Abstract:
:The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) was targeted in mice. PGC-1alpha null (PGC-1alpha(-/-)) mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha(-/-) mice. With age, the PGC-1alpha(-/-) mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha(-/-) mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha(-/-) mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha(-/-) mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha(-/-) mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha(-/-) mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha(-/-) mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.
journal_name
PLoS Bioljournal_title
PLoS biologyauthors
Leone TC,Lehman JJ,Finck BN,Schaeffer PJ,Wende AR,Boudina S,Courtois M,Wozniak DF,Sambandam N,Bernal-Mizrachi C,Chen Z,Holloszy JO,Medeiros DM,Schmidt RE,Saffitz JE,Abel ED,Semenkovich CF,Kelly DPdoi
10.1371/journal.pbio.0030101keywords:
subject
Has Abstractpub_date
2005-04-01 00:00:00pages
e101issue
4eissn
1544-9173issn
1545-7885pii
04-PLBI-RA-0782R2journal_volume
3pub_type
杂志文章相关文献
PLOS BIOLOGY文献大全abstract::Certain bacterial adhesins appear to promote a pathogen's extracellular lifestyle rather than its entry into host cells. However, little is known about the stimuli elicited upon such pathogen host-cell interactions. Here, we report that type IV pili (Tfp)-producing Neisseria gonorrhoeae (P(+)GC) induces an immediate r...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1000457
更新日期:2010-08-24 00:00:00
abstract::The most consistent result in more than two decades of experimental evolution is that the fitness of populations adapting to a constant environment does not increase indefinitely, but reaches a plateau. Using experimental evolution with bacteriophage, we show here that the converse is also true. In populations small e...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0050094
更新日期:2007-04-01 00:00:00
abstract::Blood-brain barrier (BBB) defects and cerebrovascular dysfunction contribute to amyloid-β (Aβ) brain accumulation and drive Alzheimer disease (AD) pathology. By regulating vascular functions and inflammation in the microvasculature, a disintegrin and metalloprotease with thrombospondin type I motif, member 13 (ADAMTS1...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.3000313
更新日期:2019-06-11 00:00:00
abstract::Single-cell imaging, combined with recent advances in image analysis and microfluidic technologies, have enabled fundamental discoveries of cellular responses to chemical perturbations that are often obscured by traditional liquid-culture experiments. Temperature is an environmental variable well known to impact growt...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.3000786
更新日期:2020-11-06 00:00:00
abstract::Long distance migration of differentiating granule cells from the cerebellar upper rhombic lip has been reported in many vertebrates. However, the knowledge about the subcellular dynamics and molecular mechanisms regulating directional neuronal migration in vivo is just beginning to emerge. Here we show by time-lapse ...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1000240
更新日期:2009-11-01 00:00:00
abstract::The causes and mechanisms of evolutionary diversification are central issues in biology. Geographic isolation is the traditional explanation for diversification, but recent theoretical and empirical studies have shown that frequency-dependent selection can drive diversification without isolation and that adaptive dive...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1001490
更新日期:2013-01-01 00:00:00
abstract::Within the human host, the malaria parasite Plasmodium falciparum is exposed to multiple selection pressures. The host environment changes dramatically in severe malaria, but the extent to which the parasite responds to-or is selected by-this environment remains unclear. From previous studies, the parasites that cause...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.2004328
更新日期:2018-03-12 00:00:00
abstract::Patterned spontaneous activity in the developing retina is necessary to drive synaptic refinement in the lateral geniculate nucleus (LGN). Using perforated patch recordings from neurons in LGN slices during the period of eye segregation, we examine how such burst-based activity can instruct this refinement. Retinogeni...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0050061
更新日期:2007-03-01 00:00:00
abstract::Individual synapses vary significantly in their neurotransmitter release properties, which underlie complex information processing in neural circuits. Presynaptic Ca2+ homeostasis plays a critical role in specifying neurotransmitter release properties, but the mechanisms regulating synapse-specific Ca2+ homeostasis in...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1002516
更新日期:2016-07-18 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pbio.1002125.]. ...
