Adiponectin and Resistin in the Neonatal Rat: Effects of Dexamethasone and Hypoxia

Raff, Hershel; Bruder, Eric D.

doi:10.1385/endo:29:2:341

Cited by 22 publications

(20 citation statements)

References 33 publications

(45 reference statements)

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“…For example, hydrocortisone treatment of both obese and normal rats was found to downregulate adiponectin mRNA expression in white adipose tissue, which was also reflected in plasma adiponectin concentrations (Shi et al, 2010). On the other hand, dexamethasone dosing of both normal and hypoxic rats increased plasma adiponectin and similar effects were found in humans (Raff and Bruder, 2006;Jang et al, 2008).…”

Section: Introductionmentioning

confidence: 84%

Mechanistic Modeling of the Effects of Glucocorticoids and Circadian Rhythms on Adipokine Expression

Sukumaran

Jusko²,

DuBois³

et al. 2011

J Pharmacol Exp Ther

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A mechanism-based model was developed to describe the effects of methylprednisolone (MPL), circadian rhythms, and the glucose/free fatty acid (FFA)/insulin system on leptin and adiponectin expression in white adipose tissue in rats. Fiftyfour normal Wistar rats received 50 mg/kg MPL intramuscularly and were sacrificed at various times. An additional set of 54 normal Wistar rats were sacrificed at 18 time points across the 24-h light/dark cycle and served as controls. Measurements included plasma MPL, glucocorticoid receptor (GR) mRNA, leptin mRNA, adiponectin mRNA, plasma leptin, adiponectin, glucose, FFA, and insulin. MPL pharmacokinetics was described by a two-compartment model with two absorption components. All measured plasma markers and mRNA expression exhibited circadian patterns except for adiponectin and were described by Fourier harmonic functions. MPL caused significant down-regulation in GR mRNA with the nadir occurring at 5 h. MPL disrupted the circadian patterns in plasma glucose and FFA by stimulating their production. Plasma glucose and FFA subsequently caused an increase in plasma insulin. Furthermore, MPL disrupted the circadian patterns in leptin mRNA expression by stimulating its production. This rise was closely followed by an increase in plasma leptin. Both leptin mRNA and plasma leptin peaked at 12 h after MPL and eventually returned back to their circadian baselines. MPL and insulin had opposing effects on adiponectin mRNA expression and plasma adiponectin, which resulted in biphasic pharmacodynamic profiles. This small systems model quantitatively describes, integrates, and provides additional insights into various factors controlling adipokine gene expression.

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Section: Introductionmentioning

confidence: 84%

Mechanistic Modeling of the Effects of Glucocorticoids and Circadian Rhythms on Adipokine Expression

Sukumaran

Jusko²,

DuBois³

et al. 2011

J Pharmacol Exp Ther

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“…Very few studies in the clinical literature have examined the effect of OSA or its treatment with nasal continuous positive airway pressure on cortisol levels, although one study suggested that OSA could elevate cortisol levels (41). Another study in neonatal rats has shown that administration of the glucocorticoid dexamethasone can produce a state of relative insulin resistance and mimic the metabolic responses seen with hypoxic exposure (42). Clearly, there is a need for future studies to investigate the relationship between glucocorticoids and potentially other counterregulatory hormones in mediating decreased insulin sensitivity in response to OSA or IH.…”

Section: Discussionmentioning

confidence: 99%

Intermittent Hypoxia Causes Insulin Resistance in Lean Mice Independent of Autonomic Activity

Iiyori

Alonso

et al. 2007

Am J Respir Crit Care Med

319

236

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Rationale and Objectives: Although many clinical physiology and epidemiology studies show an association between obstructive sleep apnea (OSA) and markers of insulin resistance, no causal pathway has been established. The purpose of the current study was to determine if the intermittent hypoxia (IH) stimulus that characterizes OSA causes insulin resistance in the absence of obesity. Furthermore, we assessed the impact of IH on specific metabolic function in liver and muscle. Finally, we examined the potential mechanistic role of the autonomic nervous system (ANS) in mediating insulin resistance in response to IH. Methods and Results: Hyperinsulinemic euglycemic clamps were conducted and whole-body insulin sensitivity, hepatic glucose output, and muscle-specific glucose utilization assessed in conscious, chronically instrumented adult male C57BL/6J mice exposed to (1 ) IH (achieving a nadir of FI O 2 ϭ 5-6% at 60 cycles/h for 9 h), (2 ) intermittent air as a control, (3 ) IH with ANS blockade (hexamethonium), or (4 ) IA with ANS blockade. IH decreased whole-body insulin sensitivity compared with intermittent air (38.8 Ϯ 2.7 vs. 49.4 Ϯ 1.5 mg/ kg/min, p Ͻ 0.005) and reduced glucose utilization in oxidative muscle fibers, but did not cause a change in hepatic glucose output. Furthermore, the reduction in whole-body insulin sensitivity during IH was not restored by ANS blockade. Conclusion: We conclude that IH can cause acute insulin resistance in otherwise lean, healthy animals, and that the response is associated with decreased glucose utilization of oxidative muscle fibers, but that it occurs independently of activation of the ANS.

