A spoonful of sugar: feedback signals of energy stores and corticosterone regulate responses to chronic stress

Dallman, Mary F.; Akana, Susan F.; Laugero, Kevin D.; Gómez, Francisca; Manalo, Sotara; Bell, Michael; Bhatnagar, Seema

doi:10.1016/s0031-9384(03)00100-8

Cited by 112 publications

(81 citation statements)

References 57 publications

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“…Glucocorticoids play an important role in regulating proteins, carbohydrates, and fats (Dallman et al, 2003), and cortisol is elevated in response to falling blood glucose levels (Van Cauter et al, 1992). We observed that free fatty acid levels were higher in men and women after caffeine, as reported by others (Fisher et al, 1986).…”

Section: Discussionsupporting

confidence: 82%

Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women

Lovallo

Farag

Vincent

et al. 2006

Pharmacology Biochemistry and Behavior

152

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Caffeine elevates cortisol secretion, and caffeine is often consumed in conjunction with exercise or mental stress. The interactions of caffeine and stress on cortisol secretion have not been explored adequately in women. We measured cortisol levels at eight times on days when healthy men and women consumed caffeine (250 mg × 3) and underwent either mental stress or dynamic exercise protocols, followed by a midday meal, in a double blind, placebo-controlled, crossover design. Men and women had similar cortisol levels at the predrug baselines, but they responded differently to mental stress and exercise. The cortisol response to mental stress was smaller in women than in men (p=.003). Caffeine acted in concert with mental stress to further increase cortisol levels (p=.011), the effect was similar in men and women. Exercise alone did not increase cortisol, but caffeine taken before exercise elevated cortisol in both men and women (ps<.05). After a postexercise meal, the women had a larger cortisol response than the men, and this effect was greater after caffeine (p<.01). Cortisol release in response to stress and caffeine therefore appears to be a function of the type of stressor and the sex of the subject. However, repeated caffeine doses increased cortisol levels across the test day without regard to the sex of the subject or type of stressor employed (p<.00001). Caffeine may elevate cortisol by stimulating the central nervous system in men but may interact with peripheral metabolic mechanisms in women.

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Section: Discussionsupporting

confidence: 82%

Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women

Lovallo

Farag

Vincent

et al. 2006

Pharmacology Biochemistry and Behavior

152

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“…Conversely, liver-specific deletion of 11␤-HSD1 increases adrenal size, suggesting HPA axis activation, consistent with a role for peripheral 11␤-HSD1 in control of the HPA axis (392). While the underlying basis for this is not fully established, it is known that sugars and perhaps other fuel substrates impact on the HPA axis (139,374,387), and an afferent hepatic pathway via the vagus nerve also modulates HPA axis function (375). The notion that liver metabolism of glucocorticoids controls the stress axis is intriguing, plausibly representing a key node in the intimate association between the key organ determining metabolic fuel availability and the major neuroendocrine control of fuel homeostasis.…”

Section: Endocrine Effects Of Hepatic 11␤-hsd1mentioning

confidence: 74%

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Chapman

Holmes

Seckl

2013

Physiological Reviews

713

601

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Glucocorticoid action on target tissues is determined by the density of “nuclear” receptors and intracellular metabolism by the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) which catalyze interconversion of active cortisol and corticosterone with inert cortisone and 11-dehydrocorticosterone. 11β-HSD type 1, a predominant reductase in most intact cells, catalyzes the regeneration of active glucocorticoids, thus amplifying cellular action. 11β-HSD1 is widely expressed in liver, adipose tissue, muscle, pancreatic islets, adult brain, inflammatory cells, and gonads. 11β-HSD1 is selectively elevated in adipose tissue in obesity where it contributes to metabolic complications. Similarly, 11β-HSD1 is elevated in the ageing brain where it exacerbates glucocorticoid-associated cognitive decline. Deficiency or selective inhibition of 11β-HSD1 improves multiple metabolic syndrome parameters in rodent models and human clinical trials and similarly improves cognitive function with ageing. The efficacy of inhibitors in human therapy remains unclear. 11β-HSD2 is a high-affinity dehydrogenase that inactivates glucocorticoids. In the distal nephron, 11β-HSD2 ensures that only aldosterone is an agonist at mineralocorticoid receptors (MR). 11β-HSD2 inhibition or genetic deficiency causes apparent mineralocorticoid excess and hypertension due to inappropriate glucocorticoid activation of renal MR. The placenta and fetus also highly express 11β-HSD2 which, by inactivating glucocorticoids, prevents premature maturation of fetal tissues and consequent developmental “programming.” The role of 11β-HSD2 as a marker of programming is being explored. The 11β-HSDs thus illuminate the emerging biology of intracrine control, afford important insights into human pathogenesis, and offer new tissue-restricted therapeutic avenues.

