Gene Profiling Reveals a Role for Stress Hormones in the Molecular and Behavioral Response to Food Restriction

Guarnieri, Douglas J.; Brayton, Catherine E.; Richards, Sarah; Maldonado-Avilés, Jaime G.; Trinko, Richard; Nelson, Jessica C.; Taylor, Jane R.; Gourley, Shannon L.; DiLeone, Ralph J.

doi:10.1016/j.biopsych.2011.06.028

Cited by 48 publications

(37 citation statements)

References 60 publications

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“…Second, increased adiposity per se may influence both basal and acute HPA function. Unfortunately it was not feasible to account for differences in adiposity between the WT and HOM rats with ‘pair-feeding’ or caloric restriction, since these have significant effects on stress responses (Flak et al, 2011; Guarnieri et al, 2012) and would influence the stress system unevenly across the groups. Importantly however, when we performed these studies at 9 weeks of age, there was no significance difference in the body weights of WT and HET rats (Fig 1).…”

Section: Discussionmentioning

confidence: 99%

Loss of melanocortin-4 receptor function attenuates HPA responses to psychological stress

Ryan

Mul

Clemmensen

et al. 2014

Psychoneuroendocrinology

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SUMMARY The melanocortin 4 receptor (MC4R), well-known for its role in the regulation of energy balance, is widely expressed in stress-regulatory brain regions, including the paraventricular nucleus of the hypothalamus (PVH) and the medial amygdala (MeA). In agreement with this, MC4R has been implicated in hypothalamic-pituitary-adrenocortical axis (HPA) regulation. The present work investigated the role of chronic Mc4r function to modulate basal HPA axis tone and to facilitate acute HPA responses to psychological stress, using a novel rat model with Mc4r loss-of-function. In this study, adult male rats were placed into 3 groups (n=15/group) according to genotype [wild-type (WT); heterozygous mutant (HET); and homozygous mutant (HOM)]. Basal (pre-stress) plasma adrenocorticotropic hormone (ACTH) and corticosterone were measured in the AM and PM, and the HPA axis response to restraint was assessed in the AM. Rats were perfused at 2 hours after restraint to assess the effect of loss of MC4R on stress-induced c-Fos immunolabeling in stress-regulatory brain regions. We find that basal (non-stress) AM and PM plasma ACTH and corticosterone showed a normal diurnal rhythm that was not altered according to genotype. Consistent with this, adrenal and thymus weights were unaffected by genotype. However, the plasma ACTH and corticosterone responses to restraint were significantly reduced by loss of MC4R function. Likewise, stress-induced c-Fos immunolabeling in both PVH and MeA was significantly reduced by loss of Mc4r function. These results support the hypothesis that endogenous MC4R signaling contributes to the HPA axis response to stress. Because MC4R plays a critical role in the regulation of energy balance, the present work suggests that it may also serve as an important communication link between brain metabolic and stress systems.

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Section: Discussionmentioning

confidence: 99%

Loss of melanocortin-4 receptor function attenuates HPA responses to psychological stress

Ryan

Mul

Clemmensen

et al. 2014

Psychoneuroendocrinology

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“…In addition, tests that require food deprivation, such as the radial arm maze, would introduce the stress of food deprivation into the control cohorts. Indeed, food deprivation increases corticosterone levels in mice (32). We conclude from our study that CVS impaired, and sirtinol reversed, object location memory.…”

Section: Discussionmentioning

confidence: 99%

Sirtuin Activity in Dentate Gyrus Contributes to Chronic Stress-Induced Behavior and Extracellular Signal-Regulated Protein Kinases 1 and 2 Cascade Changes in the Hippocampus

