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Feast and Famine: Critical Role of Glucocorticoids with Insulin in Daily Energy Flow
Abstract
The hypothesis proposed in this review is that normal diurnal rhythms in the hypothalamic-pituitary-adrenal (HPA) axis are highly regulated by activity in medial hypothalamic nuclei to effect an interaction between corticosteroids and insulin such that optimal metabolism results in response to changes in the fed or fasted state of the animal. There are marked diurnal rhythms in function of the HPA axis under both basal and stress conditions. The HPA axis controls corticosteroid output from the adrenal and, in turn, forward elements of this axis are inhibited by feedback from circulating plasma corticosteroid levels. Basal activity in the HPA axis of mammals fed ad lib peaks about 2 h before the peak of the diurnal feeding rhythm, and is controlled by input from the suprachiasmatic nuclei. The rhythm in stress responsiveness is lowest at the time of the basal peak and highest at the time of the basal trough in the HPA axis activity. There are also diurnal rhythms in corticosteroid feedback sensitivity of basal and stress-induced ACTH secretion which peak at the time of the basal trough. These rhythms are all overridden when feeding, and thus insulin secretion, is disrupted. Corticosteroids interact with insulin on food intake and body composition, and corticosteroids also increase insulin secretion. Corticosteroids stimulate feeding at low doses but inhibit it at high doses; however, it is the high levels of insulin, induced by high levels of corticosteroids, that may inhibit feeding. The effects of corticosteroids on liver, fat, and muscle cell metabolism, with emphasis on their interactions with insulin, are briefly reviewed. Corticosteroids both synergize with and antagonize the effects of insulin. The effects of stress hormones, and their interactions with insulin on lipid and protein metabolism, followed by some of the metabolic effects of injury stress, with or without nutritional support, are evaluated. In the presence of elevated insulin stimulated by glucocorticoids and nutrition, stress causes less severe catabolic effects. In the central nervous system, regulation of function in the HPA axis is clearly affected by the activity of medial hypothalamic nuclei that also alter feeding, metabolism, and obesity in rats. Lesions of the arcuate (ARC) and ventromedial (VMN) paraventricular (PVN) nuclei result in obesity and hyperactivity in the HPA axis. Moreover, adrenalectomy inhibits or prevents development of the lesion-induced obesity. There are interactions among these nuclei; one mode of communication is via inputs of neuropeptide Y (NPY) cells in the ARC to the VMN, dorsomedial nuclei, and PVN.(ABSTRACT TRUNCATED AT 400 WORDS)
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“Similarly, stress has been shown to be associated with increased appetite (Dallman et al., 1993)”
From The impact of stress on students in secondary school and higher education (2020) · cites this paper as Dallman et al., 1993
In the citing paper
“In fact, experimentally increasing late-afternoon and early-evening cortisol through hydrocortisone administration induces insulin resistance the following day [69, 73, 74].”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [69]
In the citing paper
“These findings are highly relevant because hypercortisolemia during the late-afternoon and early-evening is harmful, and is believed to cause the insulin resistance observed with advanced age [60, 69, 70], impair physical performance [71] and trigger neurocognitive deficits [72].”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [69]
In the citing paper
“Administration of glucocorticoids to bolster cortisol levels in the late afternoon and early evening also induces insulin resistance [69, 73, 74] through post-receptor mechanisms [90–92].”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [69]
In the citing paper
“Raised cortisol concentrations in the evening are thought to contribute to age-related insulin resistance [55], [56].”
From Impact of Five Nights of Sleep Restriction on Glucose Metabolism, Leptin and Testosterone in Young Adult Men (2012) · cites this paper as [55]
In the citing paper
“Circadian misalignment may lead to central and peripheral deleterious consequences, such as memory deficit and insulin resistance [69–71].”
From Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity (2010) · cites this paper as [70]
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“Based on their theory that circadian rhythms of feeding are associated with circadian rhythm of the HPA axis [ 3 ], Hanson et al. studied HPA axis responses of rats to 30 min of physical restraint either after a 17-h fast during the activity period (during the night) or fed ad libitum.”
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“(Dallman et al., 1993), leading to a balanced system to provide energy to the organism (Adam and Epel, 2007).”
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“While the effects of chronically elevated CORT on such measures have been well-studied in birds and other vertebrates, comparatively little is known about the effects of repeated, acute elevations of CORT (Table 1; Dallman et al., 1993; Sapolsky et al., 2000; Wingfield and Romero, 2001).”
