Fenretinide prevents obesity in aged female mice in association with increased retinoid and estrogen-signaling

Kirsty D Shearer; Nicola Morrice; Claire  Henderson; Jenny  Reekie; George McIlroy; Peter J McCaffery; Mirela Delibegovic; Nimesh Mody

doi:10.1002/oby.21164

Fenretinide prevents obesity in aged female mice in association with increased retinoid and estrogen-signaling

Kirsty D Shearer, Nicola Morrice, Claire Henderson, Jenny Reekie, George McIlroy, Peter J McCaffery, Mirela Delibegovic, Nimesh Mody^* (Corresponding Author)

^*Corresponding author for this work

University of Aberdeen

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

Objective
The synthetic retinoid Fenretinide (FEN) inhibits adiposity in male mice fed a high-fat-diet (HFD) in association with alterations in retinoic acid (RA)-signaling. Young female mice are protected from obesity via estrogen-signaling. We therefore investigated whether FEN also influences adiposity in aged female mice differing in parity, and whether such effects are mediated by retinoid and estrogen-signaling.
Design and Methods
Aged nulliparous and parous female mice were maintained on HFD±FEN and adiposity was assessed. Quantitative-PCR was performed on white adipose tissue (WAT), liver and 3T3-L1 adipocytes treated with RA or FEN±estrogen.
Results
Parous females were more obese than nulliparous mice independent of age. FEN-HFD prevented the HFD-induced increase in adiposity and leptin levels independently of parity. FEN-HFD induced retinoid-responsive genes in WAT and liver. Parous females had reduced expression of hepatic estrogen-responsive genes but FEN-HFD up-regulated WAT Cyp19a1 and Esr2 in parous mice. Estrogen and RA acted synergistically to increase RA-receptor (RAR)-mediated gene expression in 3T3-L1 adipocytes. FEN increased Cyp19a1 and Esr2, similar to our findings in vivo.
Conclusions
The prevention of adiposity by FEN in response to HFD in female mice appears to involve increased retinoid-signaling in association with induction of local estrogen production and estrogen-signaling in WAT.

Original language	English
Pages (from-to)	1655-1662
Number of pages	8
Journal	Obesity
Volume	23
Issue number	8
Early online date	14 Jul 2015
DOIs	https://doi.org/10.1002/oby.21164
Publication status	Published - Aug 2015

Bibliographical note

Acknowledgments
The authors thank J.R. Speakman (UoA) for invaluable discussion regarding energy expenditure, T. Martin (Johnson & Johnson, NJ) and U. Thurneer (Cilag AG, Switzerland) for fenretinide, to use completely without restriction or obligation, and undergraduate student K. Towle (UoA) for assisting in experiments.

Funded by
British Heart Foundation Intermediate Basic Research Fellowship. Grant Number: FS/09/026
Research Councils UK Fellowship
European Foundation for the Study of Diabetes (EFSD)/Lilly
Biotechnology and Biological Sciences Research Council (BBSRC) studentship
University of Aberdeen (UoA) Centre for Genome-Enabled Biology & Medicine (CGEBM) studentship
BBSRC. Grant Number: BB/G014272/1

Keywords

Female Mice
Aged
Fenretinide
Obesity
Retinoid
Estrogen

UN SDGs

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

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Cite this

@article{0530e0899e2b4d75b15ce2cad289850c,

title = "Fenretinide prevents obesity in aged female mice in association with increased retinoid and estrogen-signaling",

abstract = "ObjectiveThe synthetic retinoid Fenretinide (FEN) inhibits adiposity in male mice fed a high-fat-diet (HFD) in association with alterations in retinoic acid (RA)-signaling. Young female mice are protected from obesity via estrogen-signaling. We therefore investigated whether FEN also influences adiposity in aged female mice differing in parity, and whether such effects are mediated by retinoid and estrogen-signaling. Design and MethodsAged nulliparous and parous female mice were maintained on HFD±FEN and adiposity was assessed. Quantitative-PCR was performed on white adipose tissue (WAT), liver and 3T3-L1 adipocytes treated with RA or FEN±estrogen.ResultsParous females were more obese than nulliparous mice independent of age. FEN-HFD prevented the HFD-induced increase in adiposity and leptin levels independently of parity. FEN-HFD induced retinoid-responsive genes in WAT and liver. Parous females had reduced expression of hepatic estrogen-responsive genes but FEN-HFD up-regulated WAT Cyp19a1 and Esr2 in parous mice. Estrogen and RA acted synergistically to increase RA-receptor (RAR)-mediated gene expression in 3T3-L1 adipocytes. FEN increased Cyp19a1 and Esr2, similar to our findings in vivo. ConclusionsThe prevention of adiposity by FEN in response to HFD in female mice appears to involve increased retinoid-signaling in association with induction of local estrogen production and estrogen-signaling in WAT.",

keywords = "Female Mice, Aged, Fenretinide, Obesity, Retinoid, Estrogen",

author = "Shearer, {Kirsty D} and Nicola Morrice and Claire Henderson and Jenny Reekie and George McIlroy and McCaffery, {Peter J} and Mirela Delibegovic and Nimesh Mody",

note = "Acknowledgments The authors thank J.R. Speakman (UoA) for invaluable discussion regarding energy expenditure, T. Martin (Johnson & Johnson, NJ) and U. Thurneer (Cilag AG, Switzerland) for fenretinide, to use completely without restriction or obligation, and undergraduate student K. Towle (UoA) for assisting in experiments. Funded by British Heart Foundation Intermediate Basic Research Fellowship. Grant Number: FS/09/026 Research Councils UK Fellowship European Foundation for the Study of Diabetes (EFSD)/Lilly Biotechnology and Biological Sciences Research Council (BBSRC) studentship University of Aberdeen (UoA) Centre for Genome-Enabled Biology & Medicine (CGEBM) studentship BBSRC. Grant Number: BB/G014272/1",

year = "2015",

month = aug,

doi = "10.1002/oby.21164",

language = "English",

volume = "23",

pages = "1655--1662",

journal = "Obesity",

issn = "1930-7381",

publisher = "Wiley-Blackwell",

number = "8",

}

TY - JOUR

T1 - Fenretinide prevents obesity in aged female mice in association with increased retinoid and estrogen-signaling

