An unbiased silencing screen in muscle cells identifies miR-320a, miR-150, miR-196b, and miR-34c as regulators of skeletal muscle mitochondrial metabolism.

Abstract:

OBJECTIVE:Strategies improving skeletal muscle mitochondrial capacity are commonly paralleled by improvements in (metabolic) health. We and others previously identified microRNAs regulating mitochondrial oxidative capacity, but data in skeletal muscle are limited. Therefore, the present study aimed to identify novel microRNAs regulating skeletal muscle mitochondrial metabolism. METHODS AND RESULTS:We conducted an unbiased, hypothesis-free microRNA silencing screen in C2C12 myoblasts, using >700 specific microRNA inhibitors, and investigated a broad panel of mitochondrial markers. After subsequent validation in differentiated C2C12 myotubes, and exclusion of microRNAs without a human homologue or with an adverse effect on mitochondrial metabolism, 19 candidate microRNAs remained. Human clinical relevance of these microRNAs was investigated by measuring their expression in human skeletal muscle of subject groups displaying large variation in skeletal muscle mitochondrial capacity. CONCLUSION:The results show that that microRNA-320a, microRNA-196b-3p, microRNA-150-5p, and microRNA-34c-3p are tightly related to in vivo skeletal muscle mitochondrial function in humans and identify these microRNAs as targets for improving mitochondrial metabolism.

journal_name

Mol Metab

journal_title

Molecular metabolism

authors

Dahlmans D,Houzelle A,Andreux P,Jörgensen JA,Wang X,de Windt LJ,Schrauwen P,Auwerx J,Hoeks J

doi

10.1016/j.molmet.2017.08.007

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

1429-1442

issue

11

issn

2212-8778

pii

S2212-8778(17)30312-5

journal_volume

6

pub_type

杂志文章
  • Loss of dorsomedial hypothalamic GLP-1 signaling reduces BAT thermogenesis and increases adiposity.

    abstract:OBJECTIVE:Glucagon-like peptide-1 (GLP-1) neurons in the hindbrain densely innervate the dorsomedial hypothalamus (DMH), a nucleus strongly implicated in body weight regulation and the sympathetic control of brown adipose tissue (BAT) thermogenesis. Therefore, DMH GLP-1 receptors (GLP-1R) are well placed to regulate en...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2018.03.008

    authors: Lee SJ,Sanchez-Watts G,Krieger JP,Pignalosa A,Norell PN,Cortella A,Pettersen KG,Vrdoljak D,Hayes MR,Kanoski SE,Langhans W,Watts AG

    更新日期:2018-05-01 00:00:00

  • Surplus fat rapidly increases fat oxidation and insulin resistance in lipodystrophic mice.

    abstract:OBJECTIVE:Surplus dietary fat cannot be converted into other macronutrient forms or excreted, so has to be stored or oxidized. Healthy mammals store excess energy in the form of triacylgycerol (TAG) in lipid droplets within adipocytes rather than oxidizing it, and thus ultimately gain weight. The 'overflow hypothesis' ...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2018.05.006

    authors: Girousse A,Virtue S,Hart D,Vidal-Puig A,Murgatroyd PR,Mouisel E,Sengenès C,Savage DB

    更新日期:2018-07-01 00:00:00

  • Cardiomyocyte glucagon receptor signaling modulates outcomes in mice with experimental myocardial infarction.

    abstract:OBJECTIVE:Glucagon is a hormone with metabolic actions that maintains normoglycemia during the fasting state. Strategies enabling either inhibition or activation of glucagon receptor (Gcgr) signaling are being explored for the treatment of diabetes or obesity. However, the cardiovascular consequences of manipulating gl...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2014.11.005

    authors: Ali S,Ussher JR,Baggio LL,Kabir MG,Charron MJ,Ilkayeva O,Newgard CB,Drucker DJ

    更新日期:2014-11-29 00:00:00

  • Adipose PTEN regulates adult adipose tissue homeostasis and redistribution via a PTEN-leptin-sympathetic loop.

    abstract:OBJECTIVE:Despite the large body of work describing the tumor suppressor functions of Phosphatase and tensin homologue deleted on chromosome ten (PTEN), its roles in adipose homeostasis of adult animals are not yet fully understood. Here, we sought to determine the role of PTEN in whole-body adipose homeostasis. METHO...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2019.09.008

    authors: Huang W,Queen NJ,McMurphy TB,Ali S,Cao L

    更新日期:2019-12-01 00:00:00

  • Ablation of intact hypothalamic and/or hindbrain TrkB signaling leads to perturbations in energy balance.

