Abstract:
:Leptin has beneficial effects on glucose metabolism via actions in the hypothalamus, but the roles of specific subgroups of neurons responsible for these antidiabetic effects remain unresolved. We generated diabetic Lep(ob/ob) or Lepr(db/db) mice lacking or re-expressing leptin receptors (LepRb) in subgroups of neurons to explore their contributions to leptin's glucose-lowering actions. We show that agouti-related peptide (AgRP)-expressing neurons are both required and sufficient to correct hyperglycemia by leptin. LepRb in pro-opiomelanocortin (POMC) neurons or steroidogenic factor-1 (SF1) neurons are not required. Furthermore, normalization of blood glucose by leptin is blunted in Lep(ob/ob)/MC4R-null mice, but not in Lep(ob/ob) mice lacking neuropeptide Y (NPY) or gamma-aminobutyric acid (GABA) in AgRP neurons. Leptin's ability to improve glucose balance is accompanied by a reduction in circulating glucagon. We conclude that AgRP neurons play a crucial role in glucose-lowering actions by leptin and that this requires the melanocortin system, but not NPY and GABA.
journal_name
Cell Repjournal_title
Cell reportsauthors
Gonçalves GH,Li W,Garcia AV,Figueiredo MS,Bjørbæk Cdoi
10.1016/j.celrep.2014.04.010subject
Has Abstractpub_date
2014-05-22 00:00:00pages
1093-103issue
4issn
2211-1247pii
S2211-1247(14)00297-6journal_volume
7pub_type
杂志文章相关文献
Cell Reports文献大全abstract::Genetically encoded effectors are important tools for probing cellular function in living animals, but improved methods for directing their expression to specific cell types are required. Here, we introduce a simple, versatile method for achieving cell-type-specific expression of transgenes that leverages the untapped...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.01.059
更新日期:2015-03-03 00:00:00
abstract::Brain networks contain a large diversity of functionally distinct neuronal elements, each with unique properties, enabling computational capacities and supporting brain functions. Understanding their functional implications for behavior requires the precise identification of the cell types of a network and in vivo mon...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.11.042
更新日期:2014-12-24 00:00:00
abstract::In neurons, transmembrane proteins are targeted to dendrites in vesicles that traffic solely within the somatodendritic compartment. How these vesicles are retained within the somatodendritic domain is unknown. Here, we use a novel pulse-chase system, which allows synchronous release of exogenous transmembrane protein...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2012.05.018
更新日期:2012-07-26 00:00:00
abstract::Inhibition of RNA polymerase I (Pol I) is a promising strategy for modern cancer therapy. BMH-21 is a first-in-class small molecule that inhibits Pol I transcription and induces degradation of the enzyme, but how this exceptional response is enforced is not known. Here, we define key elements requisite for the respons...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.03.066
更新日期:2018-04-10 00:00:00
abstract::Bromodomain and extra-terminal domain (BET) family inhibitors offer an approach to treating hematological malignancies. We used precision nuclear run-on transcription sequencing (PRO-seq) to create high-resolution maps of active RNA polymerases across the genome in t(8;21) acute myeloid leukemia (AML), as these polyme...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.07.032
更新日期:2016-08-16 00:00:00
abstract::Organismal death is a process of systemic collapse whose mechanisms are less well understood than those of cell death. We previously reported that death in C. elegans is accompanied by a calcium-propagated wave of intestinal necrosis, marked by a wave of blue autofluorescence (death fluorescence). Here, we describe an...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.02.050
更新日期:2018-03-06 00:00:00
abstract::MyoD and NeuroD2, master regulators of myogenesis and neurogenesis, bind to a "shared" E-box sequence (CAGCTG) and a "private" sequence (CAGGTG or CAGATG, respectively). To determine whether private-site recognition is sufficient to confer lineage specification, we generated a MyoD mutant with the DNA-binding specific...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.02.055
更新日期:2015-03-31 00:00:00
abstract::At presynaptic active zones, exocytosis of neurotransmitter vesicles (SVs) is driven by SNARE complexes that recruit Syb2 and SNAP25. However, it remains unknown which SNAREs promote the secretion of neuronal proteins, including those essential for circuit development and experience-dependent plasticity. Here we demon...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.04.032
