Evidence map›Paper›PMID 39171528›Full record

ArticleJCI insight2024

High-fat and high-carbohydrate diets increase bone fragility through TGF-β-dependent control of osteocyte function.

Neha S Dole, Andrés Betancourt-Torres, Serra Kaya, Yoshihiro Obata, Charles A Schurman, Jihee Yoon, Cristal S Yee, Vivek Khanal, Clarissa Aguirre Luna, Madeline Carroll and 4 more

Abstract read
In one paragraph

Article in JCI insight, 2024. 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
–field-weighted citation impact
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.

  1. Diets Differently Affect Bone Health: Murine Models.International journal of molecular sciences · 2026
    Article
  2. Article
  3. Alzheimer's Disease Risk Factor APOE4 Exerts Dimorphic Effects on Female Bone.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
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

14 authors.

Neha S DoleDepartment of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA.
Andrés Betancourt-TorresDepartment of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA.
Serra KayaDepartment of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA.
Yoshihiro ObataDepartment of Mechanical Engineering, University of Utah, Salt Lake City, Utah, USA.
Charles A SchurmanDepartment of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA.
Jihee YoonDepartment of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA.
Cristal S YeeDepartment of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA.
Vivek KhanalDepartment of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock Arkansas, USA.
Clarissa Aguirre LunaDepartment of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA.
Madeline CarrollDepartment of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock Arkansas, USA.
Jennifer J SalinasDepartment of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA.
Elizabeth MiclauDepartment of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA.
Claire AcevedoDepartment of Mechanical Engineering, University of Utah, Salt Lake City, Utah, USA.
Tamara AllistonDepartment of Orthopaedic Surgery, University of California, San Francisco, San Francisco, California, USA.

Funding

Understanding the Negative Prognostic Impact of Intraosseous Focal Lesions in Multiple MyelomaP20GM125503 · NIGMS · UNIV OF ARKANSAS FOR MED SCIS · PI Jesus Delgado-Calle · 2018 to 2026
$23.0M
The mechanistic control of bone quality and joint crosstalk by osteocytesR01DE019284 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HERNANDEZ, CHRISTOPHER JOHN · 2009 to 2024
$7.6M
Skeletal Biology and Biomechanics (SBB) CoreP30AR075055 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Wenhan Chang · 2019 to 2026
$7.1M
Unraveling the role of osteocytes in metabolic dysfunction associated with obesityK01DK129404 · NIDDK · UNIV OF ARKANSAS FOR MED SCIS · PI DOLE, NEHA · 2021 to 2025
$706k
NIAMS NIH HHS P30 AR075055NIDCR NIH HHS R01 DE019284NIDDK NIH HHS K01 DK129404NIGMS NIH HHS P20 GM125503
6 · The paper itself

Abstract

Obesity can increase the risk of bone fragility, even when bone mass is intact. This fragility stems from poor bone quality, potentially caused by deficiencies in bone matrix material properties. However, cellular and molecular mechanisms leading to obesity-related bone fragility are not fully understood. Using male mouse models of obesity, we discovered TGF-β signaling plays a critical role in mediating the effects of obesity on bone. High-carbohydrate and high-fat diets increase TGF-β signaling in osteocytes, which impairs their mitochondrial function, increases cellular senescence, and compromises perilacunar/canalicular remodeling and bone quality. By specifically inhibiting TGF-β signaling in mouse osteocytes, some of the negative effects of high-fat and high-carbohydrate diets on bones, including the lacunocanalicular network, perilacunar/canalicular remodeling, senescence, and mechanical properties such as yield stress, were mitigated. DMP1-Cre-mediated deletion of TGF-β receptor II also blunted adverse effects of high-fat and high-carbohydrate diets on energy balance and metabolism. These findings suggest osteocytes are key in controlling bone quality in response to high-fat and high-carbohydrate diets. Calibrating osteocyte function could mitigate bone fragility associated with metabolic diseases while reestablishing energy balance.

Indexed as

Diet, High-FatObesityOsteocytesTransforming Growth Factor betaAnimalsBone and BonesBone DensityBone RemodelingDietary CarbohydratesDisease Models, AnimalMaleMiceMice, Inbred C57BLReceptor, Transforming Growth Factor-beta Type IISignal TransductionDietary CarbohydratesReceptor, Transforming Growth Factor-beta Type IITgfbr2 protein, mouseTransforming Growth Factor betaBone biologyObesity

Identifiers

PMID39171528
PMCPMC11343608

What OpenQuestion holds

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LicenceCC BY
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.