Determination of tissue contributions to the circulating lipid pool in cold exposure via systematic assessment of lipid profiles

Jain, Raghav; Wade, Gina; Ong, Irene M.; Chaurasia, Bhagirath; Simcox, Judith

doi:10.1016/j.jlr.2022.100197

Cited by 23 publications

(26 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Changes in fatty acyl composition (number of carbons and degree of saturation) have been associated with differential response to metabolic stressors[28, 29]. Therefore, we evaluated the composition of the acyl chains in PC, PG, and CL lipids in WT and Abhd2 KO mice ( Figure S1C-E ).…”

Section: Resultsmentioning

confidence: 99%

Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/β hydrolase domain 2 (Abhd2) as an enzyme that metabolizes phosphatidylcholine and cardiolipin

Price

Stapleton

Schueler

et al. 2023

Preprint

View full text Add to dashboard Cite

We and others have previously shown that genetic association can be used to make causal connections between gene loci and small molecules measured by mass spectrometry in the bloodstream and in tissues. We identified a locus on mouse chromosome 7 where several phospholipids in liver showed strong genetic association to distinct gene loci. In this study, we integrated gene expression data with genetic association data to identify a single gene at the chromosome 7 locus as the driver of the phospholipid phenotypes. The gene encodes α/β-hydrolase domain 2 (Abhd2), one of 23 members of the ABHD gene family. We validated this observation by measuring lipids in a mouse with a whole-body deletion ofAbhd2. TheAbhd2KOmice had a significant increase in liver levels of phosphatidylcholine and phosphatidylethanolamine. Unexpectedly, we also found a decrease in two key mitochondrial lipids, cardiolipin and phosphatidylglycerol, in maleAbhd2KOmice. These data suggest that Abhd2 plays a role in the synthesis, turnover, or remodeling of liver phospholipids.

show abstract

Section: Resultsmentioning

confidence: 99%

Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/β hydrolase domain 2 (Abhd2) as an enzyme that metabolizes phosphatidylcholine and cardiolipin

Price

Stapleton

Schueler

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…LC-MS was performed for untargeted lipidomics of SHOW samples as previously described, with minor modifications (54). An Agilent (Santa Clara, CA, USA) 1290 Infinity II LC coupled to an Agilent 6546 quadrupole time-of-flight MS was used for analysis.…”

Section: Methodsmentioning

confidence: 99%

Identification of novel plasma lipid markers of cardiovascular disease risk in White and Black women

Jain

Davidson

Gonzalez

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Rationale: Cardiovascular disease (CVD) is the leading cause of mortality for women in the USA. Current clinical biomarkers are inadequate to determine CVD risk in women, especially Black women, who disproportionately suffer from CVD. Methods: Clinical data and LC-MS lipidomics from two independent study cohorts were used to identify novel circulating markers of CVD risk in White and Black women. Machine learning assessed predictive efficacy of identified lipids, and targeted oxylipid analysis provided insight into dysregulated inflammatory pathways. Results: Select phospholipids and triglycerides containing acyl chains in the arachidonic acid (ARA) pathway were predictive of systolic blood pressure (BP) after adjusting for biological factors including age, obesity, and glycemic status in White and Black women. Oxylipid levels indicated increased conversion of ARA through the COX and LOX enzymes to pro-inflammatory cytokines in Black women. Conclusion: ARA-containing phospholipid are independent predictors of CVD risk in White and Black women. Predisposition to CVD risk in Black women may further be explained by increased production of pro-inflammatory oxylipids relative to White women, regardless of blood pressure status. Future studies investigating the clinical utility of phospholipid ARA abundance as a marker of CVD risk in White and Black women are warranted.

show abstract

“…Left ventricular FS was calculated as: Heart Lipidomics. MTBE extraction will be performed with standards from SPLASH Lipidomix from Avanti, using methods outlined previously (Jain et al, 2022). Signal from the processed blank will be subtracted as background during data processing.…”

Section: In Vivo Proceduresmentioning

confidence: 99%

Late-life isoleucine restriction promotes physiological and molecular signatures of healthy aging

Yeh

Chini

Gallagher

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

A growing number of geroprotectors have demonstrated healthspan extension in young animals, but the effectiveness of these therapies when commenced in midlife or later has been under-studied. We and others have shown that much like calorie restriction (CR), restriction of specific nutrients, including total protein, the three branched-chain amino acids leucine, isoleucine, and valine, or isoleucine alone, can promote lifespan and metabolic health. While CR is less efficacious when starting in late life, the effects of interventions restricting amino acids in late life on healthy aging is unknown. Here, we investigate the metabolic, molecular, and physiological effects of consuming diets with a 67% reduction of either all amino acids (Low AA) or of isoleucine alone (Low Ile) in male and female C57BL/6J.Nia mice starting at 20 months of age. We find that both diets reduce adiposity in aged mice; however, these diets decreased lean mass, and did not show significant improvements in frailty or fitness. The glucose tolerance of both male and female mice consuming Low Ile and Low AA diets were improved. We also observed a moderate increase in energy expenditure and respiratory exchange ratio induced by the two dietary interventions. In the hearts of aged female mice, Low Ile reversed age-associated changes in heart rate and stroke volume, returning cardiac function to similar levels as observed in young mice. We found that both Low AA and Low Ile diets promoted a more youthful molecular cardiac profile, preventing age-dependent increases in phosphotidylglycerols. These results demonstrate that Low AA and Low Ile diets can improve aspects of metabolic health in aged mice of both sexes, and has positive effects on cardiac health in aged females, suggesting that these dietary interventions are translationally promising for promoting healthy aging even in older people.

show abstract

Determination of tissue contributions to the circulating lipid pool in cold exposure via systematic assessment of lipid profiles

Cited by 23 publications

References 56 publications

Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/β hydrolase domain 2 (Abhd2) as an enzyme that metabolizes phosphatidylcholine and cardiolipin

Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/β hydrolase domain 2 (Abhd2) as an enzyme that metabolizes phosphatidylcholine and cardiolipin

Identification of novel plasma lipid markers of cardiovascular disease risk in White and Black women

Late-life isoleucine restriction promotes physiological and molecular signatures of healthy aging

Contact Info

Product

Resources

About