AU - Shearer, Kirsty D

AU - Morrice, Nicola

AU - Henderson, Claire

AU - Reekie, Jenny

AU - McIlroy, George

AU - McCaffery, Peter J

AU - Delibegovic, Mirela

AU - Mody, Nimesh

N1 - Acknowledgments The authors thank J.R. Speakman (UoA) for invaluable discussion regarding energy expenditure, T. Martin (Johnson & Johnson, NJ) and U. Thurneer (Cilag AG, Switzerland) for fenretinide, to use completely without restriction or obligation, and undergraduate student K. Towle (UoA) for assisting in experiments. Funded by British Heart Foundation Intermediate Basic Research Fellowship. Grant Number: FS/09/026 Research Councils UK Fellowship European Foundation for the Study of Diabetes (EFSD)/Lilly Biotechnology and Biological Sciences Research Council (BBSRC) studentship University of Aberdeen (UoA) Centre for Genome-Enabled Biology & Medicine (CGEBM) studentship BBSRC. Grant Number: BB/G014272/1

PY - 2015/8

Y1 - 2015/8

N2 - ObjectiveThe synthetic retinoid Fenretinide (FEN) inhibits adiposity in male mice fed a high-fat-diet (HFD) in association with alterations in retinoic acid (RA)-signaling. Young female mice are protected from obesity via estrogen-signaling. We therefore investigated whether FEN also influences adiposity in aged female mice differing in parity, and whether such effects are mediated by retinoid and estrogen-signaling. Design and MethodsAged nulliparous and parous female mice were maintained on HFD±FEN and adiposity was assessed. Quantitative-PCR was performed on white adipose tissue (WAT), liver and 3T3-L1 adipocytes treated with RA or FEN±estrogen.ResultsParous females were more obese than nulliparous mice independent of age. FEN-HFD prevented the HFD-induced increase in adiposity and leptin levels independently of parity. FEN-HFD induced retinoid-responsive genes in WAT and liver. Parous females had reduced expression of hepatic estrogen-responsive genes but FEN-HFD up-regulated WAT Cyp19a1 and Esr2 in parous mice. Estrogen and RA acted synergistically to increase RA-receptor (RAR)-mediated gene expression in 3T3-L1 adipocytes. FEN increased Cyp19a1 and Esr2, similar to our findings in vivo. ConclusionsThe prevention of adiposity by FEN in response to HFD in female mice appears to involve increased retinoid-signaling in association with induction of local estrogen production and estrogen-signaling in WAT.

AB - ObjectiveThe synthetic retinoid Fenretinide (FEN) inhibits adiposity in male mice fed a high-fat-diet (HFD) in association with alterations in retinoic acid (RA)-signaling. Young female mice are protected from obesity via estrogen-signaling. We therefore investigated whether FEN also influences adiposity in aged female mice differing in parity, and whether such effects are mediated by retinoid and estrogen-signaling. Design and MethodsAged nulliparous and parous female mice were maintained on HFD±FEN and adiposity was assessed. Quantitative-PCR was performed on white adipose tissue (WAT), liver and 3T3-L1 adipocytes treated with RA or FEN±estrogen.ResultsParous females were more obese than nulliparous mice independent of age. FEN-HFD prevented the HFD-induced increase in adiposity and leptin levels independently of parity. FEN-HFD induced retinoid-responsive genes in WAT and liver. Parous females had reduced expression of hepatic estrogen-responsive genes but FEN-HFD up-regulated WAT Cyp19a1 and Esr2 in parous mice. Estrogen and RA acted synergistically to increase RA-receptor (RAR)-mediated gene expression in 3T3-L1 adipocytes. FEN increased Cyp19a1 and Esr2, similar to our findings in vivo. ConclusionsThe prevention of adiposity by FEN in response to HFD in female mice appears to involve increased retinoid-signaling in association with induction of local estrogen production and estrogen-signaling in WAT.

KW - Female Mice

KW - Aged

KW - Fenretinide

KW - Obesity

KW - Retinoid

KW - Estrogen

U2 - 10.1002/oby.21164

DO - 10.1002/oby.21164

M3 - Article

SN - 1930-7381

VL - 23

SP - 1655

EP - 1662

JO - Obesity

JF - Obesity

IS - 8

ER -

Fenretinide prevents obesity in aged female mice in association with increased retinoid and estrogen-signaling

Abstract

Bibliographical note

Keywords

UN SDGs

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Peter McCaffery

Nimesh Mody

Centre for Genome-Enabled Biology and Medicine

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Fenretinide prevents obesity in aged female mice in association with increased retinoid and estrogen-signaling

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Bibliographical note

Keywords

UN SDGs

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Nimesh Mody

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