Peroxisomal regulation of energy homeostasis: Effect on obesity and related metabolic disorders

Kleiboeker, Brian; Lodhi, Irfan J.

doi:10.1016/j.molmet.2022.101577

Cited by 31 publications

(36 citation statements)

References 150 publications

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“…Thus, cold-activated induction specifically of the longer (enzymatically active) Adtrp isoform shown here might enhance BAT function. Peroxisome derived lipids are required for brown fat-mediated thermogenesis through regulation of cold-induced mitochondrial fission (Kleiboeker & Lodhi, 2022). The cold-induced switch in the peroxisome lipid transfer protein Scp2 in favour of the longer (and enzymatically active) isoform (Fig.…”

Section: Discussionmentioning

confidence: 99%

Nanopore sequencing unveils the complexity of the cold-activated murine brown adipose tissue transcriptome

Engelhard

Khani

Derdak

et al. 2022

Preprint

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Alternative transcription increases transcriptome complexity by expression of multiple transcripts per gene and thus fine tunes cellular identity and function. Annotation and quantification of transcripts at complex loci using short-read sequencing is non-trivial. Recent long-read sequencing methods such as those from Oxford Nanopore Technologies (ONT) and Pacific Biosciences aim at overcoming these problems by sequencing full length transcripts. Activation of BAT thermogenesis involves major transcriptomic remodelling and positively affects metabolism via increased energy expenditure and endocrine factors. Here we comprehensively benchmark features of ONT long-read sequencing protocols compared to Illumina shortread sequencing assessing alignment characteristics, gene and transcript detection and quantification, differential gene and transcript expression, transcriptome reannotation and differential transcript usage (DTU). We find that ONT sequencing is superior to Illumina for transcriptome reassembly and reduces the risk of false-positive events due to the ability to unambiguously map reads to transcripts, at the expense of statistical power for calling differentially expressed features. We identified novel isoforms of genes undergoing DTU in cold-activated BAT including Cars2, Adtrp, Acsl5, Scp2, Aldoa and Pde4d, validated by RT-qPCR. Finally, we provide a reannotation of the murine iBAT transcriptome as a valuable resource for researchers interested in the molecular biology underlying the regulation of BAT.

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Section: Discussionmentioning

confidence: 99%

Nanopore sequencing unveils the complexity of the cold-activated murine brown adipose tissue transcriptome

Engelhard

Khani

Derdak

et al. 2022

Preprint

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“…132 Plasmalogens also provide an important link between peroxisomes and energy regulation. 133 Peroxisomes, the site of plasmalogen synthesis from long-chain omega 3 and 6 essential fatty acid precursors, provide critical support of mitochondria, notably protection against reactive oxygen species. 134 Decreased plasmalogen ether phospholipids and increased BCAA (discussed under Metabolome) were among the significant longitudinal changes in 31 metabolites recently implicated in immunometabolic dysregulation that presaged the development of type 2 diabetes over 10 years in the Nurses' Health Study.…”

Section: Phospholipidsmentioning

confidence: 99%

Next Generation, Modifiable Cardiometabolic Biomarkers: Mitochondrial Adaptation and Metabolic Resilience: A Scientific Statement From the American Heart Association

Mietus-Snyder,

Perak,

Cheng

et al. 2023

Circulation

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Cardiometabolic risk is increasing in prevalence across the life span with disproportionate ramifications for youth at socioeconomic disadvantage. Established risk factors and associated disease progression are harder to reverse as they become entrenched over time; if current trends are unchecked, the consequences for individual and societal wellness will become untenable. Interrelated root causes of ectopic adiposity and insulin resistance are understood but identified late in the trajectory of systemic metabolic dysregulation when traditional cardiometabolic risk factors cross current diagnostic thresholds of disease. Thus, children at cardiometabolic risk are often exposed to suboptimal metabolism over years before they present with clinical symptoms, at which point life-long reliance on pharmacotherapy may only mitigate but not reverse the risk. Leading-edge indicators are needed to detect the earliest departure from healthy metabolism, so that targeted, primordial, and primary prevention of cardiometabolic risk is possible. Better understanding of biomarkers that reflect the earliest transitions to dysmetabolism, beginning in utero, ideally biomarkers that are also mechanistic/causal and modifiable, is critically needed. This scientific statement explores emerging biomarkers of cardiometabolic risk across rapidly evolving and interrelated “omic” fields of research (the epigenome, microbiome, metabolome, lipidome, and inflammasome). Connections in each domain to mitochondrial function are identified that may mediate the favorable responses of each of the omic biomarkers featured to a heart-healthy lifestyle, notably to nutritional interventions. Fuller implementation of evidence-based nutrition must address environmental and socioeconomic disparities that can either facilitate or impede response to therapy.

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“…Finally, skeletal muscle lipidomic analyses revealed that the abundances of only a very small number of intramuscular lipid species (~3% of the 734 lipids analyzed) correlated significantly with both adipose tissue and muscle insulin sensitivity. The only lipid class that correlated (negatively) with both adipose tissue and muscle insulin sensitivity was the plasmenyl‐phosphatidylethanolamines, which are peroxisome‐derived ether lipids that are involved in mitochondrial dynamics and the cellular response to oxidative stress [5]. Somewhat unexpectedly [2], neither intramuscular diacylglycerols nor ceramides correlated with adipose tissue or muscle insulin sensitivity in this cohort.…”

Section: Figurementioning

confidence: 99%

Dysfunctional adipose tissue and skeletal muscle insulin resistance: Cause and effect or two sides of the same coin?

Petersen

Mittendorfer

2023

Obesity

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Peroxisomal regulation of energy homeostasis: Effect on obesity and related metabolic disorders

Cited by 31 publications

References 150 publications

Nanopore sequencing unveils the complexity of the cold-activated murine brown adipose tissue transcriptome

Nanopore sequencing unveils the complexity of the cold-activated murine brown adipose tissue transcriptome

Next Generation, Modifiable Cardiometabolic Biomarkers: Mitochondrial Adaptation and Metabolic Resilience: A Scientific Statement From the American Heart Association

Dysfunctional adipose tissue and skeletal muscle insulin resistance: Cause and effect or two sides of the same coin?

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