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Single Nucleus Transcriptomics Identifies Separate Classes of UCP1 and Futile Cycle Adipocytes

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE184707 | GEO | 2024/07/30

REPOSITORIES: GEO

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Single Nucleus Transcriptomics Identifies Separate Classes of UCP1 and Futile Cycle Adipocytes [human snRNA-seq]

Project description:Adipose tissue can recruit catabolic adipocytes which utilize chemical energy to dissipate heat. This process occurs either by uncoupled respiration through uncoupling protein 1 (UCP1) or by utilizing ATP-dependent futile cycles (FCs). However, it remains unclear how these pathways coexist since both processes rely on the mitochondrial membrane potential. Utilizing single-nucleus RNA-sequencing to deconvolute the heterogeneity of subcutaneous adipose tissue in mice and humans, we identify at least 2 distinct subpopulations of beige adipocytes: FC-beige and UCP1-beige adipocytes. Importantly, we demonstrate that the FC-utilizing beige subpopulation is metabolically highly active and utilizes FCs to dissipate energy thus contributing to thermogenesis independent of UCP1. Furthermore, FC-beige adipocytes are important drivers of systemic energy homeostasis and linked to glucose metabolism and obesity resistance in humans. Taken together, our findings identify a noncanonical thermogenic adipocyte subpopulation, which could be an important regulator of energy homeostasis in mammals.

2024-07-30 | GSE184687 | GEO

Single Nucleus Transcriptomics Identifies Separate Classes of UCP1 and Futile Cycle Adipocytes [mouse snRNA-seq]

2024-07-30 | GSE184706 | GEO

Single Nucleus Transcriptomics Identifies Separate Classes of UCP1 and Futile Cycle Adipocytes [mouse snRNA-Seq Ucp1KO]

2024-07-30 | GSE270706 | GEO

Single Nucleus Transcriptomics Identifies Separate Classes of UCP1 and Futile Cycle Adipocytes

Project description:Single Nucleus Transcriptomics Identifies Separate Classes of UCP1 and Futile Cycle Adipocytes

| PRJNA765709 | ENA

Single Nucleus Transcriptomics Identifies Separate Classes of UCP1 and Futile Cycle Adipocytes [human snRNA-seq]

Project description:Single Nucleus Transcriptomics Identifies Separate Classes of UCP1 and Futile Cycle Adipocytes [human snRNA-seq]

| PRJNA765667 | ENA

Single Nucleus Transcriptomics Identifies Separate Classes of UCP1 and Futile Cycle Adipocytes [mouse snRNA-seq]

Project description:Single Nucleus Transcriptomics Identifies Separate Classes of UCP1 and Futile Cycle Adipocytes [mouse snRNA-seq]

| PRJNA765712 | ENA

Single Nucleus Transcriptomics Identifies Separate Classes of UCP1 and Futile Cycle Adipocytes [mouse snRNA-Seq Ucp1KO]

Project description:Single Nucleus Transcriptomics Identifies Separate Classes of UCP1 and Futile Cycle Adipocytes [mouse snRNA-Seq Ucp1KO]

| PRJNA1128056 | ENA

Mitochondrial Patch Clamp of Beige Adipocytes Reveals UCP1-Positive and UCP1-Negative Cells Both Exhibiting Futile Creatine Cycling.

Project description:Cold and other environmental factors induce "browning" of white fat depots-development of beige adipocytes with morphological and functional resemblance to brown fat. Similar to brown fat, beige adipocytes are assumed to express mitochondrial uncoupling protein 1 (UCP1) and are thermogenic due to the UCP1-mediated H+ leak across the inner mitochondrial membrane. However, this assumption has never been tested directly. Herein we patch clamped the inner mitochondrial membrane of beige and brown fat to provide a direct comparison of their thermogenic H+ leak (IH). All inguinal beige adipocytes had robust UCP1-dependent IH comparable to brown fat, but it was about three times less sensitive to purine nucleotide inhibition. Strikingly, only ?15% of epididymal beige adipocytes had IH, while in the rest UCP1-dependent IH was undetectable. Despite the absence of UCP1 in the majority of epididymal beige adipocytes, these cells employ prominent creatine cycling as a UCP1-independent thermogenic mechanism.

| S-EPMC5448977 | biostudies-literature

Localized products of futile cycle/lrmp promote centrosome-nucleus attachment in the zebrafish zygote.

Project description:BackgroundThe centrosome has a well-established role as a microtubule organizer during mitosis and cytokinesis. In addition, it facilitates the union of parental haploid genomes following fertilization by nucleating a microtubule aster along which the female pronucleus migrates toward the male pronucleus. Stable associations between the sperm aster and the pronuclei are essential during this directed movement.ResultsOur studies reveal that the zebrafish gene futile cycle (fue) is required in the zygote for male pronucleus-centrosome attachment and female pronuclear migration. We show that fue encodes a novel, maternally-provided long form of lymphoid-restricted membrane protein (lrmp), a vertebrate-specific gene of unknown function. Both maternal lrmp messenger RNA (mRNA) and protein are highly localized in the zygote, in a largely overlapping pattern at nuclear membranes, centrosomes, and spindles. Truncated Lrmp-EGFP fusion proteins identified subcellular targeting signals in the C terminus of Lrmp; however, endogenous mRNA localization is likely important to ensure strict spatial expression of the protein. Localization of both Lrmp protein and lrmp RNA is defective in fue mutant embryos, indicating that correct targeting of lrmp gene products is dependent on Lrmp function.ConclusionsLrmp is a conserved vertebrate gene whose maternally inherited products are essential for nucleus-centrosome attachment and pronuclear congression during fertilization. Precise subcellular localization of lrmp products also suggests a requirement for strict spatiotemporal regulation of their function in the early embryo.

| S-EPMC3360835 | biostudies-literature

Single nucleus transcriptomics of ventral midbrain identifies glial activation associated with chronic opioid use disorder.

Project description:Dynamic interactions of neurons and glia in the ventral midbrain mediate reward and addiction behavior. We studied gene expression in 212,713 ventral midbrain single nuclei from 95 individuals with history of opioid misuse, and individuals without drug exposure. Chronic exposure to opioids was not associated with change in proportions of glial and neuronal subtypes, however glial transcriptomes were broadly altered, involving 9.5 - 6.2% of expressed genes within microglia, oligodendrocytes, and astrocytes. Genes associated with activation of the immune response including interferon, NFkB signaling, and cell motility pathways were upregulated, contrasting with down-regulated expression of synaptic signaling and plasticity genes in ventral midbrain non-dopaminergic neurons. Ventral midbrain transcriptomic reprogramming in the context of chronic opioid exposure included 325 genes that previous genome-wide studies had linked to risk of substance use traits in the broader population, thereby pointing to heritable risk architectures in the genomic organization of the brain's reward circuitry.

| S-EPMC10497570 | biostudies-literature

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