Evidence map›Paper›PMID 36916878›Full record

ArticleThe Journal of clinical endocrinology and metabolism2023

Impaired Adipocyte SLC7A10 Promotes Lipid Storage in Association With Insulin Resistance and Altered BCAA Metabolism.

Regine Å Jersin, Divya Sri Priyanka Tallapragada, Linn Skartveit, Mona S Bjune, Maheswary Muniandy, Sindre Lee-Ødegård, Sini Heinonen, Marcus Alvarez, Kåre Inge Birkeland, Christian André Drevon and 6 more

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

Article in The Journal of clinical endocrinology and metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. The emerging role of branched-chain amino acid metabolism in obesity.International journal of obesity (2005) · 2026
    Review
  2. Lifestyles, metabolome and diabetic kidney disease: a cohort study.QJM : monthly journal of the Association of Physicians · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Human abdominal subcutaneous-derived active beige adipocytes carryingFrontiers in cell and developmental biology · 2023
    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

16 authors at 6 institutions in 3 countries.

Regine Å JersinMohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway.ORCID 0000-0002-4192-4547
Divya Sri Priyanka TallapragadaMohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway.
Linn SkartveitMohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway.
Mona S BjuneMohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway.
Maheswary MuniandyObesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland.
Sindre Lee-ØdegårdDepartment of Transplantation Medicine, The University of Oslo, Institute of Clinical Medicine, and Oslo University Hospital, N-0372 Oslo, Norway.
Sini HeinonenObesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland.
Marcus AlvarezDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Kåre Inge BirkelandDepartment of Transplantation Medicine, The University of Oslo, Institute of Clinical Medicine, and Oslo University Hospital, N-0372 Oslo, Norway.
Christian André DrevonDepartment of Nutrition, The University of Oslo, Institute of Basic Medical Sciences, N-0372 Oslo, Norway.
Päivi PajukantaDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Adrian McCannBevital A/S, Laboratoriebygget, Haukeland University Hospital, N-5021 Bergen, Norway.
Kirsi H PietiläinenObesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland.
Melina ClaussnitzerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Gunnar MellgrenMohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway.
Simon N DankelMohn Nutrition Research Laboratory, Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway.ORCID 0000-0001-6972-1824
Haukeland University Hospital · NOUniversity of Helsinki · FIOslo University Hospital · NOUniversity of California, Los Angeles · USBroad Institute · USUniversity of Oslo · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

contextThe neutral amino acid transporter SLC7A10/ASC-1 is an adipocyte-expressed gene with reduced expression in insulin resistance and obesity. Inhibition of SLC7A10 in adipocytes was shown to increase lipid accumulation despite decreasing insulin-stimulated uptake of glucose, a key substrate for de novo lipogenesis. These data imply that alternative lipogenic substrates to glucose fuel continued lipid accumulation during insulin resistance in obesity.

objectiveWe examined whether increased lipid accumulation during insulin resistance in adipocytes may involve alter flux of lipogenic amino acids dependent on SLC7A10 expression and activity, and whether this is reflected by extracellular and circulating concentrations of marker metabolites.

methodsIn adipocyte cultures with impaired SLC7A10, we performed RNA sequencing and relevant functional assays. By targeted metabolite analyses (GC-MS/MS), flux of all amino acids and selected metabolites were measured in human and mouse adipose cultures. Additionally, SLC7A10 mRNA levels in human subcutaneous adipose tissue (SAT) were correlated to candidate metabolites and adiposity phenotypes in 2 independent cohorts.

resultsSLC7A10 impairment altered expression of genes related to metabolic processes, including branched-chain amino acid (BCAA) catabolism, lipogenesis, and glyceroneogenesis. In 3T3-L1 adipocytes, SLC7A10 inhibition increased fatty acid uptake and cellular content of glycerol and cholesterol. SLC7A10 impairment in SAT cultures altered uptake of aspartate and glutamate, and increased net uptake of BCAAs, while increasing the net release of the valine catabolite 3- hydroxyisobutyrate (3-HIB). In human cohorts, SLC7A10 mRNA correlated inversely with total fat mass, circulating triacylglycerols, BCAAs, and 3-HIB.

conclusionReduced SLC7A10 activity strongly affects flux of BCAAs in adipocytes, which may fuel continued lipogenesis during insulin resistance, and be reflected in increased circulating levels of the valine-derived catabolite 3-HIB.

Indexed as

Insulin ResistanceAdipocytesAmino AcidsAmino Acids, Branched-ChainAmino Acid Transport System y+AnimalsFatty AcidsGlucoseHumansLipid MetabolismMiceObesityRNA, MessengerTandem Mass SpectrometryValineAmino AcidsAmino Acids, Branched-ChainAmino Acid Transport System y+Fatty AcidsGlucoseRNA, MessengerSLC7A10 protein, humanSlc7a10 protein, mouseValineadipocytesamino acid metabolismbranched-chain amino acidsinsulin resistancelipid storageobesity

Identifiers

PMID36916878
PMCPMC10438883
OpenAlexW4324129682

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.