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Allopregnanolone preferentially induces energy-rich food intake in male Wistar rats
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. (UNC)
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
2014 (English)In: Physiological Reports, E-ISSN 2051-817X, Vol. 2, no 12, e12190- p.Article in journal (Refereed) Published
Abstract [en]

Obesity is an increasing problem and identification of the driving forces for overeating of energy-rich food is important. Previous studies show that the stress and sex steroid allopregnanolone has a hyperphagic effect on both bland food and palatable food. If allopregnanolone induces a preference for more palatable or for more energy-rich food is not known. The aim of this study  was to elucidate the influence of allopregnanolone on food preference. Male Wistar rats were subjected to two different food preference tests: a choice between standard chow and cookies (which have a higher energy content and also are more palatable than chow), and a choice between a low caloric sucrose solution and standard chow (which has a higher energy content and is less palatable than sucrose). Food intake was measured for 1 h after acute subcutaneous injections of allopregnanolone. In the choice between cookies and chow allopregnanolone significantly increased only the intake of cookies.When the standard chow was the item present with the highest caloric load, the chow intake was increased and allopregnanolone had no effect on intake of the 10% sucrose solution. The increased energy intakes induced by the high allopregnanolone dose compared to vehicle were very similar in the two tests,120% increase for cookies and 150% increase for chow. It appears that in allopregnanolone-induced hyperphagia, rats choose the food with the highest energy content regardless of its palatability.

Place, publisher, year, edition, pages
Wiley Periodicals Inc. , 2014. Vol. 2, no 12, e12190- p.
Keyword [en]
Allopregnanolone, energy need, food intake, neurosteroids GABA
National Category
Neurosciences Physiology
URN: urn:nbn:se:umu:diva-101791DOI: 10.14814/12190OAI: diva2:802595
Available from: 2015-04-13 Created: 2015-04-13 Last updated: 2015-04-16Bibliographically approved
In thesis
1. Allopregnanolone effects on food intake and weight gain
Open this publication in new window or tab >>Allopregnanolone effects on food intake and weight gain
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background Obesity is currently one of the major causes of ill health and it is clear that overeatingis the cause of obesity. However, the actions of many endogenous factors that contribute to overeating are still not well understood. Gamma-aminobutyric acid (GABA)-ergic transmission has been shown to be of great importance for food intake regulation. The progesterone metabolite allopregnanolone is a potent positive GABAA receptor modulating steroid (GAMS) and in humans, elevated allopregnanolone levels have been suggested to be involved in increased food intake, and also with overweight and obesity. GABAA receptors that express the α2 and α3 subunits are proposed to be the main subtypes involved in food intake regulation. Therefore, the aims of the work in this thesis were to further investigate the effect of allopregnanolone on food intake, feeding behaviour, possible effects on weight gain and also to characterize a possible antagonist at α2β3γ2and α3β3γ2 GABAA receptors.

Methods Allopregnanolone effects on food intake of different food items were recorded in male Wistar rats. Feeding patterns were analyzed. Food preference tests were also conducted and rats were repeatedly exposed to allopregnanolone under different feeding conditions to elucidate possible effects on body weight gain. To deeper investigate GABAA receptor subtypes suggested to be involved in food intake regulation, electrophysiological whole-cell patch-clamp recordings were performed to identify the specificity of the GAMS antagonist UC1020, at human α2β3γ2 and α3β3γ2 GABAA receptors expressed in HEK293-cells.

Results Allopregnanolone increased the intake of standard chow, cookies and a high fat diet in male Wistar rats. Preferentially, allopregnanolone increased the rats´intake of the more calorie dense food type. Allopregnanolone reduced feeding latency and prolonged feeding duration. The increased chow intake induced by allopregnanolone was more pronounced at the beginning of the rats´ active period compared to the inactive. Repeated allopregnanolone administration during 5 consecutive days led to an increased body weight gain, more evident in schedule fed rats on a high fat diet. Both obesity prone and obesity resistant rats gained significantly more weight with repeated allopregnanolone exposure and the increased body weight gain correlated with increased food intake. The compound UC1020 was a potent antagonist of GAMS-enhanced GABA evoked currents at human α3β3γ2 GABAA receptors, whereas it had no effect at α2β3γ2 GABAA receptors.

Conclusions Our findings indicate that allopregnanolone induced hyperphagia may be one of the endogenous factors involved in weight gain, especially when the diet is energy-rich. The compound UC1020 may prove useful for investigating the involvement of the α2 and α3 GABAA receptor subtypes in GAMS-induced hyperphagia.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2015. 88 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1711
allopregnanolone, neurosteroid, GABA, GABAA receptor, food intake, weight gain, obesity, hyperphagia, diurnal rhythm, schedule feeding, high fat diet, electrophysiology
National Category
Neurosciences Physiology Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
urn:nbn:se:umu:diva-101806 (URN)978-91-7601-253-6 (ISBN)
Public defence
2015-05-13, Hörsal Betula, Norrlands universitetssjukhus, Umeå universitet, Umeå, 09:00 (Swedish)
Swedish Research Council, 4x-11198
Available from: 2015-04-22 Created: 2015-04-13 Last updated: 2015-05-04Bibliographically approved

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