(18) Fenretinide treatment for high fat diet-induced obesity and insulin sensitivity

Claire Henderson, Nimesh Mody

Research output: Contribution to journalArticle

Abstract

Introduction:
With‘the obesity epidemic’ever increasing, commonly associated pathologies, loosely termed the metabolic syndrome, are escalating at almost the same rate. Higher calorific intake and decreased activity levels contribute to both the development of obesity and its complications: e.g. hyperglycaemia, insulin resistance and hyperlipidaemia all contribute to cardiovascular disease. The synthetic retinoid, Fenretinide, has previously been demonstrated to slow obesity progression and improve insulin sensitivity in male mice without affecting food intake.
Aim:
To investigate the effects of Fenretinide, in high fat diet-induced obesity and insulin sensitivity in female mice.
Methods:
Nulliparous and parous female C57BL6 mice were studied o nCHOW, high fat (either 45% or 55%) or 45% high fat diet with Fenretinide incorporated. Body composition, blood glucose and hepatic protein expression were also investigated.
Results:
Nulliparous mice were shown to be protected against severe high fat diet-induced obesity. Strikingly, Fenretinide treatment caused parous mice to maintain a similar weight to those on a normal diet. Adiposity was found to be lower in all Fenretinide treated mice. Insulin sensitivity did not appear to be impaired in female mice however mice on 55% high fat diet did exhibit mild signs of insulin resistance. Molecular results suggested Fenretinide may function through modulation of the retinoic acid pathway.
Conclusion: Fenretinide treatment appears to protect against high fat diet-induced obesity in female mice. Insulin resistance was not present in obese females in contrast to previous obesity studies in male mice. The exact mechanism through which Fenretinide functions is still unknown.
Original languageEnglish
Pages (from-to)532
Number of pages1
JournalAtherosclerosis
Volume223
Issue number2
Early online date1 Aug 2012
DOIs
Publication statusPublished - Aug 2012

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