Evidence map›Paper›PMID 39420421›Full record

ArticleObesity (Silver Spring, Md.)2024

Sustained caloric restriction potentiates insulin action by activating prostacyclin synthase.

Carmen Merali, Connor Quinn, Kim M Huffman, Carl F Pieper, Jonathan S Bogan, Carlos A Barrero, Salim Merali

Abstract read
In one paragraph

Article in Obesity (Silver Spring, Md.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

7 authors.

Carmen MeraliTemple University School of Pharmacy, Philadelphia, Pennsylvania, USA.
Connor QuinnTemple University School of Pharmacy, Philadelphia, Pennsylvania, USA.
Kim M HuffmanDuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Carl F PieperDuke Center for Aging and Human Development, Duke University School of Medicine, Durham, North Carolina, USA.
Jonathan S BoganSection of Endocrinology and Metabolism, Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA.ORCID https://orcid.org/0000-0001-6463-8466
Carlos A BarreroTemple University School of Pharmacy, Philadelphia, Pennsylvania, USA.
Salim MeraliTemple University School of Pharmacy, Philadelphia, Pennsylvania, USA.ORCID https://orcid.org/0000-0002-0280-5289

Funding

ENHANCING THE CALERIE NETWORK TO ADVANCE AGING BIOLOGYR33AG070455 · NIA · DUKE UNIVERSITY · PI KIM M. HUFFMAN, WILLIAM E KRAUS · 2021 to 2026
$4.0M
Vesicle Translocation and the Metabolic SyndromeR01DK129466 · NIDDK · YALE UNIVERSITY · PI BOGAN, JONATHAN · 2022 to 2025
$2.0M
Adipose Tissue Carbonylome and Sustained Calorie RestrictionR21AG064300 · NIA · TEMPLE UNIV OF THE COMMONWEALTH · PI MERALI, SALIM · 2019 to 2020
$436k
NIA NIH HHS R21 AG064300NIA NIH HHS R33 AG070455NIDDK NIH HHS R01 DK129466NIH HHS R01DK129466NIH HHS R21 AG06430NIH HHS R33-AG070455
6 · The paper itself

Abstract

objectiveCaloric restriction (CR) is known to enhance insulin sensitivity and reduce the risk of metabolic disorders; however, its molecular mechanisms are not fully understood. This study aims to elucidate specific proteins and pathways responsible for these benefits.

methodsWe examined adipose tissue from participants in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE 2) study, comparing proteomic profiles from individuals after 12 and 24 months of CR with baseline and an ad libitum group. Biochemical and cell-specific physiological approaches complemented these analyses.

resultsOur data revealed that CR upregulates prostacyclin synthase (PTGIS) in adipose tissue, an enzyme crucial for producing prostacyclin (PGI2). PGI2 improves the ability of insulin to stimulate the tether-containing UBX domain for GLUT4 (TUG) cleavage pathway, which is essential for glucose uptake regulation. Additionally, iloprost, a PGI2 analog, was shown to increase insulin receptor density on cell membranes, increasing glucose uptake in human adipocytes. CR also reduces carbonylation of GLUT4, a modification that is detrimental to GLUT4 function.

conclusionsCR enhances insulin sensitivity by promoting PTGIS expression and stimulating the TUG cleavage pathway, leading to increased GLUT4 translocation to the cell surface and decreased GLUT4 carbonylation. These findings shed light on the complex molecular mechanisms through which CR favorably impacts insulin sensitivity and metabolic health.

Indexed as

Caloric RestrictionCytochrome P-450 Enzyme SystemGlucose Transporter Type 4InsulinInsulin ResistanceAdipocytesAdipose TissueAdultEpoprostenolFemaleGlucoseHumansIntramolecular OxidoreductasesMaleMiddle AgedProteomicsCytochrome P-450 Enzyme SystemEpoprostenolGlucoseGlucose Transporter Type 4InsulinIntramolecular Oxidoreductasesprostacyclin synthetaseSLC2A4 protein, human

Identifiers

PMID39420421
PMCPMC12034231

What OpenQuestion holds

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LicenceTDM
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.