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“…We have previously shown that chronic hypoxia in the neonatal rat elicits a multitude of physiological adaptations, including changes in intermediary metabolites and HPA axis function [7,13,15,16,18,20,26,36]. As part of a systematic approach to investigating these adaptations, we have also shown that the lipid composition of pup stomach contents (used as a surrogate for milk composition) was increased considerably during hypoxia [15,16].…”

Section: Discussionmentioning

confidence: 97%

“…Timed-pregnant Sprague-Dawley rats (Harlan Sprague Dawley, Indianapolis, IN; n = 36) were obtained at 14 days gestation and maintained on a standard diet and water ad libitum in a controlled environment (0600-1800 lights on). As soon as a litter was completely delivered, the dam and her pups were immediately moved to an environment chamber and exposed to 21% (normoxia group; n = 14) or 12% (hypoxia group; n = 13) O 2 as described previously [12,13,16,20,36]. Litter size was normalized to 12 pups per litter (mixed sexes).…”

Section: Animal Treatmentmentioning

confidence: 99%

“…Alterations in maternal food intake may have profound effects on the development of the neonate via changes in milk composition and/or production [4][5][6]. Systemic hypoxia modulates a number of physiological systems and has significant effects on food intake [7][8][9][10][11][12][13][14]. In addition, chronic hypoxia during lactation may affect the composition of expressed milk via alterations in maternal metabolism and mammary gland physiology [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

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Epidermal Growth Factor and Parathyroid Hormone-related Peptide mRNA in the Mammary Gland and their Concentrations in Milk: Effects of Postpartum Hypoxia in Lactating Rats

Bruder

Hoof

Young³

et al. 2008

Horm Metab Res

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The physiological adaptations of the neonatal rat to hypoxia from birth include changes in gastrointestinal function and intermediary metabolism. We hypothesized that the hypoxic lactating dam would exhibit alterations in mammary gland function leading to changes in the concentration of milk peptides that are important in neonatal gastrointestinal development. The present study assessed the effects of chronic hypoxia on peptides produced by the mammary glands and present in milk. Chronic hypoxia decreased the concentration of epidermal growth factor (EGF) in expressed milk and pup stomach contents and decreased maternal mammary gland Egf mRNA. The concentration of parathyroid hormone-related protein (PTHrp) was unchanged in milk and decreased in pup stomach contents; however, mammary Pthlh mRNA was increased by hypoxia. There was a significant increase in adiponectin concentrations in milk from hypoxic dams. Chronic hypoxia decreased maternal body weight, and pair feeding normoxic dams an amount of food equivalent to hypoxic dam food intake decreased body weight to an equivalent degree. Decreased food intake did not affect the expression of Egf, Pthlh, or Lep mRNA in mammary tissue. The results indicated that chronic hypoxia modulated mammary function independently of hypoxia-induced decreases in maternal food intake. Decreased EGF and increased adiponectin concentrations in milk from hypoxic dams likely affect the development of neonatal intestinal function.

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Adiponectin and Resistin in the Neonatal Rat: Effects of Dexamethasone and Hypoxia

Cited by 22 publications

References 33 publications

Mechanistic Modeling of the Effects of Glucocorticoids and Circadian Rhythms on Adipokine Expression

Mechanistic Modeling of the Effects of Glucocorticoids and Circadian Rhythms on Adipokine Expression

Intermittent Hypoxia Causes Insulin Resistance in Lean Mice Independent of Autonomic Activity

Epidermal Growth Factor and Parathyroid Hormone-related Peptide mRNA in the Mammary Gland and their Concentrations in Milk: Effects of Postpartum Hypoxia in Lactating Rats

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