Evidence map›Paper›PMID 26824363›Full record

ArticleEndocrinology2016

Effect of Leptin Replacement on PCSK9 in ob/ob Mice and Female Lipodystrophic Patients.

Amy E Levenson, Mary E Haas, Ji Miao, Rebecca J Brown, Sarah D de Ferranti, Ranganath Muniyappa, Sudha B Biddinger

Open access · bronzeAbstract read
In one paragraph

Article in Endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

9 citing papers in PubMed, 20 citations in OpenAlex.

  1. Navigating Lipodystrophy: Insights from Laminopathies and Beyond.International journal of molecular sciences · 2024
    Review
  2. Prognostic Value ofCancers · 2024
    Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. PCSK9 targets important for lipid metabolism.Clinical research in cardiology supplements · 2017
    Review
  9. Tumour biology of obesity-related cancers: understanding the molecular concept for better diagnosis and treatment.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Review
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

7 authors at 3 institutions in 1 country.

Amy E LevensonDivision of Endocrinology (A.E.L., M.E.H., J.M., S.B.B.), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Diabetes, Endocrinology, and Obesity Branch (R.J.B., R.M.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Cardiology (S.D.d.F.), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Mary E HaasDivision of Endocrinology (A.E.L., M.E.H., J.M., S.B.B.), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Diabetes, Endocrinology, and Obesity Branch (R.J.B., R.M.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Cardiology (S.D.d.F.), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Ji MiaoDivision of Endocrinology (A.E.L., M.E.H., J.M., S.B.B.), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Diabetes, Endocrinology, and Obesity Branch (R.J.B., R.M.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Cardiology (S.D.d.F.), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Rebecca J BrownDivision of Endocrinology (A.E.L., M.E.H., J.M., S.B.B.), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Diabetes, Endocrinology, and Obesity Branch (R.J.B., R.M.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Cardiology (S.D.d.F.), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Sarah D de FerrantiDivision of Endocrinology (A.E.L., M.E.H., J.M., S.B.B.), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Diabetes, Endocrinology, and Obesity Branch (R.J.B., R.M.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Cardiology (S.D.d.F.), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Ranganath MuniyappaDivision of Endocrinology (A.E.L., M.E.H., J.M., S.B.B.), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Diabetes, Endocrinology, and Obesity Branch (R.J.B., R.M.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Cardiology (S.D.d.F.), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Sudha B BiddingerDivision of Endocrinology (A.E.L., M.E.H., J.M., S.B.B.), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Diabetes, Endocrinology, and Obesity Branch (R.J.B., R.M.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; and Department of Cardiology (S.D.d.F.), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Harvard University · USNational Institutes of Health · USBoston Children's Hospital · US

Funding

Pathogenesis of Dyslipidemia and Atherosclerosis in the Diabetic StateR01HL109650 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI BIDDINGER, SUDHA B · 2011 to 2024
$7.2M
CAREER DEVELOPMENT IN DIABETES RESEARCH FOR PEDIATRIC ENDOCRINOLOGISTSK12DK094721 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI LAFFEL, LORI M, WHITE, MORRIS F. · 2011 to 2021
$6.3M
Molecular and Clinical Studies of Insulin ResistanceZIADK047050 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI BROWN, REBECCA · 2009 to 2025
$6.1M
Clinical utility of leptin therapy in syndromic forms of insulin resistance.ZIADK047052 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI BROWN, REBECCA · 2009 to 2025
$5.5M
Insulin Regulation of Liver X Receptor in Normal and Insulin Resistant StatesK99DK100539 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI MIAO, JI · 2013 to 2014
$180k
Intramural NIH HHSNHLBI NIH HHS R01 HL109650NHLBI NIH HHS R01HL109650-05NIDDK NIH HHS 5K12DK094721-05NIDDK NIH HHS K12 DK094721NIDDK NIH HHS K99 DK100539NIDDK NIH HHS K99DK100539-02NIDDK NIH HHS L40 DK065607
6 · The paper itself

Abstract

Leptin treatment has beneficial effects on plasma lipids in patients with lipodystrophy, but the underlying mechanism is unknown. Proprotein convertase subtilisin/kexin type 9 (PCSK9) decreases low-density lipoprotein (LDL) clearance, promotes hypercholesterolemia, and has recently emerged as a novel therapeutic target. To determine the effect of leptin on PCSK9, we treated male and female ob/ob mice with leptin for 4 days via sc osmotic pumps (∼24 μg/d). Leptin reduced body weight and food intake in all mice, but the effects of leptin on plasma PCSK9 and lipids differed markedly between the sexes. In male mice, leptin suppressed PCSK9 but had no effect on plasma triglycerides or cholesterol. In female mice, leptin suppressed plasma triglycerides and cholesterol but had no effect on plasma PCSK9. In parallel, we treated female lipodystrophic patients (8 females, ages 5-23 y) with sc metreleptin injections (∼4.4 mg/d) for 4-6 months. In this case, leptin reduced plasma PCSK9 by 26% (298 ± 109 vs 221 ± 102 ng/mL; n = 8; P = .008), and the change in PCSK9 was correlated with a decrease in LDL cholesterol (r(2) = 0.564, P = .03). In summary, in leptin-deficient ob/ob mice, the effects of leptin on PCSK9 and plasma lipids appeared to be independent of one another and strongly modified by sex. On the other hand, in lipodystrophic females, leptin treatment reduced plasma PCSK9 in parallel with LDL cholesterol.

Indexed as

AdolescentAnimalsBlotting, WesternChildChild, PreschoolCholesterolCholesterol, LDLEnzyme-Linked Immunosorbent AssayFemaleGene ExpressionHumansLeptinLipodystrophyLiverMaleMice, ObeseCholesterolCholesterol, LDLLeptinPcsk9 protein, mouseProprotein Convertase 9Proprotein ConvertasesSerine EndopeptidasesTriglycerides

Identifiers

PMID26824363
PMCPMC4816729
OpenAlexW2273429777

What OpenQuestion holds

Texttitle and abstract
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.