Evidence map›Paper›PMID 31767179›Full record

ArticleMolecular metabolism2019

Sex-specific metabolic functions of adipose Lipocalin-2.

Karthickeyan Chella Krishnan, Simon Sabir, Michaël Shum, Yonghong Meng, Rebeca Acín-Pérez, Jennifer M Lang, Raquel R Floyd, Laurent Vergnes, Marcus M Seldin, Brie K Fuqua and 9 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 6% 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

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

  1. Association Of Blood Lipocalin-2 Levels with Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2022
    Pooled it
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  11. Sex Differences in Cochlear Transcriptomes in Horseshoe Bats.Animals : an open access journal from MDPI · 2024
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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

19 authors at 2 institutions in 1 country.

Karthickeyan Chella KrishnanDepartment of Medicine/Division of Cardiology, University of California, Los Angeles, CA, USA. Electronic address: kchellakrishnan@mednet.ucla.edu.
Simon SabirDepartment of Psychology, University of California, Los Angeles, CA, USA.
Michaël ShumDepartment of Medicine/Division of Endocrinology, University of California, Los Angeles, CA, USA.
Yonghong MengDepartment of Medicine/Division of Cardiology, University of California, Los Angeles, CA, USA.
Rebeca Acín-PérezDepartment of Medicine/Division of Endocrinology, University of California, Los Angeles, CA, USA.
Jennifer M LangDepartment of Medicine/Division of Cardiology, University of California, Los Angeles, CA, USA.
Raquel R FloydDepartment of Biology, University of California, Los Angeles, CA, USA.
Laurent VergnesDepartment of Human Genetics, University of California, Los Angeles, CA, USA.
Marcus M SeldinDepartment of Medicine/Division of Cardiology, University of California, Los Angeles, CA, USA.
Brie K FuquaDepartment of Medicine/Division of Cardiology, University of California, Los Angeles, CA, USA.
Dulshan W JayasekeraDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA.
Sereena K NandDepartment of Biology, University of California, Los Angeles, CA, USA.
Diana C AnumDepartment of Integrative Biology and Physiology, University of California, Los Angeles, CA, USA.
Calvin PanDepartment of Medicine/Division of Cardiology, University of California, Los Angeles, CA, USA.
Linsey StilesDepartment of Medicine/Division of Endocrinology, University of California, Los Angeles, CA, USA.
Miklós PéterfyDepartment of Medicine/Division of Cardiology, University of California, Los Angeles, CA, USA; Department of Basic Medical Sciences, Western University of Health Sciences, Pomona, CA, USA.
Karen ReueDepartment of Human Genetics, University of California, Los Angeles, CA, USA.
Marc LiesaDepartment of Medicine/Division of Endocrinology, University of California, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA.
Aldons J LusisDepartment of Medicine/Division of Cardiology, University of California, Los Angeles, CA, USA; Department of Human Genetics, University of California, Los Angeles, CA, USA; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA. Electronic address: JLusis@mednet.ucla.edu.
University of California, Los Angeles · USWestern University of Health Sciences · US

Funding

Sex Differences in the Metabolic SyndromeU54DK120342 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REUE, KAREN · 2018 to 2022
$7.6M
Vascular Biology Training GrantT32HL069766 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 2002 to 2022
$7.4M
NHLBI NIH HHS T32 HL069766NIDDK NIH HHS U54 DK120342
6 · The paper itself

Abstract

objectiveLipocalin-2 (LCN2) is a secreted protein involved in innate immunity and has also been associated with several cardiometabolic traits in both mouse and human studies. However, the causal relationship of LCN2 to these traits is unclear, and most studies have examined only males.

methodsUsing adeno-associated viral vectors we expressed LCN2 in either adipose or liver in a tissue specific manner on the background of a whole-body Lcn2 knockout or wildtype mice. Metabolic phenotypes including body weight, body composition, plasma and liver lipids, glucose homeostasis, insulin resistance, mitochondrial phenotyping, and metabolic cage studies were monitored.

resultsWe studied the genetics of LCN2 expression and associated clinical traits in both males and females in a panel of 100 inbred strains of mice (HMDP). The natural variation in Lcn2 expression across the HMDP exhibits high heritability, and genetic mapping suggests that it is regulated in part by Lipin1 gene variation. The correlation analyses revealed striking tissue dependent sex differences in obesity, insulin resistance, hepatic steatosis, and dyslipidemia. To understand the causal relationships, we examined the effects of expression of LCN2 selectively in liver or adipose. On a Lcn2-null background, LCN2 expression in white adipose promoted metabolic disturbances in females but not males. It acted in an autocrine/paracrine manner, resulting in mitochondrial dysfunction and an upregulation of inflammatory and fibrotic genes. On the other hand, on a null background, expression of LCN2 in liver had no discernible impact on the traits examined despite increasing the levels of circulating LCN2 more than adipose LCN2 expression. The mechanisms underlying the sex-specific action of LCN2 are unclear, but our results indicate that adipose LCN2 negatively regulates its receptor, LRP2 (or megalin), and its repressor, ERα, in a female-specific manner and that the effects of LCN2 on metabolic traits are mediated in part by LRP2.

conclusionsFollowing up on our population-based studies, we demonstrate that LCN2 acts in a highly sex- and tissue-specific manner in mice. Our results have important implications for human studies, emphasizing the importance of sex and the tissue source of LCN2.

Indexed as

Adipose TissueAdiposityAnimalsBody CompositionBody WeightFemaleGlucoseHomeostasisInsulin ResistanceLipidsLipocalin-2MaleMiceMice, Inbred C57BLMice, Inbred StrainsMice, KnockoutGlucoseLipidsLipocalin-2Adipose fibrosisAdipose inflammationDiet-induced obesityInsulin resistanceMitochondrial dysfunctionSex differences

Identifiers

PMID31767179
PMCPMC6812340
OpenAlexW2975985297

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.