Abstract：
:We previously demonstrated that low biosynthesis of ω-3 fatty acid-derived proresolution mediators, termed protectins, is associated with an impaired global resolution capacity, inflammation and insulin resistance in obese high-fat diet-fed mice. These findings prompted a more direct study of the therapeutic potential of protectins for the treatment of metabolic disorders. Herein we show that protectin DX (PDX) exerts an unanticipated glucoregulatory activity that is distinct from its anti-inflammatory actions. We found that PDX selectively stimulated the release of the prototypic myokine interleukin-6 (IL-6) from skeletal muscle and thereby initiated a myokine-liver signaling axis, which blunted hepatic glucose production via signal transducer and activator of transcription 3 (STAT3)-mediated transcriptional suppression of the gluconeogenic program. These effects of PDX were abrogated in Il6-null mice. PDX also activated AMP-activated protein kinase (AMPK); however, it did so in an IL-6-independent manner. Notably, we demonstrated that administration of PDX to obese diabetic db/db mice raises skeletal muscle IL-6 levels and substantially improves their insulin sensitivity without any impact on adipose tissue inflammation. Our findings thus support the development of PDX-based selective muscle IL-6 secretagogues as a new class of therapy for the treatment of insulin resistance and type 2 diabetes.
journal_name
Nat Medjournal_title
Nature medicineauthors
White PJ,St-Pierre P,Charbonneau A,Mitchell PL,St-Amand E,Marcotte B,Marette Adoi
10.1038/nm.3549subject
Has Abstractpub_date
2014-06-01 00:00:00pages
664-9issue
6eissn
1078-8956issn
1546-170Xpii
nm.3549journal_volume
20pub_type
杂志文章相关文献
NATURE MEDICINE文献大全abstract：:One function of the glucocorticoid receptor (GR) in corticotroph cells is to suppress the transcription of the gene encoding proopiomelanocortin (POMC), the precursor of the stress hormone adrenocorticotropin (ACTH). Cushing disease is a neuroendocrine condition caused by partially glucocorticoid-resistant corticotrop...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm.3776
更新日期：2015-03-01 00:00:00
abstract：:Mice carrying mutations in both the dystrophin and utrophin genes die prematurely as a consequence of severe muscular dystrophy. Here, we show that intravascular administration of recombinant adeno-associated viral (rAAV) vectors carrying a microdystrophin gene restores expression of dystrophin in the respiratory, car...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm1439
更新日期：2006-07-01 00:00:00
abstract：: ...
journal_title：Nature medicine
pub_type： 评论,杂志文章
doi：10.1038/s41591-018-0332-z
更新日期：2019-01-01 00:00:00
abstract：:Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that exhibits specific tumoricidal activity against a variety of tumors. It is expressed on different cells of the immune system and plays a role in natural killer cell-mediated tumor surveillance. In allogeneic he...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm1202-797
更新日期：2002-12-01 00:00:00
abstract：:Temperatures that deviate from the long-term local norm affect human health, and are projected to become more frequent as the global climate changes1. There are limited data on how such anomalies affect deaths from injuries. In the present study, we used data on mortality and temperature over 38 years (1980-2017) in t...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/s41591-019-0721-y
更新日期：2020-01-01 00:00:00
abstract：:Alzheimer's disease (AD) is a neurodegenerative disorder involving the florid deposition of vascular and cerebral plaques composed chiefly of amyloid beta-peptide (A beta) derived from cleavage of the amyloid precursor protein (APP). Varying in length from 39 to 43 amino acids, A beta, particularly the longer A beta(4...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm0997-1021
更新日期：1997-09-01 00:00:00
abstract：:Telomerase is a ribonucleoprotein enzyme that maintains the protective structures at the ends of eukaryotic chromosomes, called telomeres. In most human somatic cells, telomerase expression is repressed, and telomeres shorten progressively with each cell division. In contrast, most human tumors express telomerase, res...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/13495
更新日期：1999-10-01 00:00:00
