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Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity

Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity
Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity

The epidemic of obesity imposes unprecedented challenges on human adipose tissue (WAT) storage capacity that may benefit from adaptive mechanisms to maintain adipocyte functionality. Here, we demonstrate that changes in the regulatory feedback set point control of Insig1/SREBP1 represent an adaptive response that preserves WAT lipid homeostasis in obese and insulin-resistant states. In our experiments, we show that Insig1 mRNA expression decreases in WAT from mice with obesity-associated insulin resistance and from morbidly obese humans and in in vitro models of adipocyte insulin resistance. Insig1 downregulation is part of an adaptive response that promotes the maintenance of SREBP1 maturation and facilitates lipogenesis and availability of appropriate levels of fatty acid unsaturation, partially compensating the antilipogenic effect associated with insulin resistance. We describe for the first time the existence of this adaptive mechanism in WAT, which involves Insig1/SREBP1 and preserves the degree of lipid unsaturation under conditions of obesity-induced insulin resistance. These adaptive mechanisms contribute to maintain lipid desaturation through preferential SCD1 regulation and facilitate fat storage in WAT, despite on-going metabolic stress.

3T3-L1 Cells, Adaptation, Physiological, Adipose Tissue, White, Animals, Down-Regulation, Humans, Insulin Resistance, Lipid Metabolism, Membrane Proteins, Mice, Mice, Knockout, Obesity, Obesity, Morbid, RNA, Messenger, Stearoyl-CoA Desaturase, Sterol Regulatory Element Binding Protein 1, Journal Article, Research Support, Non-U.S. Gov't
0012-1797
3697-3708
Carobbio, Stefania
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Hagen, Rachel M.
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Lelliott, Christopher J.
af26504c-561c-4afc-9e0e-26de86f3db8c
Slawik, Marc
2fa28a50-9447-4875-bdd7-4b2be433f0c7
Medina-Gomez, Gema
9e8167bb-cfac-4bec-8e25-da1b42120e26
Tan, Chong-Yew
7e1ea074-f229-4b76-a568-28cb5e63d289
Sicard, Audrey
003ccce1-690b-47b7-a2a6-5c3458ea84d3
Atherton, Helen J
bf8e3878-c8f2-487c-96c4-a6fc90ba95bb
Barbarroja, Nuria
ad10e864-08e0-4089-84e1-a6086a2f2a69
Bjursell, Mikael
e2ee6dc1-23de-44cf-998c-d942d4186134
Bohlooly-Y, Mohammad
299d7fac-3510-42fb-8c6e-da027e68b687
Virtue, Sam
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Tuthill, Antoinette
fc385d1a-b02c-4241-95a3-921ca9e3b53a
Lefai, Etienne
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Laville, Martine
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Wu, Tingting
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Considine, Robert V.
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Vidal, Hubert
d4a0e549-191c-4079-8633-9bfc99a7358d
Langin, Dominique
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Oresic, Matej
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Tinahones, Francisco J.
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Fernandez-Real, Jose Manuel
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Griffin, Julian L.
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Sethi, Jaswinder K.
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López, Miguel
114e013a-bed3-453a-ba45-1f967eafa36e
Vidal-Puig, Antonio
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Carobbio, Stefania
f8389d01-74c3-4d0d-aef0-0538c9ce13c4
Hagen, Rachel M.
b2a14bb3-74f4-43b4-9370-eba8dc4f16c3
Lelliott, Christopher J.
af26504c-561c-4afc-9e0e-26de86f3db8c
Slawik, Marc
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Medina-Gomez, Gema
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Tan, Chong-Yew
7e1ea074-f229-4b76-a568-28cb5e63d289
Sicard, Audrey
003ccce1-690b-47b7-a2a6-5c3458ea84d3
Atherton, Helen J
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Barbarroja, Nuria
ad10e864-08e0-4089-84e1-a6086a2f2a69
Bjursell, Mikael
e2ee6dc1-23de-44cf-998c-d942d4186134
Bohlooly-Y, Mohammad
299d7fac-3510-42fb-8c6e-da027e68b687
Virtue, Sam
5a5860ed-b7a9-4bee-a2cc-50a019b5bc5c
Tuthill, Antoinette
fc385d1a-b02c-4241-95a3-921ca9e3b53a
Lefai, Etienne
9c5eb14d-a7f8-45f9-9432-31367d0ea104
Laville, Martine
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Wu, Tingting
98f97f6b-5663-4f45-9959-2b14c4f9a5b7
Considine, Robert V.
308b79da-05cf-4816-8892-7364938c58b4
Vidal, Hubert
d4a0e549-191c-4079-8633-9bfc99a7358d
Langin, Dominique
f81195c3-c97e-4c15-b040-13f2afacae91
Oresic, Matej
2b178124-9f65-43ce-aa8b-33cc6166b53e
Tinahones, Francisco J.
a195a03e-3597-4a42-8e66-6975a800656b
Fernandez-Real, Jose Manuel
12118d97-ee7d-4423-85bf-55e72e365334
Griffin, Julian L.
efbf2925-ee1c-4e28-8e89-c1a70d143928
Sethi, Jaswinder K.
923f1a81-91e4-46cd-8853-bb4a979f5a85
López, Miguel
114e013a-bed3-453a-ba45-1f967eafa36e
Vidal-Puig, Antonio
7d46d380-1b9d-40cb-90a3-72679e143036