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“However, CORT is also a potent stimulator of food intake (Wingfield et al., 1990; Dallman et al., 1993; Landys et al., 2004b; La Fleur, 2006; Landys et al., 2006), and this effect could either augment or detract from nestling provisioning efforts.”
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“Food restriction and food intake recruit a variety of stress- and energy status-related hormonal signals (Dallman et al., 1993; Gao and Horvath, 2007).”
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“Lipogenesis (Gray et al. 1990; Dallman et al. 1993 ) and migratory fattening through hyperphagia (Holberton et al. 1996; Holberton 1999; Peirsma et al. 2000) have been closely linked to CORT production in migratory birds.”
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“Trunk blood plasma corticosterone levels were similar in SHAM and CORT rats (Fig. 1), and elevated relative to the normal circadian mean ( 26 , 27).”
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Immunoendocrine Alterations during Human Tuberculosis as an Integrated View of Disease Pathology
Bottasso, O. A., Bay, M. L., Besedovsky, H. O., & del Rey, A. (2009) · NeuroImmunoModulation · doi:10.1159/000180261 · Cited by 33
“Adrenal steroids, in particular GCs, may partly account for the weight loss observed. GCs mobilize lipids by stimulating the activity of a hormone-sensitive lipoprotein lipase, and therefore inducing lipolysis in fat cells. GCs also inhibit protein synthesis and stimulate proteolysis in various muscle types [”
BackgroundQuirici, V., Venegas, C. I., González‐Gómez, P. L., et al. (2014) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2013.12.010 · Cited by 33
“Glucocorticoids are essential for life as they regulate or support a variety of important cardiovascular, metabolic, immunologic, and maintain daily homeostatic energetic balance (Harvey et al., 1984; Dallman et al., 1993).”
BackgroundAdverse neuro-immune–endocrine interactions in patients with active tuberculosis
Bottasso, O. A., Bay, M. L., Besedovsky, H. O., & del Rey, A. (2012) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2012.11.002 · Cited by 32
“, 2011), increased cortisol in TB patients may favor the loss of body mass, since the hormone mobilizes lipid stores by inducing lipolysis in fat cells inhibiting protein synthesis and stimulating proteolysis in muscle cells (Dallman et al., 1993).”
D’Attilio, L., Santucci, N. E., Bongiovanni, B., Bay, M. L., & Bottasso, O. A. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00214 · Cited by 36
“Also, GCs inhibit protein synthesis and stimulate proteolysis in muscle cells (40), in addition to reducing food intake and inducing body weight loss, probably via increased hypothalamic CRH levels, which seems to be catabolic (41).”
BackgroundUsing the van Noordwijk and de Jong Resource Framework to Evaluate Glucocorticoid-Fitness Hypotheses
Breuner, C. W., & Berk, S. A. (2019) · Integrative and Comparative Biology · doi:10.1093/icb/icz088 · Cited by 33
Lifestyle mediators of associations among siestas, obesity, and metabolic health
Vizmanos-Lamotte, B., Cascales, A. I., Rodríguez‐Martín, M., Salmerón, D., Morales, E., Alonso, A. A., Scheer, F. A. J. L., & Garaulet, M. (2023) · Obesity · doi:10.1002/oby.23765 · Cited by 34
“In addition, the increase in CAR after napping [33] may help explain why 42% of the current population were hungry when awakening from a siesta, given the role of cortisol in motivating food intake [35].”
BackgroundFunctional genomics of the muscle response to restraint and transport in chickens1
Hazard, D., Fernandez, X., Pinguet, J., Chambon, C., Létisse, F., Portais, J., Wadih-Moussa, Z., Rémignon, H., & Molette, C. (2011) · Journal of Animal Science · doi:10.2527/jas.2010-3288 · Cited by 33
“Catecholamines and glucocorticoids have been reported to have a critical role in metabolic changes induced by stress (Dallman et al., 1993), and more particularly to increase the use of energy stores during the stress response (Coderre et al., 1991; Sapolsky et al., 2000).”
