Evidence map›Paper›PMID 25199621›Full record

ArticleInternational journal of obesity (2005)2015

Leptin administration activates irisin-induced myogenesis via nitric oxide-dependent mechanisms, but reduces its effect on subcutaneous fat browning in mice.

A Rodríguez, S Becerril, L Méndez-Giménez, B Ramírez, N Sáinz, V Catalán, J Gómez-Ambrosi, G Frühbeck

Abstract read
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In one paragraph

Article in International journal of obesity (2005), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

70 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.

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  9. Exerkines and myokines in aging sarcopenia.Frontiers in endocrinology · 2025
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10 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

A Rodríguez1] Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain [2] CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Pamplona, Spain.
S Becerril1] Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain [2] CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Pamplona, Spain.
L Méndez-Giménez1] Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain [2] CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Pamplona, Spain.
B Ramírez1] Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain [2] CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Pamplona, Spain.
N SáinzMetabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.
V Catalán1] Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain [2] CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Pamplona, Spain.
J Gómez-Ambrosi1] Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain [2] CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Pamplona, Spain.ORCID 0000000156011604
G Frühbeck1] Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain [2] CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Pamplona, Spain [3] Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, Spain.
Instituto de Salud Carlos III · ESClinica Universidad de Navarra · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

unlabelledBACKGROUND/OBJETIVES: Obese leptin-deficient ob/ob mice exhibit high adiposity and reduced muscle mass with leptin replacement promoting weight loss and inducing muscle accretion through PGC-1α-dependent mechanisms. Our aim was to analyze in vivo and in vitro the effect of leptin on FNDC5, a novel PGC-1α-dependent myokine that is synthesized and cleaved to form irisin that induces white adipose browning. METHODS/

resultsTwelve-week-old male wild-type and ob/ob mice were divided in three groups as follows: control, leptin-treated (1 mg kg(-1) day(-1)) and pair-fed. Leptin administration was associated with increased gastrocnemius weight and cell surface area, higher Pgc1a and Fndc5 transcript levels and a slight increase in circulating irisin. Leptin upregulated Fndc5 expression through nitric oxide (NO)-dependent mechanisms in murine C2C12 myocytes and stimulated both basal and irisin-stimulated myogenesis, as evidenced by increased myocyte cell proliferation, higher myogenin and myonectin transcript levels together with lower mRNA expression of myostatin and dystrophin and the muscle atrophy-related factors MuRF1 and MAFbx. Interestingly, leptin downregulated Fndc5 expression in a NO-independent manner in murine differentiated subcutaneous adipocytes. Furthermore, leptin prevented the irisin-induced upregulation of both brown (Ucp1 and Cidec) and beige (Tmem26) adipocyte-specific genes and the increase in uncoupling protein-1-positive cells.

conclusionsTaken together, our results provide evidence for a regulatory role of leptin on FNDC5/irisin, favoring muscle accretion but reducing fat browning.

Indexed as

3T3-L1 CellsAdipose Tissue, BrownAnimalsCells, CulturedFibronectinsGene ExpressionLeptinMaleMiceMuscle, SkeletalNitric OxideObesityPigments, BiologicalSubcutaneous Fat, AbdominalTranscription FactorsUp-RegulationFibronectinsFNDC5 protein, mouseLeptinNitric OxidePigments, BiologicalTranscription Factors

Identifiers

PMID25199621
OpenAlexW1969409088

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.