Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes

D Ferland-McCollough; D S Fernandez-Twinn; I G Cannell; H David; M Warner; A A Vaag; Jette Bork-Jensen; C Brøns; T W Gant; A E Willis; K Siddle; M Bushell; S E Ozanne

doi:10.1038/cdd.2011.183

Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes

D Ferland-McCollough, D S Fernandez-Twinn, I G Cannell, H David, M Warner, A A Vaag, Jette Bork-Jensen, C Brøns, T W Gant, A E Willis, K Siddle, M Bushell, S E Ozanne

94 Citationer (Scopus)

Abstract

Nutrition during early mammalian development permanently influences health of the adult, including increasing the risk of type 2 diabetes and coronary heart disease. However, the molecular mechanisms underlying such programming are poorly defined. Here we demonstrate that programmed changes in miRNA expression link early-life nutrition to long-term health. Specifically, we show that miR-483-3p is upregulated in adipose tissue from low-birth-weight adult humans and prediabetic adult rats exposed to suboptimal nutrition in early life. We demonstrate that manipulation of miR-483-3p levels in vitro substantially modulates the capacity of adipocytes to differentiate and store lipids. We show that some of these effects are mediated by translational repression of growth/differentiation factor-3, a target of miR-483-3p. We propose that increased miR-483-3p expression in vivo, programmed by early-life nutrition, limits storage of lipids in adipose tissue, causing lipotoxicity and insulin resistance and thus increasing susceptibility to metabolic disease.

Originalsprog	Engelsk
Tidsskrift	Cell Death and Differentiation
Vol/bind	19
Sider (fra-til)	1003-12
Antal sider	10
ISSN	1350-9047
DOI	https://doi.org/10.1038/cdd.2011.183
Status	Udgivet - jun. 2012

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Ferland-McCollough, D., Fernandez-Twinn, D. S., Cannell, I. G., David, H., Warner, M., Vaag, A. A., Bork-Jensen, J., Brøns, C., Gant, T. W., Willis, A. E., Siddle, K., Bushell, M., & Ozanne, S. E. (2012). Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes. Cell Death and Differentiation, 19, 1003-12. https://doi.org/10.1038/cdd.2011.183

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title = "Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes",

abstract = "Nutrition during early mammalian development permanently influences health of the adult, including increasing the risk of type 2 diabetes and coronary heart disease. However, the molecular mechanisms underlying such programming are poorly defined. Here we demonstrate that programmed changes in miRNA expression link early-life nutrition to long-term health. Specifically, we show that miR-483-3p is upregulated in adipose tissue from low-birth-weight adult humans and prediabetic adult rats exposed to suboptimal nutrition in early life. We demonstrate that manipulation of miR-483-3p levels in vitro substantially modulates the capacity of adipocytes to differentiate and store lipids. We show that some of these effects are mediated by translational repression of growth/differentiation factor-3, a target of miR-483-3p. We propose that increased miR-483-3p expression in vivo, programmed by early-life nutrition, limits storage of lipids in adipose tissue, causing lipotoxicity and insulin resistance and thus increasing susceptibility to metabolic disease.",

keywords = "3' Untranslated Regions, Adipose Tissue, Adult, Animals, Animals, Newborn, Base Sequence, Cell Differentiation, Diabetes Mellitus, Type 2, Diet, Disease Models, Animal, Down-Regulation, Female, Growth Differentiation Factor 3, HEK293 Cells, Humans, Lipid Metabolism, Male, MicroRNAs, RNA Interference, RNA, Small Interfering, Rats, Rats, Wistar",

author = "D Ferland-McCollough and Fernandez-Twinn, {D S} and Cannell, {I G} and H David and M Warner and Vaag, {A A} and Jette Bork-Jensen and C Br{\o}ns and Gant, {T W} and Willis, {A E} and K Siddle and M Bushell and Ozanne, {S E}",

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doi = "10.1038/cdd.2011.183",

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T1 - Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes

AU - Ferland-McCollough, D

AU - Fernandez-Twinn, D S

AU - Cannell, I G

AU - David, H

AU - Warner, M

AU - Vaag, A A

AU - Bork-Jensen, Jette

AU - Brøns, C

AU - Gant, T W

AU - Willis, A E

AU - Siddle, K

AU - Bushell, M

AU - Ozanne, S E

PY - 2012/6

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N2 - Nutrition during early mammalian development permanently influences health of the adult, including increasing the risk of type 2 diabetes and coronary heart disease. However, the molecular mechanisms underlying such programming are poorly defined. Here we demonstrate that programmed changes in miRNA expression link early-life nutrition to long-term health. Specifically, we show that miR-483-3p is upregulated in adipose tissue from low-birth-weight adult humans and prediabetic adult rats exposed to suboptimal nutrition in early life. We demonstrate that manipulation of miR-483-3p levels in vitro substantially modulates the capacity of adipocytes to differentiate and store lipids. We show that some of these effects are mediated by translational repression of growth/differentiation factor-3, a target of miR-483-3p. We propose that increased miR-483-3p expression in vivo, programmed by early-life nutrition, limits storage of lipids in adipose tissue, causing lipotoxicity and insulin resistance and thus increasing susceptibility to metabolic disease.

AB - Nutrition during early mammalian development permanently influences health of the adult, including increasing the risk of type 2 diabetes and coronary heart disease. However, the molecular mechanisms underlying such programming are poorly defined. Here we demonstrate that programmed changes in miRNA expression link early-life nutrition to long-term health. Specifically, we show that miR-483-3p is upregulated in adipose tissue from low-birth-weight adult humans and prediabetic adult rats exposed to suboptimal nutrition in early life. We demonstrate that manipulation of miR-483-3p levels in vitro substantially modulates the capacity of adipocytes to differentiate and store lipids. We show that some of these effects are mediated by translational repression of growth/differentiation factor-3, a target of miR-483-3p. We propose that increased miR-483-3p expression in vivo, programmed by early-life nutrition, limits storage of lipids in adipose tissue, causing lipotoxicity and insulin resistance and thus increasing susceptibility to metabolic disease.

KW - 3' Untranslated Regions

KW - Adipose Tissue

KW - Adult

KW - Animals

KW - Animals, Newborn

KW - Base Sequence

KW - Cell Differentiation

KW - Diabetes Mellitus, Type 2

KW - Diet

KW - Disease Models, Animal

KW - Down-Regulation

KW - Female

KW - Growth Differentiation Factor 3

KW - HEK293 Cells

KW - Humans

KW - Lipid Metabolism

KW - Male

KW - MicroRNAs

KW - RNA Interference

KW - RNA, Small Interfering

KW - Rats

KW - Rats, Wistar

U2 - 10.1038/cdd.2011.183

DO - 10.1038/cdd.2011.183

M3 - Journal article

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SN - 1350-9047

VL - 19

SP - 1003

EP - 1012

JO - Cell Differentiation and Development

JF - Cell Differentiation and Development

ER -

Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes

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