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“…Energy homeostasis is enabled by peripheral signals informing the CNS about energy storage levels and metabolic status. Vagal afferents and hormones including leptin, insulin, ghrelin, and glucocorticoids relay this interoceptive information to hypothalamic and brainstem nuclei that in turn regulate energy consumption, utilization, and storage (2,3). Peripheral information processed centrally is used to elicit appropriate feeding, endocrine, and autonomic motor responses.…”

Section: Introductionmentioning

confidence: 99%

“…Anterior lobe corticotrophs secrete ACTH that stimulates the production of glucocorticoids from the adrenals. Therefore, a disruption in pituitary POMC function could impact energy balance secondarily via altered levels of glucocorticoid hormones, which regulate metabolism, fat distribution, and the development of obesity independently of αMSH (3). Corticosterone is known to play a permissive role in rodents for positive energy balance.…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoids exacerbate obesity and insulin resistance in neuron-specific proopiomelanocortin-deficient mice

Smart¹

2006

Journal of Clinical Investigation

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Null mutations of the proopiomelanocortin gene (Pomc -/-) cause obesity in humans and rodents, but the contributions of central versus pituitary POMC deficiency are not fully established. To elucidate these roles, we introduced a POMC transgene (Tg) that selectively restored peripheral melanocortin and corticosterone secretion in Pomc -/-mice. Rather than improving energy balance, the genetic replacement of pituitary POMC in Pomc -/-Tg + mice aggravated their metabolic syndrome with increased caloric intake and feed efficiency, reduced oxygen consumption, increased subcutaneous, visceral, and hepatic fat, and severe insulin resistance. Pair-feeding of Pomc -/-Tg + mice to the daily intake of lean controls normalized their rate of weight gain but did not abolish obesity, indicating that hyperphagia is a major but not sole determinant of the phenotype. Replacement of corticosterone in the drinking water of Pomc -/-mice recapitulated the hyperphagia, excess weight gain and fat accumulation, and hyperleptinemia characteristic of genetically rescued Pomc -/-Tg + mice. These data demonstrate that CNS POMC peptides play a critical role in energy homeostasis that is not substituted by peripheral POMC. Restoration of pituitary POMC expression to create a de facto neuronal POMC deficiency exacerbated the development of obesity, largely via glucocorticoid modulation of appetite, metabolism, and energy partitioning. IntroductionDeciphering the complex regulatory mechanisms for energy balance is a health-care priority because of the rapidly growing prevalence of obesity (1). Energy homeostasis is enabled by peripheral signals informing the CNS about energy storage levels and metabolic status. Vagal afferents and hormones including leptin, insulin, ghrelin, and glucocorticoids relay this interoceptive information to hypothalamic and brainstem nuclei that in turn regulate energy consumption, utilization, and storage (2, 3). Peripheral information processed centrally is used to elicit appropriate feeding, endocrine, and autonomic motor responses.Neurons in the arcuate nucleus of the hypothalamus that express the gene encoding proopiomelanocortin (POMC) play a major role in this physiological network (4-6). Genetic disruption of either the mouse Pomc or the human POMC gene causes early-onset obesity (7-9), suggesting that endogenous POMC pathways are essential for the regulation of energy homeostasis. POMC is processed posttranslationally to the endogenous opioid β-endorphin and the melanocortin peptides ACTH, α-melanocyte-stimulating hormone (αMSH), βMSH, and γMSH. Absence of some or all of these peptides could potentially contribute to the obesity syndrome. In the CNS, energy balance is profoundly modulated by the anorexigenic peptide αMSH via melanocortin receptor-4 (MC4-R) activation. Central administration of αMSH (10, 11) or a synthetic analog, MTII (12, 13), reduces food intake in rodents. Conversely, mutations of MC4-R, the most abundant melanocortin receptor

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A spoonful of sugar: feedback signals of energy stores and corticosterone regulate responses to chronic stress

Cited by 112 publications

References 57 publications

Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women

Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Glucocorticoids exacerbate obesity and insulin resistance in neuron-specific proopiomelanocortin-deficient mice

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