Evidence map›Paper›PMID 26487675›Full record

ArticleThe Journal of endocrinology2015

Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss.

Russell T Turner, Michael Dube, Adam J Branscum, Carmen P Wong, Dawn A Olson, Xiaoying Zhong, Mercedes F Kweh, Iske V Larkin, Thomas J Wronski, Clifford J Rosen and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.9field-weighted citation impact, top 31% 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

12 citing papers in PubMed, 14 citations in OpenAlex.

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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

12 authors at 1 institution in 1 country.

Russell T TurnerSkeletal Biology LaboratorySchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USACenter for Healthy Aging ResearchOregon State University, Corvallis, Oregon, USADepartment of NeuroscienceMcKnight Brain Institute, University of Florida, Gainesville, Florida, USABiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USADepartment of Physiological SciencesUniversity of Florida, Gainesville, Florida, USADepartment of Large Animal Clinical SciencesUniversity of Florida, Gainesville, Florida, USAMaine Medical Center Research InstituteScarborough, Maine, USA Skeletal Biology LaboratorySchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USACenter for Healthy Aging ResearchOregon State University, Corvallis, Oregon, USADepartment of NeuroscienceMcKnight Brain Institute, University of Florida, Gainesville, Florida, USABiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USADepartment of Physiological SciencesUniversity of Florida, Gainesville, Florida, USADepartment of Large Animal Clinical SciencesUniversity of Florida, Gainesville, Florida, USAMaine Medical Center Research InstituteScarborough, Maine, USA.
Michael DubeSkeletal Biology LaboratorySchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USACenter for Healthy Aging ResearchOregon State University, Corvallis, Oregon, USADepartment of NeuroscienceMcKnight Brain Institute, University of Florida, Gainesville, Florida, USABiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USADepartment of Physiological SciencesUniversity of Florida, Gainesville, Florida, USADepartment of Large Animal Clinical SciencesUniversity of Florida, Gainesville, Florida, USAMaine Medical Center Research InstituteScarborough, Maine, USA.
Adam J BranscumSkeletal Biology LaboratorySchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USACenter for Healthy Aging ResearchOregon State University, Corvallis, Oregon, USADepartment of NeuroscienceMcKnight Brain Institute, University of Florida, Gainesville, Florida, USABiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USADepartment of Physiological SciencesUniversity of Florida, Gainesville, Florida, USADepartment of Large Animal Clinical SciencesUniversity of Florida, Gainesville, Florida, USAMaine Medical Center Research InstituteScarborough, Maine, USA.
Carmen P WongSkeletal Biology LaboratorySchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USACenter for Healthy Aging ResearchOregon State University, Corvallis, Oregon, USADepartment of NeuroscienceMcKnight Brain Institute, University of Florida, Gainesville, Florida, USABiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USADepartment of Physiological SciencesUniversity of Florida, Gainesville, Florida, USADepartment of Large Animal Clinical SciencesUniversity of Florida, Gainesville, Florida, USAMaine Medical Center Research InstituteScarborough, Maine, USA.
Dawn A OlsonSkeletal Biology LaboratorySchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USACenter for Healthy Aging ResearchOregon State University, Corvallis, Oregon, USADepartment of NeuroscienceMcKnight Brain Institute, University of Florida, Gainesville, Florida, USABiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USADepartment of Physiological SciencesUniversity of Florida, Gainesville, Florida, USADepartment of Large Animal Clinical SciencesUniversity of Florida, Gainesville, Florida, USAMaine Medical Center Research InstituteScarborough, Maine, USA.
Xiaoying ZhongSkeletal Biology LaboratorySchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USACenter for Healthy Aging ResearchOregon State University, Corvallis, Oregon, USADepartment of NeuroscienceMcKnight Brain Institute, University of Florida, Gainesville, Florida, USABiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USADepartment of Physiological SciencesUniversity of Florida, Gainesville, Florida, USADepartment of Large Animal Clinical SciencesUniversity of Florida, Gainesville, Florida, USAMaine Medical Center Research InstituteScarborough, Maine, USA.
Mercedes F KwehSkeletal Biology LaboratorySchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USACenter for Healthy Aging ResearchOregon State University, Corvallis, Oregon, USADepartment of NeuroscienceMcKnight Brain Institute, University of Florida, Gainesville, Florida, USABiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USADepartment of Physiological SciencesUniversity of Florida, Gainesville, Florida, USADepartment of Large Animal Clinical SciencesUniversity of Florida, Gainesville, Florida, USAMaine Medical Center Research InstituteScarborough, Maine, USA.
Iske V LarkinSkeletal Biology LaboratorySchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USACenter for Healthy Aging ResearchOregon State University, Corvallis, Oregon, USADepartment of NeuroscienceMcKnight Brain Institute, University of Florida, Gainesville, Florida, USABiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USADepartment of Physiological SciencesUniversity of Florida, Gainesville, Florida, USADepartment of Large Animal Clinical SciencesUniversity of Florida, Gainesville, Florida, USAMaine Medical Center Research InstituteScarborough, Maine, USA.
Thomas J WronskiSkeletal Biology LaboratorySchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USACenter for Healthy Aging ResearchOregon State University, Corvallis, Oregon, USADepartment of NeuroscienceMcKnight Brain Institute, University of Florida, Gainesville, Florida, USABiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USADepartment of Physiological SciencesUniversity of Florida, Gainesville, Florida, USADepartment of Large Animal Clinical SciencesUniversity of Florida, Gainesville, Florida, USAMaine Medical Center Research InstituteScarborough, Maine, USA.
Clifford J RosenSkeletal Biology LaboratorySchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USACenter for Healthy Aging ResearchOregon State University, Corvallis, Oregon, USADepartment of NeuroscienceMcKnight Brain Institute, University of Florida, Gainesville, Florida, USABiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USADepartment of Physiological SciencesUniversity of Florida, Gainesville, Florida, USADepartment of Large Animal Clinical SciencesUniversity of Florida, Gainesville, Florida, USAMaine Medical Center Research InstituteScarborough, Maine, USA.
Satya P KalraSkeletal Biology LaboratorySchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USACenter for Healthy Aging ResearchOregon State University, Corvallis, Oregon, USADepartment of NeuroscienceMcKnight Brain Institute, University of Florida, Gainesville, Florida, USABiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USADepartment of Physiological SciencesUniversity of Florida, Gainesville, Florida, USADepartment of Large Animal Clinical SciencesUniversity of Florida, Gainesville, Florida, USAMaine Medical Center Research InstituteScarborough, Maine, USA.
Urszula T IwaniecSkeletal Biology LaboratorySchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USACenter for Healthy Aging ResearchOregon State University, Corvallis, Oregon, USADepartment of NeuroscienceMcKnight Brain Institute, University of Florida, Gainesville, Florida, USABiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USADepartment of Physiological SciencesUniversity of Florida, Gainesville, Florida, USADepartment of Large Animal Clinical SciencesUniversity of Florida, Gainesville, Florida, USAMaine Medical Center Research InstituteScarborough, Maine, USA Skeletal Biology LaboratorySchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon 97331, USACenter for Healthy Aging ResearchOregon State University, Corvallis, Oregon, USADepartment of NeuroscienceMcKnight Brain Institute, University of Florida, Gainesville, Florida, USABiostatisticsSchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USADepartment of Physiological SciencesUniversity of Florida, Gainesville, Florida, USADepartment of Large Animal Clinical SciencesUniversity of Florida, Gainesville, Florida, USAMaine Medical Center Research InstituteScarborough, Maine, USA urszula.iwaniec@oregonstate.edu.
Oregon State University · US

