Evidence map›Paper›PMID 26977393›Full record

ArticleMolecular metabolism2016

Acyl CoA synthetase 5 (ACSL5) ablation in mice increases energy expenditure and insulin sensitivity and delays fat absorption.

Thomas A Bowman, Kayleigh R O'Keeffe, Theresa D'Aquila, Qing Wu Yan, John D Griffin, Elizabeth A Killion, Deanna M Salter, Douglas G Mashek, Kimberly K Buhman, Andrew S Greenberg

Open access · goldAbstract read
In one paragraph

Article in Molecular metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
7.2field-weighted citation impact, top 3% 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

54 citing papers in PubMed, 101 citations in OpenAlex.

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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

10 authors at 4 institutions in 1 country.

Thomas A BowmanJean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. Electronic address: thomas.bowman@tufts.edu.
Kayleigh R O'KeeffeJean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. Electronic address: kokeeffe@live.unc.edu.
Theresa D'AquilaDepartment of Nutrition Science, Purdue University, West Lafayette, IN, USA. Electronic address: tdaquila@gmail.com.
Qing Wu YanJean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. Electronic address: qing-wu.yan@tufts.edu.
John D GriffinJean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. Electronic address: john.griffin@tufts.edu.
Elizabeth A KillionJean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. Electronic address: elizabeth.killion@tufts.edu.
Deanna M SalterJean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. Electronic address: deanna.salter@tufts.edu.
Douglas G MashekDepartment of Food Science and Nutrition, University of Minnesota, St. Paul, MN, USA. Electronic address: dmashek@umn.edu.
Kimberly K BuhmanDepartment of Nutrition Science, Purdue University, West Lafayette, IN, USA. Electronic address: kbuhman@purdue.edu.
Andrew S GreenbergJean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. Electronic address: andrew.greenberg@tufts.edu.
Jean Mayer Human Nutrition Research Center on Aging · USTufts University · USPurdue University West Lafayette · USUniversity of Minnesota · US

Funding

Transgenic CoreP30DK046200 · NIDDK · TUFTS MEDICAL CENTER · PI HU, FRANK B · 1992 to 2021
$25.0M
Indiana Clinical and Translational Sciences InstituteUL1TR001108 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$23.3M
Obesity and Energy Metabolism CoreP30DK050456 · NIDDK · UNIVERSITY OF MINNESOTA TWIN CITIES · PI JENSEN, MICHAEL D. · 1995 to 2015
$17.0M
Research Training Program in Nutrition, Obesity and Metabolic DisordersT32DK062032 · NIDDK · TUFTS UNIVERSITY BOSTON · PI GREENBERG, ANDREW S · 2002 to 2016
$2.6M
Role of ACSL5 in Intestinal and Liver Triacylglycerol MetabolismR01DK098606 · NIDDK · TUFTS UNIVERSITY BOSTON · PI GREENBERG, ANDREW S · 2014 to 2016
$1.0M
Age Dependent Role of Bisphenol A in Obesity and Insulin ResistanceU01ES020958 · NIEHS · TUFTS UNIVERSITY BOSTON · PI GREENBERG, ANDREW S · 2011 to 2014
$313k
Role of Perilipin in Hepatic Steatosis and MetabolismF32DK095538 · NIDDK · TUFTS UNIVERSITY BOSTON · PI BOWMAN, THOMAS A. · 2012 to 2014
$187k
NCATS NIH HHS UL1 TR001108NIDDK NIH HHS F32 DK095538NIDDK NIH HHS P30 DK046200NIDDK NIH HHS P30 DK050456NIDDK NIH HHS R01 DK098606NIDDK NIH HHS T32 DK062032NIEHS NIH HHS U01 ES020958
6 · The paper itself

Abstract

objectiveThe family of acyl-CoA synthetase enzymes (ACSL) activates fatty acids within cells to generate long chain fatty acyl CoA (FACoA). The differing metabolic fates of FACoAs such as incorporation into neutral lipids, phospholipids, and oxidation pathways are differentially regulated by the ACSL isoforms. In vitro studies have suggested a role for ACSL5 in triglyceride synthesis; however, we have limited understanding of the in vivo actions of this ACSL isoform.

methodsTo elucidate the in vivo actions of ACSL5 we generated a line of mice in which ACSL5 expression was ablated in all tissues (ACSL5 (-/-) ).

resultsAblation of ACSL5 reduced ACSL activity by ∼80% in jejunal mucosa, ∼50% in liver, and ∼37% in brown adipose tissue lysates. Body composition studies revealed that ACSL5 (-/-) , as compared to control ACSL5 (loxP/loxP) , mice had significantly reduced fat mass and adipose fat pad weights. Indirect calorimetry studies demonstrated that ACSL5 (-/-) had increased metabolic rates, and in the dark phase, increased respiratory quotient. In ACSL5 (-/-) mice, fasting glucose and serum triglyceride were reduced; and insulin sensitivity was improved during an insulin tolerance test. Both hepatic mRNA (∼16-fold) and serum levels of fibroblast growth factor 21 (FGF21) (∼13-fold) were increased in ACSL5 (-/-) as compared to ACSL5 (loxP/loxP) . Consistent with increased FGF21 serum levels, uncoupling protein-1 gene (Ucp1) and PPAR-gamma coactivator 1-alpha gene (Pgc1α) transcript levels were increased in gonadal adipose tissue. To further evaluate ACSL5 function in intestine, mice were gavaged with an olive oil bolus; and the rate of triglyceride appearance in serum was found to be delayed in ACSL5 (-/-) mice as compared to control mice.

conclusionsIn summary, ACSL5 (-/-) mice have increased hepatic and serum FGF21 levels, reduced adiposity, improved insulin sensitivity, increased energy expenditure and delayed triglyceride absorption. These studies suggest that ACSL5 is an important regulator of whole-body energy metabolism and ablation of ACSL5 may antagonize the development of obesity and insulin resistance.

Indexed as

ACSLACSL5−/−, mice with global ablation of ACSL5ACSL, long-chain acyl-CoA synthetaseAcyl-CoAAUC, area under the curveDietary fat absorptionES, embryonic stemFGF21FGF21, fibroblast growth factor 21IntestineITT, insulin tolerance testLiverNAFLD, non-alcoholic fatty liver diseasePGC1α, PPAR-gamma coactivator 1αPPAR, peroxisome proliferator activated receptorRER, respiratory exchange ratioSDS, sodium dodecyl sulfateSREBP1c, steroid response element binding protein-1cT2DM, type2 diabetesUCP1, uncoupling protein-1VLDL, very low density lipoprotein

Identifiers

PMID26977393
PMCPMC4770262
OpenAlexW2238444019

What Socratic 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 Socratic graph.