Carobbio, Stefania, Hagen, Rachel M., Lelliott, Christopher J., Slawik, Marc, Medina-Gomez, Gema, Tan, Chong-Yew, Sicard, Audrey, Atherton, Helen J, Barbarroja, Nuria, Bjursell, Mikael, Bohlooly-Y, Mohammad, Virtue, Sam, Tuthill, Antoinette, Lefai, Etienne, Laville, Martine, Wu, Tingting, Considine, Robert V., Vidal, Hubert, Langin, Dominique, Oresic, Matej, Tinahones, Francisco J., Fernandez-Real, Jose Manuel, Griffin, Julian L., Sethi, Jaswinder K., López, Miguel and Vidal-Puig, Antonio (2013) Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity. Diabetes, 62 (11), 3697-3708. (doi:10.2337/db12-1748).

Record type: Article

Abstract

The epidemic of obesity imposes unprecedented challenges on human adipose tissue (WAT) storage capacity that may benefit from adaptive mechanisms to maintain adipocyte functionality. Here, we demonstrate that changes in the regulatory feedback set point control of Insig1/SREBP1 represent an adaptive response that preserves WAT lipid homeostasis in obese and insulin-resistant states. In our experiments, we show that Insig1 mRNA expression decreases in WAT from mice with obesity-associated insulin resistance and from morbidly obese humans and in in vitro models of adipocyte insulin resistance. Insig1 downregulation is part of an adaptive response that promotes the maintenance of SREBP1 maturation and facilitates lipogenesis and availability of appropriate levels of fatty acid unsaturation, partially compensating the antilipogenic effect associated with insulin resistance. We describe for the first time the existence of this adaptive mechanism in WAT, which involves Insig1/SREBP1 and preserves the degree of lipid unsaturation under conditions of obesity-induced insulin resistance. These adaptive mechanisms contribute to maintain lipid desaturation through preferential SCD1 regulation and facilitate fat storage in WAT, despite on-going metabolic stress.

Full text not available from this repository.

More information

Accepted/In Press date: 1 August 2013
e-pub ahead of print date: 24 October 2013
Published date: November 2013
Keywords: 3T3-L1 Cells, Adaptation, Physiological, Adipose Tissue, White, Animals, Down-Regulation, Humans, Insulin Resistance, Lipid Metabolism, Membrane Proteins, Mice, Mice, Knockout, Obesity, Obesity, Morbid, RNA, Messenger, Stearoyl-CoA Desaturase, Sterol Regulatory Element Binding Protein 1, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 415247
URI: https://eprints.soton.ac.uk/id/eprint/415247
ISSN: 0012-1797
PURE UUID: c6de2ae6-77f9-4a77-9aed-a44e77005865
ORCID for Jaswinder K. Sethi: ORCID iD orcid.org/0000-0003-4157-0475

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Date deposited: 06 Nov 2017 17:30
Last modified: 14 Mar 2019 01:25

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Contributors

Author: Stefania Carobbio
Author: Rachel M. Hagen
Author: Christopher J. Lelliott
Author: Marc Slawik
Author: Gema Medina-Gomez
Author: Chong-Yew Tan
Author: Audrey Sicard
Author: Helen J Atherton
Author: Nuria Barbarroja
Author: Mikael Bjursell
Author: Mohammad Bohlooly-Y
Author: Sam Virtue
Author: Antoinette Tuthill
Author: Etienne Lefai
Author: Martine Laville
Author: Tingting Wu
Author: Robert V. Considine
Author: Hubert Vidal
Author: Dominique Langin
Author: Matej Oresic
Author: Francisco J. Tinahones
Author: Jose Manuel Fernandez-Real
Author: Julian L. Griffin
Author: Miguel López
Author: Antonio Vidal-Puig

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