    abstract:OBJECTIVE:Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), play a paramount role in the central regulation of energy balance. Despite the substantial body of genetic evidence implicating BDNF- or TrkB-deficiency in human obesity, the critical brain region(s) contributing ...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2015.08.002

    authors: Ozek C,Zimmer DJ,De Jonghe BC,Kalb RG,Bence KK

    更新日期:2015-08-18 00:00:00

  • Upregulated ethanolamine phospholipid synthesis by selenoprotein I is required for effective metabolic reprogramming during T cell activation.

    abstract:OBJECTIVE:T cell activation triggers metabolic reprogramming to meet increased demands for energy and metabolites required for cellular proliferation. Ethanolamine phospholipid synthesis has emerged as a regulator of metabolic shifts in stem cells and cancer cells, which led us to investigate its potential role during ...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2021.101170

    authors: Ma C,Hoffmann FW,Marciel MP,Page KE,Williams-Aduja MA,Akana ENL,Gojanovich GS,Gerschenson M,Urschitz J,Moisyadi S,Khadka VS,Rozovsky S,Deng Y,Horgen FD,Hoffmann PR

    更新日期:2021-01-20 00:00:00

  • Deletion of the glucagon receptor gene before and after experimental diabetes reveals differential protection from hyperglycemia.

    abstract:OBJECTIVE:Mice with congenital loss of the glucagon receptor gene (Gcgr-/- mice) remain normoglycemic in insulinopenic conditions, suggesting that unopposed glucagon action is the driving force for hyperglycemia in Type-1 Diabetes Mellitus (T1DM). However, chronic loss of GCGR results in a neomorphic phenotype that inc...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2018.07.012

    authors: Rivero-Gutierrez B,Haller A,Holland J,Yates E,Khrisna R,Habegger K,Dimarchi R,D'Alessio D,Perez-Tilve D

    更新日期:2018-11-01 00:00:00

  • 11β-Hydroxysteroid dehydrogenase-1 is involved in bile acid homeostasis by modulating fatty acid transport protein-5 in the liver of mice.

    abstract::11β-Hydroxysteroid dehydrogenase-1 (11β-HSD1) plays a key role in glucocorticoid receptor (GR) activation. Besides, it metabolizes some oxysterols and bile acids (BAs). The GR regulates BA homeostasis; however, the impact of impaired 11β-HSD1 activity remained unknown. We profiled plasma and liver BAs in liver-specifi...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2014.04.008

    authors: Penno CA,Morgan SA,Rose AJ,Herzig S,Lavery GG,Odermatt A

    更新日期:2014-05-02 00:00:00

  • Pharmacological stimulation of p53 with low-dose doxorubicin ameliorates diet-induced nonalcoholic steatosis and steatohepatitis.

    abstract:OBJECTIVE:Recent reports have implicated the p53 tumor suppressor in the regulation of lipid metabolism. We hypothesized that the pharmacological activation of p53 with low-dose doxorubicin, which is widely used to treat several types of cancer, may have beneficial effects on nonalcoholic fatty liver disease (NAFLD) an...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2017.12.005

    authors: Porteiro B,Fondevila MF,Buque X,Gonzalez-Rellan MJ,Fernandez U,Mora A,Beiroa D,Senra A,Gallego R,Fernø J,López M,Sabio G,Dieguez C,Aspichueta P,Nogueiras R

    更新日期:2018-02-01 00:00:00

  • Skeletal muscle autophagy and mitophagy in endurance-trained runners before and after a high-fat meal.

    abstract:OBJECTIVE:We tested the hypothesis that skeletal muscle of endurance-trained male runners would exhibit elevated autophagy and mitophagy markers, which would be associated with greater metabolic flexibility following a high-fat meal (HFM). METHODS:Muscle biopsies were collected to determine differences in autophagy an...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2017.10.006

    authors: Tarpey MD,Davy KP,McMillan RP,Bowser SM,Halliday TM,Boutagy NE,Davy BM,Frisard MI,Hulver MW

    更新日期:2017-12-01 00:00:00

  • Distinct adipocyte progenitor cells are associated with regional phenotypes of perivascular aortic fat in mice.