Funding

Interdisciplinary Study of Marrow Adiposity, Mineral Metabolism & Energy BalanceR24DK092759 · NIDDK · MAINEHEALTH · PI HOROWITZ, MARK C, MACDOUGALD, ORMOND A · 2011 to 2019
$13.0M
The Role of Leptin in Inflammation-Driven Bone LossR01AR060913 · NIAMS · OREGON STATE UNIVERSITY · PI IWANIEC, URSZULA T · 2011 to 2025
$3.5M
NIAMS NIH HHS AR 060913NIAMS NIH HHS R01 AR060913NIDDK NIH HHS R24 DK092759
6 · The paper itself

Abstract

Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin, n=7) or a control vector encoding green fluorescent protein (rAAV-GFP, n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (-4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (-80%), serum leptin (-77%), and serum IGF1 (-34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (P<0.1) in rAAV-GFP-treated rats (13.5 months old) compared to baseline control rats (9 months old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.

Indexed as

AnimalsBody WeightBone DensityFemaleGenetic TherapyHypothalamusInsulin-Like Growth Factor ILeptinObesityRatsRats, Sprague-DawleyWeight LossInsulin-Like Growth Factor ILeptindual energy absorptiometrymicrocomputed tomographyrAAV-Leptinwhite adipose tissue

Identifiers

PMID26487675
PMCPMC4917201
OpenAlexW1749447794

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Registered trials

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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.