Dose-Dependent Cortisol-Induced Increases in Plasma Leptin Concentration in Healthy Humans

Newcomer, John W.; Selke, Gregg; Melson, Angela K.; Gross, John B.; Vogler, George P.; Dagogo‐Jack, Samuel

doi:10.1001/archpsyc.55.11.995

Cited by 120 publications

(82 citation statements)

References 65 publications

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“…In vitro incubation of rat adipocytes with a synthetic GC, dexamethasone, increases leptin mRNA level and release as early as 2 h (8). Our laboratory (58) and others (36,56) find that, in humans, oral GCs increase leptin mRNA and serum leptin levels by approximately twofold, 24 -48 h after administration. Coadministration of a pulse of GCs with a meal or insulin increases serum leptin after 5-7 h, but it is not known whether this is because of an increase in leptin mRNA (34,35).…”

Section: Chronic Changes In Nutritional Status Regulate Leptin At Thementioning

confidence: 69%

Integration of hormonal and nutrient signals that regulate leptin synthesis and secretion

Lee¹,

Fried²

2009

American Journal of Physiology-Endocrinology and Metabolism

112

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Lee M-J, Fried SK. Integration of hormonal and nutrient signals that regulate leptin synthesis and secretion. Am J Physiol Endocrinol Metab 296: E1230 -E1238, 2009. First published March 24, 2009 doi:10.1152/ajpendo.90927.2008.-This review summarizes recent advances in our understanding of the pre-and posttranscriptional mechanisms that regulate leptin production and secretion in adipocytes. Basal leptin production is proportional to the status of energy stores, i.e., fat cell size, and this is mainly regulated by alterations in leptin mRNA levels. Leptin mRNA levels are regulated by hormones, including glucocorticoids and catecholamines, but little is known about the transcriptional mechanisms involved. Leptin synthesis and secretion is also acutely modulated in response to hormones such as insulin and the availability of metabolic fuels. Acute variations in leptin production over a time course of minutes to hours are mediated at the levels of both translation and secretion. Increases in amino acids and insulin after a meal activate the mammalian target of rapamycin (mTOR) pathway, leading to an increase in specific rates of leptin biosynthesis. Cross-talk among mTOR, PKA, and AMPactivated protein kinase pathways appears to integrate hormonal and nutrient signals that regulate leptin mRNA translation, at least in part through mechanisms involving its 5Ј-and 3Ј-untranslated regions. In addition, the rate of leptin secretion from preformed stores in response to hormonal cues is also regulated. Insulin stimulates, and adrenergic agonists inhibit, leptin secretion, and this likely contributes to variations in the magnitude of nutrition-related leptin excursions and oscillations. Overall, the study of leptin production has contributed to a deepening understanding of leptin biology and, more broadly, to our understanding of the cellular and molecular mechanisms by which the adipocyte integrates hormonal and nutrient signals to regulate adipokine production. adipose tissue; adrenergic; feeding; insulin; obesity LEPTIN IS A 16-KDA PROTEIN encoded by the obese (lep) gene that is expressed and secreted mainly by adipocytes. When energy stores are low, a fall in leptin decreases thermogenesis, promotes fatty acid (FA) over glucose oxidation, and decreases the activity of the hypothalamic pituitary adrenal and gonadal axes (1). Leptin also modulates the activities of the hematopoietic (5) and immune (52) systems, as well as angiogenesis (7).

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Section: Chronic Changes In Nutritional Status Regulate Leptin At Thementioning

confidence: 69%

Integration of hormonal and nutrient signals that regulate leptin synthesis and secretion

Lee¹,

Fried²

2009

American Journal of Physiology-Endocrinology and Metabolism

112

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“…29 Moreover, we have recently shown that a single (nearphysiological) dose of hydrocortisone (40 mg) signi®-cantly increases plasma leptin. 30 In conclusion, the natural glucocorticoid, hydrocortisone, increases leptin mRNA expression in human adipose tissue, and increases plasma leptin levels in healthy subjects. The metabolic signi®cance of the interaction between glucocorticoids and leptin remains to be elucidated.…”

Section: Discussionmentioning

confidence: 87%

Hormonal regulation of human leptin in vivo: effects of hydrocortisone and insulin