    abstract:OBJECTIVE:Perivascular adipose tissue depots around the aorta are regionally distinct and have specific functional properties. Thoracic aorta perivascular adipose tissue (tPVAT) expresses higher levels of thermogenic genes and lower levels of inflammatory genes than abdominal aorta perivascular adipose tissue (aPVAT). ...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2017.12.014

    authors: Tran KV,Fitzgibbons T,Min SY,DeSouza T,Corvera S

    更新日期:2018-03-01 00:00:00

  • Action and therapeutic potential of oxyntomodulin.

    abstract::Oxyntomodulin (OXM) is a peptide hormone released from the gut in post-prandial state that activates both the glucagon-like peptide-1 receptor (GLP1R) and the glucagon receptor (GCGR) resulting in superior body weight lowering to selective GLP1R agonists. OXM reduces food intake and increases energy expenditure in hum...

    journal_title:Molecular metabolism

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmet.2013.12.001

    authors: Pocai A

    更新日期:2013-12-14 00:00:00

  • High-fidelity Glucagon-CreER mouse line generated by CRISPR-Cas9 assisted gene targeting.

    abstract:OBJECTIVE:α-cells are the second most prominent cell type in pancreatic islets and are responsible for producing glucagon to increase plasma glucose levels in times of fasting. α-cell dysfunction and inappropriate glucagon secretion occur in both type 1 and type 2 diabetes. Thus, there is growing interest in studying b...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2017.01.003

    authors: Ackermann AM,Zhang J,Heller A,Briker A,Kaestner KH

    更新日期:2017-01-12 00:00:00

  • Profiling plasma N-Acylethanolamine levels and their ratios as a biomarker of obesity and dysmetabolism.

    abstract:OBJECTIVE:N-acylethanolamines play different roles in energy balance; anandamide (AEA) stimulates energy intake and storage, N-palmitoylethanolamide (PEA) counters inflammation, and N-oleoylethanolamide (OEA) mediates anorectic signals and lipid oxidation. Inconsistencies in the association of plasma N-acylethanolamine...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2018.06.002

    authors: Fanelli F,Mezzullo M,Repaci A,Belluomo I,Ibarra Gasparini D,Di Dalmazi G,Mastroroberto M,Vicennati V,Gambineri A,Morselli-Labate AM,Pasquali R,Pagotto U

    更新日期:2018-08-01 00:00:00

  • Activation of natriuretic peptides and the sympathetic nervous system following Roux-en-Y gastric bypass is associated with gonadal adipose tissues browning.

    abstract:OBJECTIVE:Roux-en-Y gastric bypass (RYGB) is an effective method of weight loss and remediation of type-2 diabetes; however, the mechanisms leading to these improvements are unclear. Additionally, adipocytes within white adipose tissue (WAT) depots can manifest characteristics of brown adipocytes. These 'BRITE/beige' a...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2015.02.006

    authors: Neinast MD,Frank AP,Zechner JF,Li Q,Vishvanath L,Palmer BF,Aguirre V,Gupta RK,Clegg DJ

    更新日期:2015-03-03 00:00:00

  • The AMPK activator R419 improves exercise capacity and skeletal muscle insulin sensitivity in obese mice.

    abstract:OBJECTIVE:Skeletal muscle AMP-activated protein kinase (AMPK) is important for regulating glucose homeostasis, mitochondrial content and exercise capacity. R419 is a mitochondrial complex-I inhibitor that has recently been shown to acutely activate AMPK in myotubes. Our main objective was to examine whether R419 treatm...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2015.06.002

    authors: Marcinko K,Bujak AL,Lally JS,Ford RJ,Wong TH,Smith BK,Kemp BE,Jenkins Y,Li W,Kinsella TM,Hitoshi Y,Steinberg GR

    更新日期:2015-06-15 00:00:00

  • Evidence for a novel functional role of astrocytes in the acute homeostatic response to high-fat diet intake in mice.

    abstract:OBJECTIVE:Introduction of a high-fat diet to mice results in a period of voracious feeding, known as hyperphagia, before homeostatic mechanisms prevail to restore energy intake to an isocaloric level. Acute high-fat diet hyperphagia induces astrocyte activation in the rodent hypothalamus, suggesting a potential role of...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2014.10.001

    authors: Buckman LB,Thompson MM,Lippert RN,Blackwell TS,Yull FE,Ellacott KL

    更新日期:2014-10-16 00:00:00

  • Ceramides are necessary and sufficient for diet-induced impairment of thermogenic adipocytes.

