Abcc5 Knockout Mice Have Lower Fat Mass and Increased Levels of Circulating GLP-1

Malgorzata Cyranka; Anna Veprik; Eleanor J. McKay; Nienke van Loon; Amber Thijsse; Luke Cotter; Nisha Hare; Affan Saibudeen; Swathi Lingam; Elisabete Pires; Pierre Larraufie; Frank Reimann; Fiona Gribble; Michelle Stewart; Elizabeth Bentley; Pamela Lear; James McCullagh; James Cantley; Roger D. Cox; Heidi de Wet

doi:10.1002/oby.22521

Abcc5 Knockout Mice Have Lower Fat Mass and Increased Levels of Circulating GLP-1

Malgorzata Cyranka, Anna Veprik, Eleanor J. McKay, Nienke van Loon, Amber Thijsse, Luke Cotter, Nisha Hare, Affan Saibudeen, Swathi Lingam, Elisabete Pires, Pierre Larraufie, Frank Reimann, Fiona Gribble, Michelle Stewart, Elizabeth Bentley, Pamela Lear, James McCullagh, James Cantley, Roger D. Cox, Heidi de Wet

Systems Medicine

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Abstract

Objective: A previous genome-wide association study linked overexpression of an ATP-binding cassette transporter, ABCC5, in humans with a susceptibility to developing type 2 diabetes with age. Specifically, ABCC5 gene overexpression was shown to be strongly associated with increased visceral fat mass and reduced peripheral insulin sensitivity. Currently, the role of ABCC5 in diabetes and obesity is unknown. This study reports the metabolic phenotyping of a global Abcc5 knockout mouse. Methods: A global Abcc5^-/- mouse was generated by CRISPR/Cas9. Fat mass was determined by weekly EchoMRI and fat pads were dissected and weighed at week 18. Glucose homeostasis was ascertained by an oral glucose tolerance test, intraperitoneal glucose tolerance test, and intraperitoneal insulin tolerance test. Energy expenditure and locomotor activity were measured using PhenoMaster cages. Glucagon-like peptide 1 (GLP-1) levels in plasma, primary gut cell cultures, and GLUTag cells were determined by enzyme-linked immunosorbent assay. Results: Abcc5^-/- mice had decreased fat mass and increased plasma levels of GLP-1, and they were more insulin sensitive and more active. Recombinant overexpression of ABCC5 protein in GLUTag cells decreased GLP-1 release. Conclusions: ABCC5 protein expression levels are inversely related to fat mass and appear to play a role in the regulation of GLP-1 secretion from enteroendocrine cells.

Original language	English
Pages (from-to)	1292-1304
Number of pages	13
Journal	Obesity
Volume	27
Issue number	8
DOIs	https://doi.org/10.1002/oby.22521
Publication status	Published - Aug 2019

ASJC Scopus subject areas

Medicine (miscellaneous)
Endocrinology, Diabetes and Metabolism
Endocrinology
Nutrition and Dietetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/oby.22521

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Cyranka, M., Veprik, A., McKay, E. J., van Loon, N., Thijsse, A., Cotter, L., Hare, N., Saibudeen, A., Lingam, S., Pires, E., Larraufie, P., Reimann, F., Gribble, F., Stewart, M., Bentley, E., Lear, P., McCullagh, J., Cantley, J., Cox, R. D., & de Wet, H. (2019). Abcc5 Knockout Mice Have Lower Fat Mass and Increased Levels of Circulating GLP-1. Obesity, 27(8), 1292-1304. https://doi.org/10.1002/oby.22521

@article{4b2a8da86fb543cba1e9f084846337b5,

title = "Abcc5 Knockout Mice Have Lower Fat Mass and Increased Levels of Circulating GLP-1",

abstract = "Objective: A previous genome-wide association study linked overexpression of an ATP-binding cassette transporter, ABCC5, in humans with a susceptibility to developing type 2 diabetes with age. Specifically, ABCC5 gene overexpression was shown to be strongly associated with increased visceral fat mass and reduced peripheral insulin sensitivity. Currently, the role of ABCC5 in diabetes and obesity is unknown. This study reports the metabolic phenotyping of a global Abcc5 knockout mouse. Methods: A global Abcc5-/- mouse was generated by CRISPR/Cas9. Fat mass was determined by weekly EchoMRI and fat pads were dissected and weighed at week 18. Glucose homeostasis was ascertained by an oral glucose tolerance test, intraperitoneal glucose tolerance test, and intraperitoneal insulin tolerance test. Energy expenditure and locomotor activity were measured using PhenoMaster cages. Glucagon-like peptide 1 (GLP-1) levels in plasma, primary gut cell cultures, and GLUTag cells were determined by enzyme-linked immunosorbent assay. Results: Abcc5-/- mice had decreased fat mass and increased plasma levels of GLP-1, and they were more insulin sensitive and more active. Recombinant overexpression of ABCC5 protein in GLUTag cells decreased GLP-1 release. Conclusions: ABCC5 protein expression levels are inversely related to fat mass and appear to play a role in the regulation of GLP-1 secretion from enteroendocrine cells.",