更新日期:2015-05-19 00:00:00
abstract::AMPK exerts prolongevity effects in diverse species; however, the tissue-specific mechanisms involved are poorly understood. Here, we show that upregulation of AMPK in the adult Drosophila nervous system induces autophagy both in the brain and also in the intestinal epithelium. Induction of autophagy is linked to impr...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.08.006
更新日期:2014-09-25 00:00:00
abstract::Oct4 is an essential regulator of pluripotency in vivo and in vitro in embryonic stem cells, as well as a key mediator of the reprogramming of somatic cells into induced pluripotent stem cells. It is not known whether activation and/or repression of specific genes by Oct4 is relevant to these functions. Here, we show ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2011.12.002
更新日期:2012-02-23 00:00:00
abstract::Mucus separates gut-luminal microbes from the tissue. It is unclear how pathogens like Salmonella Typhimurium (S.Tm) can overcome this obstacle. Using live microscopy, we monitored S.Tm interactions with native murine gut explants and studied how mucus affects the infection. A dense inner mucus layer covers the distal...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.04.106
更新日期:2019-05-28 00:00:00
abstract::High-throughput imaging has led to an explosion of observations about cell-size homeostasis across the kingdoms of life. Among bacteria, "adder" behavior-in which a constant size increment appears to be added during each cell cycle-is ubiquitous, while various eukaryotes show other size-homeostasis behaviors. Since in...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2020.107992
更新日期:2020-08-11 00:00:00
abstract::In the eukaryotic cell, spliceosomes assemble onto pre-mRNA cotranscriptionally. Spliceosome assembly takes place in the context of the chromatin environment, suggesting that the state of the chromatin may affect splicing. The molecular details and mechanisms through which chromatin affects splicing, however, are stil...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.05.100
更新日期:2019-06-25 00:00:00
abstract::Effective approaches to neuropsychiatric disorders require detailed understanding of the cellular composition and circuitry of the complex mammalian brain. Here, we present a paradigm for deconstructing the diversity of neurons defined by a specific neurotransmitter using a microfluidic dynamic array to simultaneously...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.10.008
更新日期:2014-11-06 00:00:00
abstract::During development, two cell types born from closely related progenitor pools often express identical transcriptional regulators despite their completely distinct characteristics. This phenomenon implies the need for a mechanism that operates to segregate the identities of the two cell types throughout differentiation...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.06.100
更新日期:2016-08-09 00:00:00
abstract::Endosomal sorting complexes required for transport (ESCRT) drive cell surface receptor degradation resulting in attenuation of oncogenic signaling and pointing to a tumor suppressor function. Here, we show that loss of function of an ESCRT protein (HD-PTP encoded by the PTPN23 gene, located on the tumor suppressor gen...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.04.076
更新日期:2016-05-31 00:00:00
abstract::Reactive astrogliosis is an essential and ubiquitous response to CNS injury, but in some cases, aberrant activation of astrocytes and their release of inhibitory signaling molecules can impair endogenous neural repair processes. Our lab previously identified a secreted intercellular signaling molecule, called endothel...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.11.002
更新日期:2015-12-15 00:00:00
abstract::Accumulation of toxic amyloid oligomers is a key feature in the pathogenesis of amyloid-related diseases. Formation of mature amyloid fibrils is one defense mechanism to neutralize toxic prefibrillar oligomers. This mechanism is notably influenced by apolipoprotein E variants. Cells that produce mature amyloid fibrils...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2015.08.057
更新日期:2015-10-06 00:00:00
abstract::Most tumor cells exhibit obligatory demands for essential amino acids (EAAs), but the regulatory mechanisms whereby tumor cells take up EAAs and EAAs promote malignant transformation remain to be determined. Here, we show that oncogenic MYC, solute carrier family (SLC) 7 member 5 (SLC7A5), and SLC43A1 constitute a fee...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.12.002
