Food Intake-Induced Leptin Secretion Modulates Hypothalamo-Pituitary-Adrenal Axis Response and Hypothalamic Ob-Rb Expression to Insulin Administration

Giovambattista, Andrés; Chisari, Andrea N.; Gaillard, Rolf C.; Spinedi, Eduardo

doi:10.1159/000054603

Cited by 53 publications

(35 citation statements)

References 41 publications

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“…Ob-Rb expression in both testicular samples and purified Leydig cells was significantly (p < 0.05) lower in MSG than in CTR tissues. These results agree with the concept of homologous regulation of the expression of Ob-Rb in the rat hypothalamus [15], adrenal [38]and testis [7]shown by in vivo and in vitro experiments.…”

Section: Discussionsupporting

confidence: 91%

“…Effects of leptin on different endocrine target tissues, including the HPG axis are mediated by specific binding to the leptin receptor, which exhibits several splicing variants and several isoforms. Expression of the Ob-Rb receptor in different tissues is down-regulated by high circulating leptin levels [15, 38]. In the case of testis, leptin receptor isoforms are present [7], suggesting that leptin also exerts a direct endocrine action on the gonads.…”

Section: Discussionmentioning

confidence: 99%

“…Plasma leptin concentrations were determined by a radioimmunoassay (RIA) previously described in detail [15]. The detection range of the standard curve was 0.4–15 ng/ml.…”

Section: Methodsmentioning

confidence: 99%

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Modulatory Effects of Leptin on Leydig Cell Function of Normal and Hyperleptinemic Rats

et al. 2003

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Neonatal L-monosodium glutamate (MSG) administration in rats induces several neuroendocrine and metabolic disruptions. Leptin, the adipocyte product, modulates several neuroendocrine systems including the hypothalamic-pituitary-gonadal (HPG) axis in mammals. The aim of the present study was to determine whether MSG-induced chronic hyperleptinemia could play any relevant role in the hypogonadism developed by male rats when examined in adulthood. We found that 120-day-old MSG male rats displayed significant hyperleptinemia, hypogonadism, and undisturbed basic testis structure and spermatogenesis. In vitro studies in purified Leydig cells from normal (CTR) and MSG-damaged rats revealed that basal and human chorionic gonadotropin (hCG)-stimulated 17-hydroxy-progesterone (17-HO-P₄), Δ₄-androstenedione (Δ₄A) and testosterone (T) secretions were significantly lower in MSG than in CTR cells. Exposure to murine leptin (mleptin, 10^–8M) significantly inhibited hCG-elicited T secretion by CTR cells after 180 min incubation. While mleptin significantly inhibited hCG-stimulated Δ₄A output and the Δ₄A:17-OH-P₄ ratio of secretion, conversely, it failed to modify the ratio T:Δ₄A release by CTR Leydig cells. Interestingly, the effects of mleptin found on CTR Leydig cells were absent in MSG Leydig cells. Finally, endogenous hyperleptinemia was associated with a significant decrease in Leydig cell expression of Ob-Rb mRNA in MSG rats. In summary, this study demonstrates that: (1) mleptin inhibited testicular steroidogenesis in CTR rats; (2) MSG-treated rats showed lower in vitro 17-OH-P₄, Δ₄A and T production under basal and post-hCG stimulation conditions; (3) purified Leydig cells from MSG-treated rats displayed resistance to the inhibitory action of mleptin on T release, and (4) endogenous leptin exerts a modulatory effect on Leydig cell Ob-Rb mRNA expression. The inhibitory effect of leptin on testicular function is thus abrogated in MSG-damaged rats. The testicular leptin-resistance developed by MSG rats seems to be due to early chronic exposure of Leydig cells to high leptin circulating levels, which in turn down-regulate testicular Ob-Rb expression. It remains to be determined whether the testicular dysfunction of MSG rats can be reversed after correction of hyperleptinemia or whether it is an irreversible effect of the hypothalamic lesion.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Modulatory Effects of Leptin on Leydig Cell Function of Normal and Hyperleptinemic Rats

et al. 2003

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“…Diabetic rats that have low leptin levels also have an activated stress axis and leptin administration normalizes CS levels in these animals (Barber et al, 2003). More direct evidence comes from recent studies in which chronic leptin infusion was able to decrease circulating CS levels (Nowak et al, 2002) and increase in endogenous leptin levels by feeding could decrease the hypercorticosolemia produced by fasting (Giovambattista et al, 2000). However, the mechanisms by which leptin decreases CS levels or HPA function is unclear.…”

Section: Discussionmentioning

confidence: 99%

Systemic administration of leptin decreases plasma corticosterone levels: Role of hypothalamic norepinephrine

