Evidence map›Paper›PMID 31541353›Full record

ArticleMolecular and cellular biochemistry2020

Insulin-induced de novo lipid synthesis occurs mainly via mTOR-dependent regulation of proteostasis of SREBP-1c.

Qingming Dong, Gipsy Majumdar, Robert N O'Meally, Robert N Cole, Marshall B Elam, Rajendra Raghow

Abstract read
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In one paragraph

Article in Molecular and cellular biochemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

23 citing papers in PubMed, 34 citations in OpenAlex.

  1. Trial
  2. Impaired mTOR/SREBP1-Mediated Lipogenesis as a Mechanism of Hepatic Glycogen Accumulation in a Carnivorous Fish Model, Largemouth Bass (Micropterus salmoides).FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  18. The central moTOR of metabolism.Developmental cell · 2022
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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

6 authors at 3 institutions in 1 country.

Qingming DongDepartment of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
Gipsy MajumdarResearch Service (151), Department of Veterans Affairs Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA.
Robert N O'MeallyMass Spectrometry and Proteomics Facility, Johns Hopkins School of Medicine, 733 Broadway Street, Suite 371 MRB, Baltimore, MD, 21205, USA.
Robert N ColeMass Spectrometry and Proteomics Facility, Johns Hopkins School of Medicine, 733 Broadway Street, Suite 371 MRB, Baltimore, MD, 21205, USA.
Marshall B ElamDepartment of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
Rajendra RaghowDepartment of Pharmacology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, USA. rraghow@uthsc.edu.
University of Tennessee Health Science Center · USJohns Hopkins Medicine · USJohns Hopkins University · US

Funding

Department of Veterans Affairs Merit Review Grants 1I01BX002409
6 · The paper itself

Abstract

Insulin stimulates de novo lipid synthesis in the liver and in cultured hepatocytes via its ability to activate sterol regulatory element-binding protein 1c (SREBP-1c). Although PI3K-AKT-mTORC1-p70S6K-signaling kinases are known to drive feed-forward expression of SREBP-1c, the identity of the phosphorylated amino acid residue(s) putatively involved in insulin-stimulated de novo lipogenesis remains elusive. We obtained in silico and mass spectrometry evidence, that was combined with siRNA strategies, to discover that insulin-induced phosphorylation of serine 418, serine 419, and serine 422 in rat SREBP-1c was most likely mediated by p70S6 kinase. Here, for the first time, we show that insulin-induced phosphorylation of these 3 serine residues mainly impinged on the mechanisms of proteostasis of both full-length and mature SREBP-1c in the McArdle-RH7777 hepatoma cells. Consistent with this conclusion, nascent SREBP-1c, substituted with phosphomimetic aspartic acid residues at these 3 sites, was resistant to proteasomal degradation. As a consequence, endoplasmic reticulum to Golgi migration and proteolytic maturation of pSREBP-1c was significantly enhanced which led to increased accumulation of mature nSREBP-1c, even in the absence of insulin. Remarkably, aspartic acid substitutions at S418, S419 and S422 also protected the nascent SREBP-1c from ubiquitin-mediated proteasome degradation thus increasing its steady-state levels and transactivation potential in the nucleus. These complementary effects of p70S6K-mediated phosphorylation on proteostasis of pSREBP-1c were necessary and sufficient to account for insulin's ability to enhance transcription of genes controlling de novo lipogenesis in hepatocytes.

Indexed as

LipogenesisProteostasisCell Line, TumorHepatocytesHumansLipidsRibosomal Protein S6 Kinases, 70-kDaSterol Regulatory Element Binding Protein 1TOR Serine-Threonine KinasesTranscription, GeneticLipidsMTOR protein, humanRibosomal Protein S6 Kinases, 70-kDaSREBF1 protein, humanSterol Regulatory Element Binding Protein 1TOR Serine-Threonine KinasesMass spectrometryMechanistic target of rapamycin (mTOR)PhosphorylationProteasome degradationSREBP-1cUbiquitin

Identifiers

PMID31541353
OpenAlexW2974570242

What OpenQuestion holds

Textmetadata
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.