Ferland

Hawley

Puckett

et al. 2013

Biological Psychiatry

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Background Exposure to chronic stress produces negative effects on mood and hippocampus-dependent memory formation. Alterations in signaling cascades and histone acetylation present a mechanism of modulation of transcription that may underlie stress-dependent processes in the hippocampus critical to learning and memory and development of depressive behaviors. Methods The rat model of chronic variable stress (CVS) was used to investigate the role of changes in protein acetylation and other molecular components of hippocampus-dependent memory formation and anhedonic behavior in response to CVS. Results Chronic variable stress treatment decreased both extracellular signal-regulated protein kinases 1 and 2 activation and Bcl-2 expression in all three regions of the hippocampus that corresponded behaviorally with a decrease in memory for the novel object location task and increased anhedonia. Extracellular signal-regulated protein kinases 1 and 2 activation was not significantly affected in the amygdala and increased in the medial prefrontal cortex by CVS. Chronic variable stress had no significant effect on activation of Akt in the hippocampus. We investigated molecular and behavioral effects of infusion of the sirtuin inhibitor, sirtinol, into the dentate gyrus (DG). Sirtinol infusion into the DG prevented the CVS-mediated decrease in extracellular signal-regulated protein kinases 1 and 2 activity and Bcl-2 expression, as well as histone acetylation in the DG previously observed following CVS. This corresponded to enhanced performance on the novel object location memory task, as well as reduced anhedonic behavior. Conclusions These results suggest that changes in sirtuin activity contribute to changes in molecular cascades and histone acetylation within the hippocampus observed following CVS and may represent a novel therapeutic target for stress-induced depression.

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“…For example, bilateral adrenalecomy reduces food intake, and GC administration increases food intake by stimulating the release of NPY and inhibiting CRF release (31). Furthermore, food restriction and high fat diets alter HPAaxis responses to stress and GC gene expression in a number of brain regions involved in energy homeostasis and stress (33), (20), (18), (34), (35). Thus, the hypothalamus is a critical region in the stress circuit as well as in the regulation of feeding and energy balance.…”

Section: The Overlapping Neurobiology Of Stress and Energy Homeostasismentioning

confidence: 99%

Stress as a Common Risk Factor for Obesity and Addiction

Sinha¹,

Jastreboff²

2013

Biological Psychiatry

471

356

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Stress is associated with obesity and the neurobiology of stress overlaps significantly with that of appetite and energy regulation. This review will discuss stress, allostasis, the neurobiology of stress and its overlap with neural regulation of appetite and energy homeostasis. Stress is a key risk factor in the development of addiction and in addiction relapse. High levels of stress changes eating patterns and augments consumption of highly palatable (HP) foods, which in turn, increases incentive salience of HP foods and allostatic load. The neurobiological mechanisms by which stress affects reward pathways to potentiate motivation and consumption of HP foods as well as addictive drugs is discussed. With enhanced incentive salience of HP foods and over-consumption of these foods, there are adaptations in stress and reward circuits that promote stress-related and HP food-related motivation as well as concomitant metabolic adaptations, including alterations in glucose metabolism, insulin sensitivity, and other hormones related to energy homeostatsis. These metabolic changes in turn may also affect dopaminergic activity to influence food motivation and intake of HP foods. An integrative heuristic model is proposed wherein repeated high levels of stress alter the biology of stress and appetite/energy regulation, with both components directly affecting neural mechanisms contributing to stress-induced and food cue-induced HP food motivation and engagement in overeating of such foods to enhance risk of weight gain and obesity. Future directions in research are identified to increase understanding of the mechanisms by which stress may increase risk of weight gain and obesity.

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Gene Profiling Reveals a Role for Stress Hormones in the Molecular and Behavioral Response to Food Restriction

Cited by 48 publications

References 60 publications

Loss of melanocortin-4 receptor function attenuates HPA responses to psychological stress

Loss of melanocortin-4 receptor function attenuates HPA responses to psychological stress

Sirtuin Activity in Dentate Gyrus Contributes to Chronic Stress-Induced Behavior and Extracellular Signal-Regulated Protein Kinases 1 and 2 Cascade Changes in the Hippocampus

Stress as a Common Risk Factor for Obesity and Addiction

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