journal_title:PLoS biology
pub_type: 已发布勘误
doi:10.1371/journal.pbio.1002163
更新日期:2015-05-14 00:00:00
abstract::Citizen science is mainstream: millions of people contribute data to a growing array of citizen science projects annually, forming massive datasets that will drive research for years to come. Many citizen science projects implement a "leaderboard" framework, ranking the contributions based on number of records or spec...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.3000357
更新日期:2019-06-27 00:00:00
abstract::Courtship is a widespread behavior in which one gender conveys to the other a series of cues about their species identity, gender, and suitability as mates. In many species, females decode these male displays and either accept or reject them. Despite the fact that courtship has been investigated for a long time, the g...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1001964
更新日期:2014-10-07 00:00:00
abstract::Morphogen gradients are established by the localized production and subsequent diffusion of signaling molecules. It is generally assumed that cell fates are induced only after morphogen profiles have reached their steady state. Yet, patterning processes during early development occur rapidly, and tissue patterning may...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0050046
更新日期:2007-02-01 00:00:00
abstract::Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framewo...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1002394
更新日期:2016-03-02 00:00:00
abstract::Dopamine guides behavior and learning through pleasure, according to classic understanding. Dopaminergic neurons are traditionally thought to signal positive or negative prediction errors (PEs) when reward expectations are, respectively, exceeded or not matched. These signed PEs are quite different from the unsigned P...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.3000744
更新日期:2020-06-19 00:00:00
abstract::All organisms live in temporally fluctuating environments. Theory predicts that the evolution of deterministic maternal effects (i.e., anticipatory maternal effects or transgenerational phenotypic plasticity) underlies adaptation to environments that fluctuate in a predictably alternating fashion over maternal-offspri...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1002388
更新日期:2016-02-24 00:00:00
abstract::PolD is an archaeal replicative DNA polymerase (DNAP) made of a proofreading exonuclease subunit (DP1) and a larger polymerase catalytic subunit (DP2). Recently, we reported the individual crystal structures of the DP1 and DP2 catalytic cores, thereby revealing that PolD is an atypical DNAP that has all functional pro...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.3000122
更新日期:2019-01-18 00:00:00
abstract::After mitosis, mammalian chromosomes partially decondense to occupy distinct territories in the cell nucleus. Current models propose that territories are separated by an interchromatin domain, rich in soluble nuclear machinery, where only rare interchromosomal interactions can occur via extended chromatin loops. In co...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0040138
更新日期:2006-05-01 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pbio.2001951.]. ...
journal_title:PLoS biology
pub_type: 已发布勘误
doi:10.1371/journal.pbio.1002603
更新日期:2017-05-01 00:00:00
abstract::Bax/Bak-mediated mitochondrial outer membrane permeabilization (MOMP) is essential for "intrinsic" apoptotic cell death. Published studies used synthetic liposomes to reveal an intrinsic pore-forming activity of Bax, but it is unclear how other mitochondrial outer membrane (MOM) proteins might facilitate this function...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1001394
更新日期:2012-01-01 00:00:00
abstract::One of the major challenges of functional genomics is to unravel the connection between genotype and phenotype. So far no global analysis has attempted to explore those connections in the light of the large phenotypic variability seen in nature. Here, we use an unsupervised, systematic approach for associating genes a...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0030134
更新日期:2005-05-01 00:00:00
abstract::Neuronal migration during embryonic development contributes to functional brain circuitry. Many neurons migrate in morphologically distinct stages that coincide with differentiation, requiring tight spatial regulation. It had been proposed that neurotransmitter-mediated activity could exert this control. Here, we demo...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.2002226
更新日期:2018-01-04 00:00:00
abstract::It has been reported that feeding mice resveratrol activates AMPK and SIRT1 in skeletal muscle leading to deacetylation and activation of PGC-1α, increased mitochondrial biogenesis, and improved running endurance. This study was done to further evaluate the effects of resveratrol, SIRT1, and PGC-1α deacetylation on mi...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1001603
更新日期:2013-07-01 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pbio.1002436.]. ...
journal_title:PLoS biology
pub_type: 已发布勘误
doi:10.1371/journal.pbio.1002494
更新日期:2016-06-08 00:00:00
abstract::Developmental biology (including embryology) is proposed as "the stem cell of biological disciplines." Genetics, cell biology, oncology, immunology, evolutionary mechanisms, neurobiology, and systems biology each has its ancestry in developmental biology. Moreover, developmental biology continues to roll on, budding o...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.2003691
更新日期:2017-12-28 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pbio.2004814.]. ...
journal_title:PLoS biology
pub_type: 杂志文章,已发布勘误
doi:10.1371/journal.pbio.1002619
更新日期:2018-01-25 00:00:00
abstract::To elucidate the history of living and extinct elephantids, we generated 39,763 bp of aligned nuclear DNA sequence across 375 loci for African savanna elephant, African forest elephant, Asian elephant, the extinct American mastodon, and the woolly mammoth. Our data establish that the Asian elephant is the closest livi...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1000564
更新日期:2010-12-21 00:00:00
abstract::The signals that initiate cell invasion are not well understood, but there is increasing evidence that extracellular physical signals play an important role. Here we show that epithelial cell invasion in the intestine of zebrafish meltdown (mlt) mutants arises in response to unregulated contractile tone in the surroun...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.1001386
更新日期:2012-01-01 00:00:00
abstract::There is a widespread concern about the direct and indirect effects of industrial fisheries; this concern is particularly pertinent for so-called "marine protected areas" (MPAs), which should be safeguarded by national and international law. The intertidal flats of the Dutch Wadden Sea are a State Nature Monument and ...
journal_title:PLoS biology
pub_type: 杂志文章
doi:10.1371/journal.pbio.0040376
更新日期:2006-11-01 00:00:00
abstract::[This corrects the article DOI: 10.1371/journal.pbio.3000193.]. ...
journal_title:PLoS biology
pub_type: 杂志文章,已发布勘误
doi:10.1371/journal.pbio.3000752
更新日期:2020-05-18 00:00:00