established that high glucose diets require a compensatory metabolic shift in lipid pathways, the specific alterations in the membrane optimum membrane composition when lipids of animals exposed to excess challenged with glucose

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Summary

Introduction

In many disease states, including diabetes, cancer, and neurodegenerative spectrometry to better understand the diseases, defects in membrane structure impact of glucose on fatty acid dynamics and composition have been identified (1). We found a novel role for are essential barriers between the monomethyl branched-chain fatty acids intracellular and extracellular (mmBCFAs) in mediating the ability of environment and are crucial in the the nematodes to survive conditions of compartmentalization of subcellular elevated dietary glucose. In C. perturbations in the biophysical elegans, monomethyl branched-chain properties of the membrane and can fatty acids (mmBCFAs) are found within allow membranes to adapt to variations the membrane at significant in environmental cues including concentrations, accounting for about temperature and dietary composition.

They are synthesized from branchedchain amino acids particularly leucine
Quantifying membrane dynamics with elevated dietary glucose
Previous FRAP studies have shown that
We aimed to identify mechanisms that
We hypothesize that the high mortality
Altered Dietary Conditions
Viability Curves and Lifespans
Stable Isotope Labeling Strategy
Newly Incorporated Fatty Acids
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