Abstract:
OBJECTIVE:Estrogen receptor-α (ERα) is a nuclear receptor family member thought to substantially contribute to the metabolic regulation of skeletal muscle. However, previous mouse models utilized to assess the necessity of ERα signaling in skeletal muscle were confounded by altered developmental programming and/or influenced by secondary effects, making it difficult to assign a causal role for ERα. The objective of this study was to determine the role of skeletal muscle ERα in regulating metabolism in the absence of confounding factors of development. METHODS:A novel mouse model was developed allowing for induced deletion of ERα in adult female skeletal muscle (ERαKOism). ERαshRNA was also used to knockdown ERα (ERαKD) in human myotubes cultured from primary human skeletal muscle cells isolated from muscle biopsies from healthy and obese insulin-resistant women. RESULTS:Twelve weeks of HFD exposure had no differential effects on body composition, VO2, VCO2, RER, energy expenditure, and activity counts across genotypes. Although ERαKOism mice exhibited greater glucose intolerance than wild-type (WT) mice after chronic HFD, ex vivo skeletal muscle glucose uptake was not impaired in the ERαKOism mice. Expression of pro-inflammatory genes was altered in the skeletal muscle of the ERαKOism, but the concentrations of these inflammatory markers in the systemic circulation were either lower or remained similar to the WT mice. Finally, skeletal muscle mitochondrial respiratory capacity, oxidative phosphorylation efficiency, and H2O2 emission potential was not affected in the ERαKOism mice. ERαKD in human skeletal muscle cells neither altered differentiation capacity nor caused severe deficits in mitochondrial respiratory capacity. CONCLUSIONS:Collectively, these results suggest that ERα function is superfluous in protecting against HFD-induced skeletal muscle metabolic derangements after postnatal development is complete.
journal_name
Mol Metabjournal_title
Molecular metabolismauthors
Iñigo MR,Amorese AJ,Tarpey MD,Balestrieri NP,Jones KG,Patteson DJ,Jackson KC,Torres MJ,Lin CT,Smith CD,Heden TD,McMillin SL,Weyrauch LA,Stanley EC,Schmidt CA,Kilburg-Basnyat BB,Reece SW,Psaltis CE,Leinwand LA,Funaidoi
10.1016/j.molmet.2019.12.010subject
Has Abstractpub_date
2020-04-01 00:00:00pages
1-15issn
2212-8778pii
S2212-8778(19)30961-5journal_volume
34pub_type
杂志文章abstract::Brain mitochondrial activity is centrally involved in the central control of energy balance. When studying mitochondrial functions in the brain, however, discrepant results might be obtained, depending on the experimental approaches. For instance, immunostaining experiments and biochemical isolation of organelles expo...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2014.03.007
更新日期:2014-04-02 00:00:00
abstract:OBJECTIVE:In the adult brain, neural stem cells (NSCs) located in the subventricular zone (SVZ) produce both neuronal and glial cells. Thyroid hormones (THs) regulate adult NSC differentiation towards a neuronal phenotype, but also have major roles in mitochondrial metabolism. As NSC metabolism relies mainly on glycoly...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.08.003
更新日期:2017-11-01 00:00:00
abstract:OBJECTIVE:A major challenge for obesity treatment is the maintenance of reduced body weight. Diet-induced obese mice are resistant to achieving normoweight once the obesogenic conditions are reversed, in part because lowered circulating leptin leads to a reduction in metabolic rate and a rebound of hyperphagia that def...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.07.012
更新日期:2016-08-05 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.03.003
更新日期:2017-03-18 00:00:00
abstract:OBJECTIVES:Hepatic insulin resistance is a hallmark of type 2 diabetes and obesity. Insulin receptor signaling through AKT and FOXO has important metabolic effects that have traditionally been ascribed to regulation of gene expression. However, whether all the metabolic effects of FOXO arise from its regulation of prot...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2018.08.003
更新日期:2018-11-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2019.05.004
更新日期:2019-07-01 00:00:00
abstract:OBJECTIVE:Adaptive thermogenesis, which is partly mediated by sympathetic input on brown adipose tissue (BAT), is a mechanism of heat production that confers protection against prolonged cold exposure. Various endogenous stimuli, for example, norepinephrine and FGF-21, can also promote the conversion of inguinal white ...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101052
