Arcuate nucleus homeostatic systems reflect blood leptin concentration but not feeding behaviour during scheduled feeding on a high-fat diet in mice

T. Bake, J. Baron, J. S. Duncan, D. G. A. Morgan, J. G. Mercer

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Abstract

Hypothalamic homeostatic and forebrain reward-related genes were examined in the context of scheduled meal feeding without caloric restriction in C57BL/6 mice. Mice fed ad libitum but allowed access to a palatable high fat diet for 2 h a day rapidly adapted their feeding behaviour and consumed approximately 80% of their daily caloric intake during this 2 h scheduled feed. Gene expression levels were examined during either the first or second hour of scheduled feeding vs. 24 h ad libitum feeding on the same high fat diet. Gene expression of neuropeptide Y, agouti-related peptide, cocaine- and amphetamine-regulated transcript, proopiomelanocortin, long-form leptin receptor and suppressor of cytokine signalling-3 in the hypothalamic arcuate nucleus (ARC), and enkephalin, dynorphin, dopamine-2-receptor and dopamine-3-receptor in the nucleus accumbens (NAcc) in the forebrain were measured by in situ hybridisation. Mice fed ad libitum on high fat diet had the highest total caloric intake, body weight gain, fat mass and serum leptin, whereas schedule-fed mice had a mild obese phenotype with intermediate total caloric intake, body weight gain, fat mass and serum leptin. The effects of feeding regime on ARC gene expression were emphasised by significant positive or negative correlations with body weight gain, fat mass and blood leptin, but did not appear to be related to feeding behaviour in the schedule-fed groups, i.e. the large, binge-type meals, and did not reveal any potential candidates for the regulation of these meals. Mechanisms underlying large meal/binge-type eating may be regulated by non-homeostatic hedonic processes. However, assessment of opioid and dopamine receptor gene expression in the NAcc did not reveal evidence of involvement of these genes in regulating the large meals. This complements our previous characterisation of ARC and NAcc genes in schedule-fed mice and rats, but still leaves open the fundamental question about the underlying mechanisms of meal feeding.
Original languageEnglish
Article numbere12498
JournalJournal of Neuroendocrinology
Volume29
Issue number8
Early online date27 Jun 2017
DOIs
Publication statusPublished - Aug 2017

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Arcuate Nucleus of Hypothalamus
High Fat Diet
Feeding Behavior
Leptin
Meals
Dopamine Receptors
Nucleus Accumbens
Energy Intake
Weight Gain
Gene Expression
Appointments and Schedules
Fats
Body Weight
Prosencephalon
Genes
Leptin Receptors
Dynorphins
Caloric Restriction
Pro-Opiomelanocortin
Bulimia

Keywords

  • scheduled feeding
  • palatable diet
  • binge-type eating
  • energy balance gene expression
  • mice

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Arcuate nucleus homeostatic systems reflect blood leptin concentration but not feeding behaviour during scheduled feeding on a high-fat diet in mice. / Bake, T.; Baron, J.; Duncan, J. S.; Morgan, D. G. A.; Mercer, J. G.

In: Journal of Neuroendocrinology, Vol. 29, No. 8, e12498, 08.2017.

Research output: Contribution to journalArticle

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note = "Acknowledgements T.B. was funded by a CASE studentship from the BBSRC and AstraZeneca. J.B. was a summer student from Bordeaux Sciences Agro and funded by student laboratory experience grant from the British Society of Neuroendocrinology. The authors are also grateful for funding from the Scottish Government, and from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreements 266408 (Full4Health) and 245009 (NeuroFAST).",
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N1 - Acknowledgements T.B. was funded by a CASE studentship from the BBSRC and AstraZeneca. J.B. was a summer student from Bordeaux Sciences Agro and funded by student laboratory experience grant from the British Society of Neuroendocrinology. The authors are also grateful for funding from the Scottish Government, and from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreements 266408 (Full4Health) and 245009 (NeuroFAST).

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N2 - Hypothalamic homeostatic and forebrain reward-related genes were examined in the context of scheduled meal feeding without caloric restriction in C57BL/6 mice. Mice fed ad libitum but allowed access to a palatable high fat diet for 2 h a day rapidly adapted their feeding behaviour and consumed approximately 80% of their daily caloric intake during this 2 h scheduled feed. Gene expression levels were examined during either the first or second hour of scheduled feeding vs. 24 h ad libitum feeding on the same high fat diet. Gene expression of neuropeptide Y, agouti-related peptide, cocaine- and amphetamine-regulated transcript, proopiomelanocortin, long-form leptin receptor and suppressor of cytokine signalling-3 in the hypothalamic arcuate nucleus (ARC), and enkephalin, dynorphin, dopamine-2-receptor and dopamine-3-receptor in the nucleus accumbens (NAcc) in the forebrain were measured by in situ hybridisation. Mice fed ad libitum on high fat diet had the highest total caloric intake, body weight gain, fat mass and serum leptin, whereas schedule-fed mice had a mild obese phenotype with intermediate total caloric intake, body weight gain, fat mass and serum leptin. The effects of feeding regime on ARC gene expression were emphasised by significant positive or negative correlations with body weight gain, fat mass and blood leptin, but did not appear to be related to feeding behaviour in the schedule-fed groups, i.e. the large, binge-type meals, and did not reveal any potential candidates for the regulation of these meals. Mechanisms underlying large meal/binge-type eating may be regulated by non-homeostatic hedonic processes. However, assessment of opioid and dopamine receptor gene expression in the NAcc did not reveal evidence of involvement of these genes in regulating the large meals. This complements our previous characterisation of ARC and NAcc genes in schedule-fed mice and rats, but still leaves open the fundamental question about the underlying mechanisms of meal feeding.

AB - Hypothalamic homeostatic and forebrain reward-related genes were examined in the context of scheduled meal feeding without caloric restriction in C57BL/6 mice. Mice fed ad libitum but allowed access to a palatable high fat diet for 2 h a day rapidly adapted their feeding behaviour and consumed approximately 80% of their daily caloric intake during this 2 h scheduled feed. Gene expression levels were examined during either the first or second hour of scheduled feeding vs. 24 h ad libitum feeding on the same high fat diet. Gene expression of neuropeptide Y, agouti-related peptide, cocaine- and amphetamine-regulated transcript, proopiomelanocortin, long-form leptin receptor and suppressor of cytokine signalling-3 in the hypothalamic arcuate nucleus (ARC), and enkephalin, dynorphin, dopamine-2-receptor and dopamine-3-receptor in the nucleus accumbens (NAcc) in the forebrain were measured by in situ hybridisation. Mice fed ad libitum on high fat diet had the highest total caloric intake, body weight gain, fat mass and serum leptin, whereas schedule-fed mice had a mild obese phenotype with intermediate total caloric intake, body weight gain, fat mass and serum leptin. The effects of feeding regime on ARC gene expression were emphasised by significant positive or negative correlations with body weight gain, fat mass and blood leptin, but did not appear to be related to feeding behaviour in the schedule-fed groups, i.e. the large, binge-type meals, and did not reveal any potential candidates for the regulation of these meals. Mechanisms underlying large meal/binge-type eating may be regulated by non-homeostatic hedonic processes. However, assessment of opioid and dopamine receptor gene expression in the NAcc did not reveal evidence of involvement of these genes in regulating the large meals. This complements our previous characterisation of ARC and NAcc genes in schedule-fed mice and rats, but still leaves open the fundamental question about the underlying mechanisms of meal feeding.

KW - scheduled feeding

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