2000

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OBJECTIVE: To investigate the effects of continuous i.v. infusion of hydrocortisone or insulin on leptin secretion in humans. SUBJECTS: Six, nonfasting healthy adults (four women, two men), aged (mean AE s.e.m.) 36.6 AE 1.7 y; body mass index (BMI) 27.6 AE 0.9 kgam 2 . DESIGN: Randomized, placebo-controlled, cross-over study, with a 2-week`wash-out' period. INTERVENTIONS: Intravenous infusion of hydrocortisone (3.3 m mga(kg min)), insulin (1 mUa(kg min)) or normal saline (placebo) for 24 h. MEASUREMENTS: Blood sampling every 1 ± 2 h for measurement of glucose, insulin, cortisol and leptin; subcutaneous abdominal fat biopsy for determination of leptin mRNA expression. RESULTS: Plasma cortisol increased to 50.0 AE 0.4 m mgadl during hydrocortisone infusion, but was unaltered during saline or insulin infusion. The plasma insulin levels were: 28.5 AE 4.7 m mUaml (placebo), 40.8 AE 9.2 m mUaml (hydrocortisone, P 0.214), and 243 AE 23.0 m mUaml (insulin, P 0.0002). Peak hyperleptinemia occurred after 16 h of insulin and 20 h of hydrocortisone infusion; peakabaseline plasma leptin levels (ngaml) were 18.2 AE 4.2a15.1 AE 3.3 (placebo, P 0.056), 42.1 AE 7.0a16.0 AE 3.8 (hydrocortisone, 163%, P 0.008) and 30.2 AE 4.3a16.6 AE 2.7 (insulin, 83%, P 0.024). Adipocyte leptin mRNA increased by 350% after the hydrocortisone infusion. CONCLUSION: Hydrocortisone, a natural glucocorticoid, induces hyperleptinemia in vivo, with a potency greater than that of insulin. The interaction between glucocorticoids and leptin may be of metabolic signi®cance in humans.

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“…(Chavez et al, 1997;Warne, 2009) leptin? (Dagogo-Jack et al, 1997;Miell et al, 1996;Newcomer et al, 1998;Slieker et al, 1996;York, 1996) CRH and Ucn 3 (Bernier, 2006;Ohata and Shibasaki, 2011;Smagin et al, 1998) CART (Kask et al, 2000;Xu et al, 2010) Nesfatin-1 (Goebel et al, 2009;Stengel et al, 2011) NPW (Beck et al, 2010) Melanocortins (Liu et al, 2007;Yamano et al, 2004) central monoaminergic systems (Gibson, 2006) autonomous nervous system (Seematter et al, 2004) Stress induces hyperphagia due to reduction of: sensor specific satiety (Ahn and Phillips, 2012;Ortolani et al, 2011) stressor aversiveness (Piazza and Le Moal, 1997) CRH signaling? (Foster et al, 2009;la Fleur et al, 2005;Pecoraro et al, 2004) due to activation of central reward pathways (Piazza and Le Moal, 1997), due to alterations in gut microbiota (Tehrani et al, 2012) Glucocorticoids induce hyperphagia (Dallman, 1993;Drapeau et al, 2003;Epel et al, 2000;Tataranni et al, 1996) due to increased signaling of: NPY (Gyengesi et al, 2010;Krysiak et al, 1999;McKibbin et al, 1992;White et al, 1994;Wilding et al, 1993), AgRP (Coll et al, 2005;Savontaus et al, 2002), Nociceptin …”

Section: Q4mentioning

confidence: 99%

“…GCs can interact with leptin in the long-term regulation of energy intake and body adiposity. or leptin receptor deficiency is attenuated by ADX (York, 1996), supraphysiological doses of exogenous GCs increase leptin mRNA levels in ob/ob mice, leptin secretion in cultured rat adipocytes (Slieker et al, 1996), and circulating leptin concentrations in normal and obese humans (Dagogo-Jack et al, 1997;Miell et al, 1996;Newcomer et al, 1998). But these authors did not measure food intake, and it remains unknown whether GC-induced hyperleptinemia is followed by anorexia in humans.…”

Section: Central Anorexigenic Effectmentioning

confidence: 99%

Food-intake regulation during stress by the hypothalamo-pituitary-adrenal axis

Бажан¹,

Zelena²

2013

Brain Research Bulletin

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a b s t r a c tThe prevalence of obesity is increasing worldwide with serious consequences such as diabetes mellitus type 2 and cardiovascular diseases. Emotional stress is considered to be one of the main reasons of obesity development in humans. However, there are some contradictory results, which should be addressed. First of all stress induces anorexia, but not overeating in laboratory animals. Glucocorticoids, the effector molecules of the hypothalamo-pituitary-adrenocortical (HPA) axis stimulate and stress inhibits food intake. It is also not clear if stress is diabetogenic or an antidiabetogenic factor. The review will discusses these issues and the involvement of the whole HPA axis and its separate molecules (glucocorticoids, adrenocorticotropin, corticotropin-releasing hormone) in food intake regulation under stress.

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Dose-Dependent Cortisol-Induced Increases in Plasma Leptin Concentration in Healthy Humans

Cited by 120 publications

References 65 publications

Integration of hormonal and nutrient signals that regulate leptin synthesis and secretion

Integration of hormonal and nutrient signals that regulate leptin synthesis and secretion

Hormonal regulation of human leptin in vivo: effects of hydrocortisone and insulin

Food-intake regulation during stress by the hypothalamo-pituitary-adrenal axis

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