abstract：:Natalizumab (NZM), a humanized monoclonal IgG4 antibody to α4 integrins, is used to treat patients with relapsing-remitting multiple sclerosis (MS)1,2, but in about 6% of the cases persistent neutralizing anti-drug antibodies (ADAs) are induced leading to therapy discontinuation3,4. To understand the basis of the ADA ...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/s41591-019-0568-2
更新日期：2019-09-01 00:00:00
abstract：:Cystinuria is an incompletely dominant disorder characterized by defective urinary cystine reabsorption that results in the formation of cystine-based urinary stones. Current treatment options are limited in their effectiveness at preventing stone recurrence and are often poorly tolerated. We report that the nutrition...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm.4280
更新日期：2017-03-01 00:00:00
abstract：:Internalization of targeted therapeutics is often needed for efficacy, but also alters drug penetration of a tissue. A new model explores the trade-offs of intracellular drug trafficking. ...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm1195-1135
更新日期：1995-11-01 00:00:00
abstract：:The adoptive transfer of T cells engineered with a chimeric antigen receptor (CAR) (hereafter referred to as CAR-T cells) specific for the B lymphocyte antigen CD19 has shown impressive clinical responses in patients with refractory B cell malignancies. However, the therapeutic effects of CAR-T cells that target other...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm.4478
更新日期：2018-03-01 00:00:00
abstract：:Targeted gene transduction to specific tissues and organs through intravenous injection would be the ultimate preferred method of gene delivery. Here, we report successful targeting in a living animal through intravenous injection of a lentiviral vector pseudotyped with a modified chimeric Sindbis virus envelope (term...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm1192
更新日期：2005-03-01 00:00:00
abstract：:White fat stores excess energy, whereas brown and beige fat are thermogenic and dissipate energy as heat. Thermogenic adipose tissues markedly improve glucose and lipid homeostasis in mouse models, although the extent to which brown adipose tissue (BAT) influences metabolic and cardiovascular disease in humans is uncl...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/s41591-020-1126-7
更新日期：2021-01-01 00:00:00
abstract：:De novo mutations arising on the paternal chromosome make the largest known contribution to autism risk, and correlate with paternal age at the time of conception. The recurrence risk for autism spectrum disorders is substantial, leading many families to decline future pregnancies, but the potential impact of assessin...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/s41591-019-0711-0
更新日期：2020-01-01 00:00:00
abstract：:Direct evidence in humans for the impact of the microbiome on nutrient absorption is lacking. We conducted an extended inpatient study using two interventions that we hypothesized would alter the gut microbiome and nutrient absorption. In each, stool calorie loss, a direct proxy of nutrient absorption, was measured. T...
journal_title：Nature medicine
pub_type： 杂志文章,随机对照试验
doi：10.1038/s41591-020-0801-z
更新日期：2020-04-01 00:00:00
abstract：:Focal segmental glomerulosclerosis (FSGS) is a frequent and severe glomerular disease characterized by destabilization of podocyte foot processes. We report that transgenic expression of the microRNA miR-193a in mice rapidly induces FSGS with extensive podocyte foot process effacement. Mechanistically, miR-193a inhibi...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm.3142
更新日期：2013-04-01 00:00:00
abstract：:Although the treatment of acute myeloid leukemia (AML) has improved substantially in the past three decades, more than half of all patients develop disease that is refractory to intensive chemotherapy. Functional genomics approaches offer a means to discover specific molecules mediating the aberrant growth and surviva...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm.2819
更新日期：2012-07-01 00:00:00
abstract：:Retinoic acid and arsenic trioxide target the protein stability and transcriptional repression activity of the fusion oncoprotein PML-RARA, resulting in regression of acute promyelocytic leukemia (APL). Phenotypically, retinoic acid induces differentiation of APL cells. Here we show that retinoic acid also triggers gr...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm.1891
更新日期：2008-12-01 00:00:00
abstract：: ...
