Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance

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Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance. / Jersin, Regine Å.; Tallapragada, Divya Sri Priyanka; Madsen, André; Skartveit, Linn; Fjære, Even; McCann, Adrian; Dyer, Laurence; Willems, Aron; Bjune, Jan-Inge; Bjune, Mona S.; Våge, Villy; Nielsen, Hans Jørgen; Thorsen, Håvard Luong; Nedrebø, Bjørn Gunnar; Busch, Christian; Steen, Vidar M.; Blüher, Matthias; Jacobson, Peter; Svensson, Per-Arne; Fernø, Johan; Rydén, Mikael; Arner, Peter; Nygård, Ottar; Claussnitzer, Melina; Ellingsen, Ståle; Madsen, Lise; Sagen, Jørn V.; Mellgren, Gunnar; Dankel, Simon N.

In: Diabetes, Vol. 70, No. 3, 2021, p. 680-695.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Jersin, RÅ, Tallapragada, DSP, Madsen, A, Skartveit, L, Fjære, E, McCann, A, Dyer, L, Willems, A, Bjune, J-I, Bjune, MS, Våge, V, Nielsen, HJ, Thorsen, HL, Nedrebø, BG, Busch, C, Steen, VM, Blüher, M, Jacobson, P, Svensson, P-A, Fernø, J, Rydén, M, Arner, P, Nygård, O, Claussnitzer, M, Ellingsen, S, Madsen, L, Sagen, JV, Mellgren, G & Dankel, SN 2021, 'Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance', Diabetes, vol. 70, no. 3, pp. 680-695. https://doi.org/10.2337/db20-0096

APA

Jersin, R. Å., Tallapragada, D. S. P., Madsen, A., Skartveit, L., Fjære, E., McCann, A., Dyer, L., Willems, A., Bjune, J-I., Bjune, M. S., Våge, V., Nielsen, H. J., Thorsen, H. L., Nedrebø, B. G., Busch, C., Steen, V. M., Blüher, M., Jacobson, P., Svensson, P-A., ... Dankel, S. N. (2021). Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance. Diabetes, 70(3), 680-695. https://doi.org/10.2337/db20-0096

Vancouver

Jersin RÅ, Tallapragada DSP, Madsen A, Skartveit L, Fjære E, McCann A et al. Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance. Diabetes. 2021;70(3):680-695. https://doi.org/10.2337/db20-0096

Author

Jersin, Regine Å. ; Tallapragada, Divya Sri Priyanka ; Madsen, André ; Skartveit, Linn ; Fjære, Even ; McCann, Adrian ; Dyer, Laurence ; Willems, Aron ; Bjune, Jan-Inge ; Bjune, Mona S. ; Våge, Villy ; Nielsen, Hans Jørgen ; Thorsen, Håvard Luong ; Nedrebø, Bjørn Gunnar ; Busch, Christian ; Steen, Vidar M. ; Blüher, Matthias ; Jacobson, Peter ; Svensson, Per-Arne ; Fernø, Johan ; Rydén, Mikael ; Arner, Peter ; Nygård, Ottar ; Claussnitzer, Melina ; Ellingsen, Ståle ; Madsen, Lise ; Sagen, Jørn V. ; Mellgren, Gunnar ; Dankel, Simon N. / Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance. In: Diabetes. 2021 ; Vol. 70, No. 3. pp. 680-695.

Bibtex

@article{cb18ec1debb54984adffbc6960fe9290,
title = "Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance",
abstract = "Elucidation of mechanisms that govern lipid storage, oxidative stress, and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter-1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance, and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of SCD (lipid storage) and downregulation of CPT1A (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance, and type 2 diabetes.",
author = "Jersin, {Regine {\AA}.} and Tallapragada, {Divya Sri Priyanka} and Andr{\'e} Madsen and Linn Skartveit and Even Fj{\ae}re and Adrian McCann and Laurence Dyer and Aron Willems and Jan-Inge Bjune and Bjune, {Mona S.} and Villy V{\aa}ge and Nielsen, {Hans J{\o}rgen} and Thorsen, {H{\aa}vard Luong} and Nedreb{\o}, {Bj{\o}rn Gunnar} and Christian Busch and Steen, {Vidar M.} and Matthias Bl{\"u}her and Peter Jacobson and Per-Arne Svensson and Johan Fern{\o} and Mikael Ryd{\'e}n and Peter Arner and Ottar Nyg{\aa}rd and Melina Claussnitzer and St{\aa}le Ellingsen and Lise Madsen and Sagen, {J{\o}rn V.} and Gunnar Mellgren and Dankel, {Simon N.}",
year = "2021",
doi = "10.2337/db20-0096",
language = "English",
volume = "70",
pages = "680--695",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "3",

}

RIS

TY - JOUR

T1 - Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance

AU - Jersin, Regine Å.

AU - Tallapragada, Divya Sri Priyanka

AU - Madsen, André

AU - Skartveit, Linn

AU - Fjære, Even

AU - McCann, Adrian

AU - Dyer, Laurence

AU - Willems, Aron

AU - Bjune, Jan-Inge

AU - Bjune, Mona S.

AU - Våge, Villy

AU - Nielsen, Hans Jørgen

AU - Thorsen, Håvard Luong

AU - Nedrebø, Bjørn Gunnar

AU - Busch, Christian

AU - Steen, Vidar M.

AU - Blüher, Matthias

AU - Jacobson, Peter

AU - Svensson, Per-Arne

AU - Fernø, Johan

AU - Rydén, Mikael

AU - Arner, Peter

AU - Nygård, Ottar

AU - Claussnitzer, Melina

AU - Ellingsen, Ståle

AU - Madsen, Lise

AU - Sagen, Jørn V.

AU - Mellgren, Gunnar

AU - Dankel, Simon N.

PY - 2021

Y1 - 2021

N2 - Elucidation of mechanisms that govern lipid storage, oxidative stress, and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter-1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance, and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of SCD (lipid storage) and downregulation of CPT1A (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance, and type 2 diabetes.

AB - Elucidation of mechanisms that govern lipid storage, oxidative stress, and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter-1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance, and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of SCD (lipid storage) and downregulation of CPT1A (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance, and type 2 diabetes.

U2 - 10.2337/db20-0096

DO - 10.2337/db20-0096

M3 - Journal article

C2 - 33408126

AN - SCOPUS:85102217709

VL - 70

SP - 680

EP - 695

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 3

ER -

ID: 260747765