Oleic Acid Metabolism in Response to Glucose in .

A key response to glucose stress is an increased production of unsaturated fatty acids to balance the increase in saturated fatty acids in the membrane. The homolog of stearoyl-CoA desaturase, FAT-7, introduces the first double bond into saturated C18 fatty acids yielding oleic acid, and is a critical regulatory point for surviving cold and glucose stress. Here, we incorporated C stable isotopes into the diet of nematodes and quantified the C-labelled fatty acid using GC-MS and HPLC/MS-MS to track its metabolic response to various concentrations of glucose.

Defining the glucosylceramide population of .

Glucosylceramides (GlcCer) are lipids that impact signaling pathways, serve as critical components of cellular membranes, and act as precursors for hundreds of other complex glycolipid species. Abnormal GlcCer metabolism is linked to many diseases, including cancers, diabetes, Gaucher disease, neurological disorders, and skin disorders. A key hurdle to fully understanding the role of GlcCer in disease is the development of methods to accurately detect and quantify these lipid species in a model organism.

Targeted lipidomics reveals a novel role for glucosylceramides in glucose response.

The addition of excess glucose to the diet drives a coordinated response of lipid metabolism pathways to tune the membrane composition to the altered diet. Here, we have employed targeted lipidomic approaches to quantify the specific changes in the phospholipid and sphingolipid populations that occur in elevated glucose conditions. The lipids within wild-type Caenorhabditis elegans are strikingly stable with no significant changes identified in our global mass spectrometry-based analysis.

Monomethyl branched-chain fatty acids are critical for Caenorhabitis elegans survival in elevated glucose conditions.

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.

Using stable isotope tracers to monitor membrane dynamics in C. elegans.

Membranes within an animal are composed of phospholipids, cholesterol, and proteins that together form a dynamic barrier. The types of lipids that are found within a membrane bilayer impact its biophysical properties including its fluidity, permeability, and susceptibility to damage. While membrane composition is very stable in healthy adults, aberrant membrane structure is seen in a wide and varied array of diseases as well as during natural aging.

Independent regulation of age associated fat accumulation and longevity.

Age-dependent changes in metabolism can manifest as cellular lipid accumulation, but how this accumulation is regulated or impacts longevity is poorly understood. We find that Saccharomyces cerevisiae accumulate lipid droplets (LDs) during aging. We also find that over-expressing BNA2, the first Biosynthesis of NAD (kynurenine) pathway gene, reduces LD accumulation during aging and extends lifespan.

Transaldolase inhibition impairs mitochondrial respiration and induces a starvation-like longevity response in Caenorhabditis elegans.

Mitochondrial dysfunction can increase oxidative stress and extend lifespan in Caenorhabditis elegans. Homeostatic mechanisms exist to cope with disruptions to mitochondrial function that promote cellular health and organismal longevity. Previously, we determined that decreased expression of the cytosolic pentose phosphate pathway (PPP) enzyme transaldolase activates the mitochondrial unfolded protein response (UPRmt) and extends lifespan.

HPLC-Based Mass Spectrometry Characterizes the Phospholipid Alterations in Ether-Linked Lipid Deficiency Models Following Oxidative Stress.

Despite the fact that the discovery of ether-linked phospholipids occurred nearly a century ago, many unanswered questions remain concerning these unique lipids. Here, we characterize the ether-linked lipids of the nematode with HPLC-MS/MS and find that more than half of the phosphoethanolamine-containing lipids are ether-linked, a distribution similar to that found in mammalian membranes. To explore the biological role of ether lipids in vivo, we target fatty acyl-CoA reductase (fard-1), an essential enzyme in ether lipid synthesis, with two distinct RNAi strategies.

Correction: DAF-16 and TCER-1 Facilitate Adaptation to Germline Loss by Restoring Lipid Homeostasis and Repressing Reproductive Physiology in C. elegans.

[This corrects the article DOI: 10.1371/journal.pgen.

DAF-16 and TCER-1 Facilitate Adaptation to Germline Loss by Restoring Lipid Homeostasis and Repressing Reproductive Physiology in C. elegans.

Elimination of the proliferating germline extends lifespan in C. elegans. This phenomenon provides a unique platform to understand how complex metazoans retain metabolic homeostasis when challenged with major physiological perturbations.

13C- and 15N-Labeling Strategies Combined with Mass Spectrometry Comprehensively Quantify Phospholipid Dynamics in C. elegans.

Membranes define cellular and organelle boundaries, a function that is critical to all living systems. Like other biomolecules, membrane lipids are dynamically maintained, but current methods are extremely limited for monitoring lipid dynamics in living animals. We developed novel strategies in C.

Rho signaling participates in membrane fluidity homeostasis.

Preservation of both the integrity and fluidity of biological membranes is a critical cellular homeostatic function. Signaling pathways that govern lipid bilayer fluidity have long been known in bacteria, yet no such pathways have been identified in eukaryotes. Here we identify mutants of the yeast Saccharomyces cerevisiae whose growth is differentially influenced by its two principal unsaturated fatty acids, oleic and palmitoleic acid.

Myc-dependent mitochondrial generation of acetyl-CoA contributes to fatty acid biosynthesis and histone acetylation during cell cycle entry.

Cell reprogramming from a quiescent to proliferative state requires coordinate activation of multiple -omic networks. These networks activate histones, increase cellular bioenergetics and the synthesis of macromolecules required for cell proliferation. However, mechanisms that coordinate the regulation of these interconnected networks are not fully understood.