et al. 2008

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Leptin, an adipocyte-derived hormone, is known to regulate a variety of neuroendocrine functions. It inhibits the hypothalamo-pituitary-adrenal axis (HPA) in several animal models, however, the exact mechanism by which it does so is not known. Since norepinephrine (NE) is a key regulator of the HPA axis, we hypothesized that leptin could suppress HPA activity by decreasing NE levels. To study this, we implanted adult male Sprague Dawley rats with both a push-pull cannula in the paraventricular nucleus (PVN) and a catheter in the jugular vein. Animals were treated with either 0 or 100 μg or 500 μg of recombinant rat leptin (Lep). Push-pull perfusion was performed from 1000-1600 h. Perfusate samples were collected every 30 min and analyzed for NE levels using HPLC-EC. Blood samples were collected every 60 min and analyzed for coticosterone (CS) levels. To further understand the role of NE in this phenomenon animals were treated with either an α-1 adrenergic agonist, phenylephrine (PHE; 0.5 mg/KgBW), an α-2 adrenergic agonist, clonidine (CLON; 0.6 mg/ Kg BW), or a β adrenergic agonist, isoproterenol (ISO; 0.2 mg/Kg BW) alone or in combination with 500 μg of Lep. Pretreatment and hourly posttreatment blood samples were collected, plasma was separated and analyzed for CS levels. Leptin administration decreased NE release in the PVN significantly by 30 min (p<0.05). It also significantly reduced plasma CS levels at 240 and 300 min (p<0.05). Administration of either PHE or CLON in combination with leptin prevented the leptininduced decrease in CS. In contrast, administration of ISO along with leptin did not prevent the leptininduced decrease in CS. These results indicate that leptin decreases hypothalamic NE and plasma corticosterone and that this effect is most probably mediated through alpha-adrenergic receptors.

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“…50,65). Caloric deprivation results in rapid decreases of both ob mRNA and plasma leptin levels (3,13,30,35,40), and these changes are significantly and rapidly reversed within the first 1-6 h of refeeding (22,45,50,56). As discussed, NPY, AGRP, and POMC are downstream targets of leptin action; therefore, if an increase in circulating leptin during refeeding contributes to reversing the deprivation-induced changes in expression of these genes, the time course of reversal on refeeding should be subsequent to changes in circulating leptin levels.…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic NPY, AGRP, and POMC mRNA responses to leptin and refeeding in mice

Swart

Jahng

Overton

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

104

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Swart, I., J. W. Jahng, J. M. Overton, and T. A. Houpt. Hypothalamic NPY, AGRP, and POMC mRNA responses to leptin and refeeding in mice. Am J Physiol Regul Integr Comp Physiol 283: R1020-R1026, 2002 10.1152/ajpregu.00501.2001 increases hypothalamic neuropeptide Y (NPY) and agouti-related protein (AGRP) mRNA levels and decreases proopiomelanocortin (POMC) mRNA levels; refeeding restores these levels. We determined the time course of changes in hypothalamic NPY, AGRP, and POMC mRNA levels on refeeding after 24 h FD in C57BL mice by in situ hybridization. After 24 h deprivation, mice were refed with either chow or a palatable mash containing no calories or were injected with murine leptin (100 g) without food. Mice were perfused 2 or 6 h after treatment. Food deprivation increased hypothalamic NPY mRNA (108 Ϯ 6%) and AGRP mRNA (78 Ϯ 7%) and decreased hypothalamic POMC mRNA (Ϫ15 Ϯ 1%). Refeeding for 6 h, but not 2 h, was sufficient to reduce (but not restore) NPY mRNA, did not affect AGRP mRNA, and restored POMC mRNA levels to ad libitum control levels. Intake of the noncaloric mash had no effect on mRNA levels, and leptin administration after deprivation (at a dose sufficient to reduce refeeding in FD mice) was not sufficient to affect mRNA levels. These results suggest that gradual postabsorptive events subsequent to refeeding are required for the restoration of peptide mRNA to baseline levels after food deprivation in mice. palatable; preabsorptive; postabsorptive; time course; arcuate nucleus; in situ hybridization; neuropeptide Y; agoutirelated protein; proopiomelanocortin CALORIC DEPRIVATION INVOKES a complex array of hormonal, neural, and metabolic responses to reduce energy expenditure to defend body weight. Associated with reduced caloric availability is an increased drive to eat. Both the reduced energy expenditure and increased appetite associated with reduced energy availability may be regulated by a network of hypothalamic neuropeptides (30,52,61). Agouti-related protein (AGRP), a melanocortin receptor antagonist, is coexpressed with neuropeptide Y (NPY) in most hypothalamic NPYergic arcuate nucleus neurons (8), and hypothalamic peptide content and mRNA levels of both NPY (7, 21, 31) and AGRP (33, 42) are increased by food deprivation. Proopiomelanocortin (POMC) is expressed in a separate population of arcuate nucleus neurons and via ␣-melanocyte stimulating hormone (␣-MSH), a posttranslational product of POMC and a melanocortin receptor agonist, tonically inhibits food intake (5, 34), whereas food deprivation results in decreased POMC mRNA levels in the arcuate nucleus (42). Therefore, during conditions of altered energy balance, NPY and AGRP signaling via NPY-Y1/Y5 and melanocortin MC-4 receptors, respectively, and POMC/ ␣-MSH signaling also via MC-4 receptors are coordinately regulated to defend body weight and stimulate appetite, thus maintaining energy homeostasis.Little is known about the time course of the restoration of food deprivation-induced changes in hypothalamic peptide mRNA levels on ref...

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Food Intake-Induced Leptin Secretion Modulates Hypothalamo-Pituitary-Adrenal Axis Response and Hypothalamic Ob-Rb Expression to Insulin Administration

Cited by 53 publications

References 41 publications

Modulatory Effects of Leptin on Leydig Cell Function of Normal and Hyperleptinemic Rats

Modulatory Effects of Leptin on Leydig Cell Function of Normal and Hyperleptinemic Rats

Systemic administration of leptin decreases plasma corticosterone levels: Role of hypothalamic norepinephrine

Hypothalamic NPY, AGRP, and POMC mRNA responses to leptin and refeeding in mice

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