journal_title：Nature medicine
pub_type： 评论,杂志文章
doi：10.1038/s41591-019-0397-3
更新日期：2019-03-01 00:00:00
abstract：:HIV-specific mucosal and cellular immunity was analyzed in heterosexual couples discordant for HIV status in serum and in HIV-unexposed controls. HIV-specific IgA but not IgG was present in urine and vaginal wash samples from HIV-exposed seronegative individuals (ESN), whereas both IgA and IgG were observed in their H...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm1197-1250
更新日期：1997-11-01 00:00:00
abstract：:Chlamydia trachomatis is the leading cause worldwide of preventable infectious blindness (trachoma) and sexually transmitted disease, including nongonoccocal urethritis and pelvic inflammatory disease. To date, no effective vaccine against C. trachomatis infection has been identified. A monoclonal anti-idiotypic antib...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm1096-1116
更新日期：1996-10-01 00:00:00
abstract：:How should clinical trials be improved? Ken Getz, a senior fellow at the Tufts Center for the Study of Drug Development, has been thinking up answers to this question for two decades. In 2003, Getz took on a new challenge when he launched the Center for Information & Study on Clinical Research, a nonprofit focused on ...
journal_title：Nature medicine
pub_type： 面试
doi：10.1038/nm0210-154
更新日期：2010-02-01 00:00:00
abstract：:It begins as a slowly expanding spot of light or similar visual disturbance, often accompanied by phantom noises and other sensory distortions. People who experience such 'auras' know all too well that these early warning signs will culminate in a head-splitting migraine, yet scientists have little idea what causes th...
journal_title：Nature medicine
pub_type： 新闻
doi：10.1038/nm0913-1083
更新日期：2013-09-01 00:00:00
abstract：:Owing to recent medical and technological advances in neonatal care, infants born extremely premature have increased survival rates1,2. After birth, these infants are at high risk of hypoxic episodes because of lung immaturity, hypotension and lack of cerebral-flow regulation, and can develop a severe condition called...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/s41591-019-0436-0
更新日期：2019-05-01 00:00:00
abstract：:Cells from the telomerase knockout mouse immortalize with an approximately ten million-fold greater frequency than human cells. In this commentary, Wright and Shay discuss the implications of this difference between mice and men and its relationship to cancer. ...
journal_title：Nature medicine
pub_type： 杂志文章,评审
doi：10.1038/78592
更新日期：2000-08-01 00:00:00
abstract：:Overexpression of the B7-H1 (PD-L1) molecule in the tumor microenvironment (TME) is a major immune evasion mechanism in some patients with cancer, and antibody blockade of the B7-H1/PD-1 interaction can normalize compromised immunity without excessive side-effects. Using a genome-scale T cell activity array, we identi...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/s41591-019-0374-x
更新日期：2019-04-01 00:00:00
abstract：:The molecular alterations that occur in cells before cancer is manifest are largely uncharted. Lung carcinoma in situ (CIS) lesions are the pre-invasive precursor to squamous cell carcinoma. Although microscopically identical, their future is in equipoise, with half progressing to invasive cancer and half regressing o...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/s41591-018-0323-0
更新日期：2019-03-01 00:00:00
abstract：:Targeting the mammalian target of rapamycin (mTOR) protein is a promising strategy for cancer therapy. The mTOR kinase functions in two complexes, TORC1 (target of rapamycin complex-1) and TORC2 (target of rapamycin complex-2); however, neither of these complexes is fully inhibited by the allosteric inhibitor rapamyci...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm.2091
更新日期：2010-02-01 00:00:00
abstract：:In the version of this article originally published, there was an error in the legend for Extended Data Fig. 7. The legend for panel f was originally: "f, FACS analysis of IL7R-, CD62L- and CD45RA- expression on TRAC-1928ζ and TRAC-1XX CAR T cells at day 63 post CAR infusion (representative for at least n = 3 mice per...
journal_title：Nature medicine
pub_type： 已发布勘误
doi：10.1038/s41591-019-0360-3
更新日期：2019-03-01 00:00:00
abstract：:In the nervous system, NMDA receptors (NMDARs) participate in neurotransmission and modulate the viability of neurons. In contrast, little is known about the role of NMDARs in pancreatic islets and the insulin-secreting beta cells whose functional impairment contributes to diabetes mellitus. Here we found that inhibit...
journal_title：Nature medicine
pub_type： 杂志文章
doi：10.1038/nm.3822
更新日期：2015-04-01 00:00:00
