Evidence map›Paper›PMID 18171433›Full record

ReviewActa physiologica (Oxford, England)2008

RNAi screens reveal novel metabolic regulators: RIP140, MAP4k4 and the lipid droplet associated fat specific protein (FSP) 27.

V Puri, J V Virbasius, A Guilherme, M P Czech

Open access · greenAbstract readReview
In one paragraph

Review in Acta physiologica (Oxford, England), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
4.3field-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

34 citing papers in PubMed, 65 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. Observational
  7. Article
  8. New targets to treat obesity and the metabolic syndrome.European journal of pharmacology · 2015
    Review
  9. Article
  10. Downregulation of RIP140 in hepatocellular carcinoma promoted the growth and migration of the cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Crystallization and preliminary X-ray crystallographic studies of the CIDE-N domain of CIDE-3.Acta crystallographica. Section F, Structural biology and crystallization communications · 2013
    Article
  17. Fasting regulates FSP27 expression in the liver.Journal of lipid research · 2013
    Article
  18. Article
  19. Review
  20. Lipid droplets and cellular lipid metabolism.Annual review of biochemistry · 2012
    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

4 authors at 1 institution in 1 country.

V PuriProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
J V Virbasius
A Guilherme
M P Czech
University of Massachusetts Chan Medical School · US

Funding

Diabetes Genome Anatomy Project (DGAP)R01DK060837 · NIDDK · JOSLIN DIABETES CENTER · PI KAHN, C RONALD · 2002 to 2006
$15.9M
SUBCELLULAR LOCALIZATION OF PI 3-KINASE SIGNALINGP01DK060564 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI FOGARTY, KEVIN EDWARD · 2001 to 2011
$13.9M
Insulin Signaling and Metabolic Regulation in AdipocytesR37DK030898 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI CZECH, MICHAEL P · 1996 to 2021
$7.2M
Insulin Signaling and Metabolic Regulation in AdipocytesR01DK030898 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI CZECH, MICHAEL P · 1986 to 2011
$2.7M
NIDDK NIH HHS DK30898NIDDK NIH HHS DK325220NIDDK NIH HHS DK60564NIDDK NIH HHS DK60837-03NIDDK NIH HHS P01 DK060564NIDDK NIH HHS R01 DK030898NIDDK NIH HHS R01 DK060837NIDDK NIH HHS R37 DK030898
6 · The paper itself

Abstract

Adipose tissue modulates whole body metabolism and insulin sensitivity by controlling circulating lipid levels and producing molecules that can regulate fatty acid metabolism in such tissues as muscle and liver. We have developed RNA interference (RNAi) screens to identify genes in cultured adipocytes that regulate insulin signalling and key metabolic pathways. These short interfering RNA (siRNA)-based screens identified the transcriptional corepressor receptor interacting protein 140 (RIP140) (J Clin Invest 116: 125, 2006) and the mitogen-activated protein kinase (MAP4k4) (Proc Natl Acad Sci USA 103: 2087, 2006) as negative regulators of insulin-responsive hexose uptake and oxidative metabolism. Gene expression profiling revealed that RIP140 depletion upregulates the expression of clusters of genes in the pathways of glucose uptake, glycolysis, tricarboxylic acid cycle, fatty acid oxidation, mitochondrial biogenesis and oxidative phosphorylation. RIP140-null mice resist weight gain on a high-fat diet and display enhanced glucose tolerance. MAP4k4 depletion in adipocytes increases many of the RIP140-sensitive genes, increases adipogenesis and mediates some actions of tumour necrosis factor-alpha (TNF-alpha). Remarkably, another hit in our RNAi screens was fat specific protein 27 (FSP27), a highly expressed isoform of Cidea. We discovered that FSP27 unexpectedly associates specifically with lipid droplets and regulates fat storage. We conclude that RIP140, MAP4k4 and the novel lipid droplet protein FSP27 are powerful regulators of adipose tissue metabolism and are potential therapeutic targets for controlling metabolic disease. The discovery of these novel proteins validates the power of RNAi screening for discovery of new therapeutic approaches to type 2 diabetes and obesity.

Indexed as

RNA InterferenceAdaptor Proteins, Signal TransducingAdipocytesAdipogenesisAnimalsHumansInsulinIntracellular Signaling Peptides and ProteinsMiceNuclear ProteinsNuclear Receptor Interacting Protein 1ProteinsProtein Serine-Threonine KinasesSignal TransductionAdaptor Proteins, Signal Transducingfat-specific protein 27, mouseInsulinIntracellular Signaling Peptides and ProteinsMAP4K4 protein, humanNRIP1 protein, humanNuclear ProteinsNuclear Receptor Interacting Protein 1ProteinsProtein Serine-Threonine Kinases

Identifiers

PMID18171433
PMCPMC2880506
OpenAlexW1956492036

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.