更新日期:2017-12-26 00:00:00
abstract::Katanin was the first microtubule (MT)-severing enzyme discovered, but how katanin executes MT severing remains poorly understood. Here, we report X-ray crystal structures of the apo and ATPγS-bound states of the catalytic AAA domain of human katanin p60 at 3.0 and 2.9 Å resolution, respectively. Comparison of the two...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.01.020
更新日期:2019-01-29 00:00:00
abstract::Obesity modifies T cell populations in adipose tissue, thereby contributing to adipose tissue inflammation and insulin resistance. Here, we show that Rab4b, a small GTPase governing endocytic trafficking, is pivotal in T cells for the development of these pathological events. Rab4b expression is decreased in adipose T...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.11.083
更新日期:2018-12-18 00:00:00
abstract::The transcription factors (TFs) Nanog and Esrrb play important roles in embryonic stem cells (ESCs) and during primordial germ-cell (PGC) development. Esrrb is a positively regulated direct target of NANOG in ESCs that can substitute qualitatively for Nanog function in ESCs. Whether this functional substitution extend...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.12.060
更新日期:2018-01-09 00:00:00
abstract::The cellular responses induced by mitochondrial dysfunction remain elusive. Intrigued by the lack of almost any glomerular phenotype in patients with profound renal ischemia, we comprehensively investigated the primary sources of energy of glomerular podocytes. Combining functional measurements of oxygen consumption r...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.04.012
更新日期:2019-04-30 00:00:00
abstract::Huntington's disease (HD) is a monogenic neurodegenerative disorder representing an ideal candidate for gene silencing with oligonucleotide therapeutics (i.e., antisense oligonucleotides [ASOs] and small interfering RNAs [siRNAs]). Using an ultra-sensitive branched fluorescence in situ hybridization (FISH) method, we ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2018.07.106
更新日期:2018-09-04 00:00:00
abstract::Even though hyperthermia is a promising treatment for cancer, the relationship between specific temperatures and clinical benefits and predictors of sensitivity of cancer to hyperthermia is poorly understood. Ovarian and uterine tumors have diverse hyperthermia sensitivities. Integrative analyses of the specific gene ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.10.020
更新日期:2016-11-01 00:00:00
abstract::MicroRNA (miRNA) transfer via exosomes may mediate cell-to-cell communication. Interestingly, specific miRNAs are enriched in exosomes in a cell-type-dependent fashion. However, the mechanisms whereby miRNAs are sorted to exosomes and the significance of miRNA transfer to acceptor cells are unclear. We used macrophage...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2014.07.035
更新日期:2014-09-11 00:00:00
abstract::The notion that decapping leads irreversibly to messenger RNA (mRNA) decay was contradicted by the identification of capped transcripts missing portions of their 5' ends and a cytoplasmic complex that can restore the cap on uncapped mRNAs. In this study, we used accumulation of uncapped transcripts in cells inhibited ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2012.07.011
更新日期:2012-09-27 00:00:00
abstract::Microglia have important remodeling functions in neurodevelopment, aging, and disease, with evidence for molecular diversity. However, the signaling pathways and environmental cues that drive diverse states of microglia are incompletely understood. We profiled microglia of a discrete developing CNS region, the murine ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2019.04.062
更新日期:2019-05-14 00:00:00
abstract::Recent studies have elucidated the molecular mechanism of RORγT transcriptional regulation of Th17 differentiation and function. RORγT was initially identified as a transcription factor required for thymopoiesis by maintaining survival of CD4+CD8+ (DP) thymocytes. While RORγ antagonists are currently being developed t...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2016.11.073
更新日期:2016-12-20 00:00:00
abstract::The circadian clock generates biological rhythms of metabolic and physiological processes, including the sleep-wake cycle. We previously identified a missense mutation in the flavin adenine dinucleotide (FAD) binding pocket of CRYPTOCHROME2 (CRY2), a clock protein that causes human advanced sleep phase. This prompted ...
journal_title:Cell reports
pub_type: 杂志文章
doi:10.1016/j.celrep.2017.03.041
更新日期:2017-04-11 00:00:00