author = "Malgorzata Cyranka and Anna Veprik and McKay, {Eleanor J.} and {van Loon}, Nienke and Amber Thijsse and Luke Cotter and Nisha Hare and Affan Saibudeen and Swathi Lingam and Elisabete Pires and Pierre Larraufie and Frank Reimann and Fiona Gribble and Michelle Stewart and Elizabeth Bentley and Pamela Lear and James McCullagh and James Cantley and Cox, {Roger D.} and {de Wet}, Heidi",

year = "2019",

month = aug,

doi = "10.1002/oby.22521",

language = "English",

volume = "27",

pages = "1292--1304",

journal = "Obesity",

issn = "1930-7381",

publisher = "Wiley",

number = "8",

}

Cyranka, M, Veprik, A, McKay, EJ, van Loon, N, Thijsse, A, Cotter, L, Hare, N, Saibudeen, A, Lingam, S, Pires, E, Larraufie, P, Reimann, F, Gribble, F, Stewart, M, Bentley, E, Lear, P, McCullagh, J, Cantley, J, Cox, RD & de Wet, H 2019, 'Abcc5 Knockout Mice Have Lower Fat Mass and Increased Levels of Circulating GLP-1', Obesity, vol. 27, no. 8, pp. 1292-1304. https://doi.org/10.1002/oby.22521

TY - JOUR

T1 - Abcc5 Knockout Mice Have Lower Fat Mass and Increased Levels of Circulating GLP-1

AU - Cyranka, Malgorzata

AU - Veprik, Anna

AU - McKay, Eleanor J.

AU - van Loon, Nienke

AU - Thijsse, Amber

AU - Cotter, Luke

AU - Hare, Nisha

AU - Saibudeen, Affan

AU - Lingam, Swathi

AU - Pires, Elisabete

AU - Larraufie, Pierre

AU - Reimann, Frank

AU - Gribble, Fiona

AU - Stewart, Michelle

AU - Bentley, Elizabeth

AU - Lear, Pamela

AU - McCullagh, James

AU - Cantley, James

AU - Cox, Roger D.

AU - de Wet, Heidi

PY - 2019/8

Y1 - 2019/8

N2 - Objective: A previous genome-wide association study linked overexpression of an ATP-binding cassette transporter, ABCC5, in humans with a susceptibility to developing type 2 diabetes with age. Specifically, ABCC5 gene overexpression was shown to be strongly associated with increased visceral fat mass and reduced peripheral insulin sensitivity. Currently, the role of ABCC5 in diabetes and obesity is unknown. This study reports the metabolic phenotyping of a global Abcc5 knockout mouse. Methods: A global Abcc5-/- mouse was generated by CRISPR/Cas9. Fat mass was determined by weekly EchoMRI and fat pads were dissected and weighed at week 18. Glucose homeostasis was ascertained by an oral glucose tolerance test, intraperitoneal glucose tolerance test, and intraperitoneal insulin tolerance test. Energy expenditure and locomotor activity were measured using PhenoMaster cages. Glucagon-like peptide 1 (GLP-1) levels in plasma, primary gut cell cultures, and GLUTag cells were determined by enzyme-linked immunosorbent assay. Results: Abcc5-/- mice had decreased fat mass and increased plasma levels of GLP-1, and they were more insulin sensitive and more active. Recombinant overexpression of ABCC5 protein in GLUTag cells decreased GLP-1 release. Conclusions: ABCC5 protein expression levels are inversely related to fat mass and appear to play a role in the regulation of GLP-1 secretion from enteroendocrine cells.

AB - Objective: A previous genome-wide association study linked overexpression of an ATP-binding cassette transporter, ABCC5, in humans with a susceptibility to developing type 2 diabetes with age. Specifically, ABCC5 gene overexpression was shown to be strongly associated with increased visceral fat mass and reduced peripheral insulin sensitivity. Currently, the role of ABCC5 in diabetes and obesity is unknown. This study reports the metabolic phenotyping of a global Abcc5 knockout mouse. Methods: A global Abcc5-/- mouse was generated by CRISPR/Cas9. Fat mass was determined by weekly EchoMRI and fat pads were dissected and weighed at week 18. Glucose homeostasis was ascertained by an oral glucose tolerance test, intraperitoneal glucose tolerance test, and intraperitoneal insulin tolerance test. Energy expenditure and locomotor activity were measured using PhenoMaster cages. Glucagon-like peptide 1 (GLP-1) levels in plasma, primary gut cell cultures, and GLUTag cells were determined by enzyme-linked immunosorbent assay. Results: Abcc5-/- mice had decreased fat mass and increased plasma levels of GLP-1, and they were more insulin sensitive and more active. Recombinant overexpression of ABCC5 protein in GLUTag cells decreased GLP-1 release. Conclusions: ABCC5 protein expression levels are inversely related to fat mass and appear to play a role in the regulation of GLP-1 secretion from enteroendocrine cells.

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U2 - 10.1002/oby.22521

DO - 10.1002/oby.22521

M3 - Article

C2 - 31338999

AN - SCOPUS:85069775184

SN - 1930-7381

VL - 27

SP - 1292

EP - 1304

JO - Obesity

JF - Obesity

IS - 8

ER -

Abcc5 Knockout Mice Have Lower Fat Mass and Increased Levels of Circulating GLP-1

Abstract

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