    abstract:OBJECTIVE:Aging and weight gain lead to a decline in brown and beige adipocyte functionality that exacerbates obesity and insulin resistance. We sought to determine whether sphingolipids, such as ceramides, a class of lipid metabolites that accumulate in aging and overnutrition, are sufficient or necessary for the meta...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2020.101145

    authors: Chaurasia B,Ying L,Talbot CL,Maschek JA,Cox J,Schuchman EH,Hirabayashi Y,Holland WL,Summers SA

    更新日期:2020-12-19 00:00:00

  • GPR142 prompts glucagon-like Peptide-1 release from islets to improve β cell function.

    abstract:OBJECTIVE:GPR142 agonists are being pursued as novel diabetes therapies by virtue of their insulin secretagogue effects. But it is undetermined whether GPR142's functions in pancreatic islets are limited to regulating insulin secretion. The current study expands research on its action. METHODS AND RESULTS:We demonstra...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2018.02.008

    authors: Lin HV,Wang J,Wang J,Li W,Wang X,Alston JT,Thomas MK,Briere DA,Syed SK,Efanov AM

    更新日期:2018-05-01 00:00:00

  • Vacuolar protein sorting 13C is a novel lipid droplet protein that inhibits lipolysis in brown adipocytes.

    abstract:OBJECTIVE:Brown adipose tissue (BAT) thermogenesis depends on the mobilization and oxidation of fatty acids from intracellular lipid droplets (LD) within brown adipocytes (BAs); however, the identity and function of LD proteins that control BAT lipolysis remain incomplete. Proteomic analysis of mouse BAT subcellular fr...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2017.10.014

    authors: Ramseyer VD,Kimler VA,Granneman JG

    更新日期:2018-01-01 00:00:00

  • Preadipocytes of obese humans display gender-specific bioenergetic responses to glucose and insulin.

    abstract:BACKGROUND/OBJECTIVES:Although the prevalence of obesity and its associated metabolic disorders is increasing in both sexes, the clinical phenotype differs between men and women, highlighting the need for individual treatment options. Mitochondrial dysfunction in various tissues, including white adipose tissue (WAT), h...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2018.11.006

    authors: Keuper M,Berti L,Raedle B,Sachs S,Böhm A,Fritsche L,Fritsche A,Häring HU,Hrabě de Angelis M,Jastroch M,Hofmann SM,Staiger H

    更新日期:2019-02-01 00:00:00

  • Gut microbiota and immune crosstalk in metabolic disease.

    abstract:BACKGROUND:Gut microbiota is considered as a major regulator of metabolic disease. This reconciles the notion of metabolic inflammation and the epidemic development of the disease. In addition to evidence showing that a specific gut microbiota characterizes patients with obesity, type 2 diabetes, and hepatic steatosis,...

    journal_title:Molecular metabolism

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmet.2016.05.016

    authors: Burcelin R

    更新日期:2016-06-06 00:00:00

  • Chronic hyperglycemia downregulates GLP-1 receptor signaling in pancreatic β-cells via protein kinase A.

    abstract:OBJECTIVE:Glucagon-like peptide 1 (GLP-1) enhances insulin secretion and protects β-cell mass. Diabetes therapies targeting the GLP-1 receptor (GLP-1R), expressed in numerous tissues, have diminished dose-response in patients with type 2 diabetes compared with healthy human controls. The aim of this study was to determ...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2015.01.010

    authors: Rajan S,Dickson LM,Mathew E,Orr CM,Ellenbroek JH,Philipson LH,Wicksteed B

    更新日期:2015-02-03 00:00:00

  • Mitochondrial Dynamin-Related Protein 1 (DRP1) translocation in response to cerebral glucose is impaired in a rat model of early alteration in hypothalamic glucose sensing.

    abstract:OBJECTIVE:Hypothalamic glucose sensing (HGS) initiates insulin secretion (IS) via a vagal control, participating in energy homeostasis. This requires mitochondrial reactive oxygen species (mROS) signaling, dependent on mitochondrial fission, as shown by invalidation of the hypothalamic DRP1 protein. Here, our objective...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2018.11.007

    authors: Desmoulins L,Chrétien C,Paccoud R,Collins S,Cruciani-Guglielmacci C,Galinier A,Liénard F,Quinault A,Grall S,Allard C,Fenech C,Carneiro L,Mouillot T,Fournel A,Knauf C,Magnan C,Fioramonti X,Pénicaud L,Leloup C

