Evidence map›Paper›PMID 28580278›Full record

ArticleMolecular metabolism2017

FGF21 does not require adipocyte AMP-activated protein kinase (AMPK) or the phosphorylation of acetyl-CoA carboxylase (ACC) to mediate improvements in whole-body glucose homeostasis.

Emilio P Mottillo, Eric M Desjardins, Andreas M Fritzen, Vito Z Zou, Justin D Crane, Julian M Yabut, Bente Kiens, Derek M Erion, Adhiraj Lanba, James G Granneman and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 8% 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, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Pooled it
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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 6 institutions in 3 countries.

Emilio P MottilloDivision of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, Ontario, L8N 3Z5, Canada.
Eric M DesjardinsDivision of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, Ontario, L8N 3Z5, Canada.
Andreas M FritzenSection of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark.
Vito Z ZouDivision of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, Ontario, L8N 3Z5, Canada.
Justin D CraneDivision of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, Ontario, L8N 3Z5, Canada.
Julian M YabutDivision of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, Ontario, L8N 3Z5, Canada.
Bente KiensSection of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark.
Derek M ErionLiver Disease Research, Takeda Pharmaceuticals, 35 Landsdowne Street, Cambridge, MA, 02139, USA.
Adhiraj LanbaCardiovascular & Metabolic Diseases, Novartis Institute of Biomedical Research, 250 Massachusetts Avenue, Cambridge, MA, 02139, USA.
James G GrannemanWayne State University School of Medicine, Detroit, MI, 48201, USA.
Saswata TalukdarCardiometabolic Diseases, Merck Research Laboratories South San Francisco LLC, 630 Gateway Boulevard, South San Francisco, CA, 94080, USA.
Gregory R SteinbergDivision of Endocrinology and Metabolism, Department of Medicine, McMaster University, 1280 Main St. W., Hamilton, Ontario, L8N 3Z5, Canada.
McMaster University · CAUniversity of Copenhagen · DKBoston Biomedical Research Institute · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USTakeda (United States) · USWayne State University · US

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
NIDDK NIH HHS P30 DK020572
6 · The paper itself

Abstract

objectiveFibroblast growth factor 21 (FGF21) shows great potential for the treatment of obesity and type 2 diabetes, as its long-acting analogue reduces body weight and improves lipid profiles of participants in clinical studies; however, the intracellular mechanisms mediating these effects are poorly understood. AMP-activated protein kinase (AMPK) is an important energy sensor of the cell and a molecular target for anti-diabetic medications. This work examined the role of AMPK in mediating the glucose and lipid-lowering effects of FGF21.

methodsInducible adipocyte AMPK β1β2 knockout mice (iβ1β2AKO) and littermate controls were fed a high fat diet (HFD) and treated with native FGF21 or saline for two weeks. Additionally, HFD-fed mice with knock-in mutations on the AMPK phosphorylation sites of acetyl-CoA carboxylase (ACC)1 and ACC2 (DKI mice) along with wild-type (WT) controls received long-acting FGF21 for two weeks.

resultsConsistent with previous studies, FGF21 treatment significantly reduced body weight, adiposity, and liver lipids in HFD fed mice. To add, FGF21 improved circulating lipids, glycemic control, and insulin sensitivity. These effects were independent of adipocyte AMPK and were not associated with changes in browning of white (WAT) and brown adipose tissue (BAT). Lastly, we assessed whether FGF21 exerted its effects through the AMPK/ACC axis, which is critical in the therapeutic benefits of the anti-diabetic medication metformin. ACC DKI mice had improved glucose and insulin tolerance and a reduction in body weight, body fat and hepatic steatosis similar to WT mice in response to FGF21 administration.

conclusionsThese data illustrate that the metabolic improvements upon FGF21 administration are independent of adipocyte AMPK, and do not require the inhibitory action of AMPK on ACC. This is in contrast to the anti-diabetic medication metformin and suggests that the treatment of obesity and diabetes with the combination of FGF21 and AMPK activators merits consideration.

Indexed as

Acetyl-CoA CarboxylaseAdipocytesAMP-Activated Protein Kinase KinasesAnimalsFibroblast Growth FactorsGlucoseHomeostasisLipid MetabolismLiverMaleMiceProtein KinasesAcetyl-CoA CarboxylaseAMP-Activated Protein Kinase Kinasesfibroblast growth factor 21Fibroblast Growth FactorsGlucoseProtein KinasesACCACC, acetyl-CoA carboxylaseACC DKI, ACC1-S79A and ACC2-S212A double knock-inAdipocyteAKT, protein kinase BAMPKAMPK, AMP-activated protein kinaseBAT, brown adipose tissueBrown fatCNS, central nervous systemCOX, cytochrome c oxidaseCreERT2, Cre recombinase – estrogen receptor T2DAG, diacylglycerolDiabetesFFA, free fatty acidFGF21FGF21, fibroblast growth factor 21FGFR1c, fibroblast growth factor receptor 1cGTT, glucose tolerance testgWAT, gonadal white adipose tissueH&E, hematoxylin and eosinHFD, high fat dietITT, insulin tolerance testiWAT, inguinal white adipose tissueiβ1β2AKO, inducible AMPK β1β2 adipocyte knockoutKLB, beta klothomTORC1, mammalian target of rapamycinNAFLD, non-alcoholic fatty liver diseaseObesityRER, respiratory exchange ratioTAG, triacylglycerolUCP1, uncoupling protein 1WAT, white adipose tissueWT, wildtype

Identifiers

PMID28580278
PMCPMC5444097
OpenAlexW2605119706

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.