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 Citations (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.

Original language	English
Journal	Cell Death and Differentiation
Volume	19
Pages (from-to)	1003-12
Number of pages	10
ISSN	1350-9047
DOIs	https://doi.org/10.1038/cdd.2011.183
Publication status	Published - Jun 2012

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

UN SDGs

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

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10.1038/cdd.2011.183

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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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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.",

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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

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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

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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

Abstract

Keywords

UN SDGs

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