    更新日期:2019-02-01 00:00:00

  • Metabolically phenotyped pancreatectomized patients as living donors for the study of islets in health and diabetes.

    abstract:BACKGROUND:The availability of human pancreatic islets with characteristics closely resembling those present in vivo is instrumental for ex vivo studies in diabetes research. SCOPE OF REVIEW:In this review we propose metabolically phenotyped surgical patients as a novel source of pancreatic tissue for islet research. ...

    journal_title:Molecular metabolism

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmet.2019.06.006

    authors: Barovic M,Distler M,Schöniger E,Radisch N,Aust D,Weitz J,Ibberson M,Schulte AM,Solimena M

    更新日期:2019-09-01 00:00:00

  • The taming of PARP1 and its impact on NAD+ metabolism.

    abstract:BACKGROUND:Poly-ADP-ribose polymerases (PARPs) are key mediators of cellular stress response. They are intimately linked to cellular metabolism through the consumption of NAD+. PARP1/ARTD1 in the nucleus is the major NAD+ consuming activity and plays a key role in maintaining genomic integrity. SCOPE OF REVIEW:In this...

    journal_title:Molecular metabolism

    pub_type: 杂志文章,评审

    doi:10.1016/j.molmet.2020.01.014

    authors: Hurtado-Bagès S,Knobloch G,Ladurner AG,Buschbeck M

    更新日期:2020-08-01 00:00:00

  • Melanocortin-3 receptors in the limbic system mediate feeding-related motivational responses during weight loss.

    abstract:OBJECTIVE:Appetitive responses to weight loss are mediated by a nutrient-sensing neural network comprised of melanocortin neurons. The role of neural melanocortin-3 receptors (MC3R) in mediating these responses is enigmatic. Mc3r knockout mice exhibit a paradoxical phenotype of obesity and reduced feeding-related behav...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2016.05.002

    authors: Mavrikaki M,Girardet C,Kern A,Faruzzi Brantley A,Miller CA,Macarthur H,Marks DL,Butler AA

    更新日期:2016-05-12 00:00:00

  • Altered ghrelin secretion in mice in response to diet-induced obesity and Roux-en-Y gastric bypass.

    abstract::The current study examined potential mechanisms for altered circulating ghrelin levels observed in diet-induced obesity (DIO) and following weight loss resulting from Roux-en-Y gastric bypass (RYGB). We hypothesized that circulating ghrelin levels were altered in obesity and after weight loss through changes in ghreli...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2014.07.009

    authors: Uchida A,Zechner JF,Mani BK,Park WM,Aguirre V,Zigman JM

    更新日期:2014-08-01 00:00:00

  • Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity.

    abstract:OBJECTIVE/METHODS:DNA methylation plays an important role in obesity and related metabolic complications. We examined genome-wide DNA promoter methylation along with mRNA profiles in paired samples of human subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) from non-obese vs. obese individuals...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2016.11.003

    authors: Keller M,Hopp L,Liu X,Wohland T,Rohde K,Cancello R,Klös M,Bacos K,Kern M,Eichelmann F,Dietrich A,Schön MR,Gärtner D,Lohmann T,Dreßler M,Stumvoll M,Kovacs P,DiBlasio AM,Ling C,Binder H,Blüher M,Böttcher Y

    更新日期:2016-11-16 00:00:00

  • Single-cell transcriptomics of human islet ontogeny defines the molecular basis of β-cell dedifferentiation in T2D.

    abstract:OBJECTIVE:Dedifferentiation of pancreatic β-cells may reduce islet function in type 2 diabetes (T2D). However, the prevalence, plasticity and functional consequences of this cellular state remain unknown. METHODS:We employed single-cell RNAseq to detail the maturation program of α- and β-cells during human ontogeny. W...

    journal_title:Molecular metabolism

    pub_type: 杂志文章

    doi:10.1016/j.molmet.2020.101057

    authors: Avrahami D,Wang YJ,Schug J,Feleke E,Gao L,Liu C,HPAP Consortium.,Naji A,Glaser B,Kaestner KH

    更新日期:2020-12-01 00:00:00