BackgroundMethodPecoraro, N. C., de Jong, H. K., & Dallman, M. F. (2009) · Physiology & Behavior · doi:10.1016/j.physbeh.2008.12.018 · Cited by 34
Self-citationCollado, V., Hennèquin, M., Faulks, D., Mazille, M.-N., Nicolas, E., Koscielny, S., & Onody, P. (2006) · Journal of Clinical Psychopharmacology · doi:10.1097/01.jcp.0000236660.01039.eb · Cited by 32
Challenges in researching the immune pathways between early life adversity and psychopathology
Reid, B. M., & Danese, A. (2020) · Development and Psychopathology · doi:10.1017/s0954579420001157 · Cited by 37
“The neuroendocrine pathway between ELA, obesity, and inflammation could be a potent one, as glucocorticoids contribute to adipose tissue development (Dallman et al., 1993) and cortisol plays a central role in regulating food intake and metabolism (Dallman, 2010; Dallman, Pecoraro, & la Fleur, 2005).”
BackgroundWolkow, A. P., Aisbett, B., Reynolds, J., Ferguson, S. A., & Main, L. C. (2015) · International Archives of Occupational and Environmental Health · doi:10.1007/s00420-015-1085-3 · Cited by 36
Ayyar, V. S., Almon, R. R., Jusko, W. J., & DuBois, D. C. (2015) · Physiological Reports · doi:10.14814/phy2.12382 · Cited by 34
“They play a major role in regulating the production, storage, use, and distribution of substrates for systemic energy metabolism (Dallman et al. 1993).”
BackgroundShridas, P., Bailey, W. M., Boyanovsky, B. B., Oslund, R., Gelb, M. H., & Webb, N. R. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.090423 · Cited by 32
Nyberg, C. H. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.06.002 · Cited by 33
“Finally, the metabolic actions of cortisol are numerous, and range from the mobilization of energy reserves via gluconeogenesis and lipolysis, to the intracellular modulation of ATP production (Brillon et al., 1995; Du et al., 2009; Dallman et al., 1993; Hershberger et al., 2004).”
BackgroundChronic stress--the key to parturition?
McMillen, I. C., Phillips, I., Ross, J. T., Robinson, J. S., & Owens, J. A. (1995) · Reproduction Fertility and Development · doi:10.1071/rd9950499 · Cited by 32
The application of allostasis and allostatic load in animal species: A scoping review
Seeley, K. E., Proudfoot, K. L., & Edes, A. N. (2022) · PLoS ONE · doi:10.1371/journal.pone.0273838 · Cited by 37
D’Alba, L., Spencer, K. A., Nager, R. G., et al. (2011) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2011.03.006 · Cited by 31
The inhibitory effect of hormones associated with stress on Na appetite of sheep
Weisinger, R. S., Blair-West, J. R., Burns, P. L., Denton, D. A., McKinley, M. J., Purcell, B. S., Vale, W. W., Rivier, J., & Sunagawa, K. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.040577997 · Cited by 31
Endocrine regulation of food intake and body weight
Figlewicz, D. P., Schwartz, M. W., Seeley, R. J., Chavez, M., Baskin, D. G., Woods, S. C., & Porte, D. (1996) · Journal of Laboratory and Clinical Medicine · doi:10.1016/s0022-2143(96)90179-1 · Cited by 30
Metadata
- Authors
- Dallman, M. F., Strack, A. M., Akana, S. F., Bradbury, M. J., Hanson, E. S., Scribner, K. A., & Smith, M.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Frontiers in Neuroendocrinology
- Publisher
- Elsevier BV
- Published
- 1993-10
- Volume
- 14
- Issue
- 4
- Pages
- 303-347
- ISSN
- 0091-3022 (ISSN-L)
- OpenAlex
- W1971922927
- Cited by
- 796
- References
- 0
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 12 · 2023: 21 · 2022: 15 · 2021: 20 · 2020: 22 · 2019: 22 · 2018: 13 · 2017: 13 · 2016: 30 · 2015: 26 · 2014: 27 · 2013: 20 · 2012: 33
- FWCI
- 6.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Frontiers in Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK28172)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- glucocorticoids, insulin, hypothalamic-pituitary-adrenal axis, diurnal cycle, feeding behavior, stress hormones, corticosteroid feedback, ACTH secretion, arcuate nucleus, neuropeptide Y, obesity, energy metabolism, lipid metabolism, protein metabolism, catabolism, adrenalectomy, body composition
- MeSH terms
- Animals, Circadian Rhythm, Eating, Energy Metabolism, Fasting, Feeding Behavior, Glucocorticoids, Humans, Hypothalamo-Hypophyseal System, Insulin, Pituitary-Adrenal System, Stress, Physiological, Rats
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