更新日期:2020-11-01 00:00:00
abstract:OBJECTIVE:The C57Bl/6J (Bl/6J) mouse is the most widely used strain in metabolic research. This strain carries a mutation in nicotinamide nucleotide transhydrogenase (Nnt), a mitochondrial enzyme involved in NADPH production, which has been suggested to lead to glucose intolerance and beta-cell dysfunction. However, re...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2014.09.006
更新日期:2014-09-28 00:00:00
abstract:BACKGROUND:Pancreatic β-cells adapt to high metabolic demand by expanding their β-cell mass and/or enhancing insulin secretion to maintain glucose homeostasis. Type 2 diabetes (T2D) is typically characterized by β-cell decompensation. SCOPE OF THE REVIEW:The current review focuses on summarizing the "omics" and "epi-o...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2019.06.003
更新日期:2019-09-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2014.12.005
更新日期:2014-12-19 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.02.001
更新日期:2016-02-13 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101116
更新日期:2021-01-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2015.12.006
更新日期:2016-01-14 00:00:00
abstract::The lipin protein family of phosphatidate phosphatases has an established role in triacylglycerol synthesis and storage. Physiological roles for lipin-1 and lipin-2 have been identified, but the role of lipin-3 has remained mysterious. Using lipin single- and double-knockout models we identified a cooperative relation...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2013.11.008
更新日期:2013-11-28 00:00:00
abstract::Obesity is characterized as an excess accumulation of body fat resulting from a positive energy balance. It is the major risk factor for type 2 diabetes (T2D). The evidence for familial aggregation of obesity and its associated metabolic diseases is substantial. To date, about 150 genetic loci identified in genome-wid...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2013.09.002
更新日期:2013-09-25 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2015.11.003
更新日期:2015-11-17 00:00:00
abstract:BACKGROUND:The abundance of energy metabolites is intimately interconnected with the activity of chromatin-modifying enzymes in order to guarantee the finely tuned modulation of gene expression in response to cellular energetic status. Metabolism-induced epigenetic gene regulation is a key molecular axis for the mainte...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2021.101165
更新日期:2021-01-14 00:00:00
abstract::The contribution of mitochondrial dysfunction to insulin resistance is a contentious issue in metabolic research. Recent evidence implicates mitochondrial dysfunction as contributing to multiple forms of insulin resistance. However, some models of mitochondrial dysfunction fail to induce insulin resistance, suggesting...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2014.02.001
更新日期:2014-03-12 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2018.06.002
更新日期:2018-08-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.04.003
更新日期:2016-04-13 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2015.08.002
更新日期:2015-08-18 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2020.101041
更新日期:2020-11-01 00:00:00
abstract::Decreased β-cell mass reflects a shift from quiescence/proliferation into apoptosis, it plays a crucial role in the pathophysiology of diabetes. A major attempt to restore β-cell mass and normoglycemia is to improve β-cell survival. Here we show that switching off the Fas pathway using Fas apoptotic inhibitory protein...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2012.08.006
更新日期:2012-08-17 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2017.06.019
更新日期:2017-07-08 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.09.005
更新日期:2017-12-01 00:00:00
abstract:OBJECTIVE:The enteroendocrine hormone glucagon-like peptide 1 (GLP-1) is an attractive anti-diabetic therapy. Here, we generated a recombinant Lactococcus lactis strain genetically modified to produce GLP-1 and investigated its ability to improve glucose tolerance in mice on chow or high-fat diet (HFD). METHODS:We tra...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.06.006
更新日期:2016-06-22 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2019.08.007
更新日期:2019-11-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.10.015
更新日期:2018-01-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.01.002
更新日期:2020-04-01 00:00:00
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journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2020.01.014
更新日期:2020-08-01 00:00:00