Regulation of corticotropin-releasing factor and urocortin 2/3 mRNA by leptin in hypothalamic N39 cells

Yamagata, Shinji; Kageyama, Kazunori; Akimoto, Kanako; Watanuki, Yutaka; Suda, Toshio; Daimon, Makoto

doi:10.1016/j.peptides.2013.09.010

Cited by 10 publications

(9 citation statements)

References 72 publications

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“…Leptin is involved in the regulation of corticotropin releasing factor (CRF). Some have reported that increases in leptin lead to increases in CRF [47,48]. Furthermore, elevated levels of CRF can increase anxiety-like behaviors in rodent models (See Ref.…”

Section: What May Be Driving Increases In Anxiety-like Behaviors?mentioning

confidence: 99%

Enhanced anxiety-like behavior emerges with weight gain in male and female obesity-susceptible rats

Alonso-Caraballo

Hodgson

Morgan

et al. 2019

Behavioural Brain Research

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Epidemiological data suggest that body mass index and obesity are strong risk factors for depression and anxiety. However, it is difficult to separate cause from effect, as predisposition to obesity may enhance susceptibility to anxiety, or vice versa. Here, we examined the effect of diet and obesity on anxiety-like behaviors in male and female selectively bred obesity-prone and obesity-resistant rats, and outbred Sprague-Dawley rats. We found that when obesity-prone and obesity-resistant rats do not differ in weight or fat mass, measures of anxiety-like behavior in the elevated plus maze and open field are similar between the two groups. However, once weight and fat mass diverge, group differences emerge, with greater anxiety in obesity-prone relative to obesity-resistant rats. This same pattern was observed for males and females. Interestingly, even when obesity-resistant rats were "forced" to gain fat mass comparable to obesity-prone rats (via prolonged access to 60% high-fat diet), anxiety-like behaviors did not differ from lean chow fed controls. In addition, a positive correlation between anxiety-like behaviors and adiposity were observed in male but not in female obesity-prone rats. Finally, diet-induced weight gain in and of itself was not sufficient to increase measures of anxiety in outbred male rats. Together, these data suggest that interactions between susceptibility to obesity and physiological alterations accompanying weight gain may contribute to the development of enhanced anxiety.

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Section: What May Be Driving Increases In Anxiety-like Behaviors?mentioning

confidence: 99%

Enhanced anxiety-like behavior emerges with weight gain in male and female obesity-susceptible rats

Alonso-Caraballo

Hodgson

Morgan

et al. 2019

Behavioural Brain Research

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“…Central treatment with leptin increases CRF mRNA expression in the PVN . On the other hand, the subcutaneous leptin osmotic minipump decreases CRF mRNA in the PVN of genetically obese ( ob/ob ) mice .…”

Section: Discussionmentioning

confidence: 98%

“…It has been proposed that CRF mediates the increase of energy expenditure through the activation of the sympathetic nervous system (35) and the inhibition of gastric emptying (8). Central treatment with leptin increases CRF mRNA expression in the PVN (36)(37)(38). On the other hand, the subcutaneous leptin osmotic minipump decreases CRF mRNA in the PVN of genetically obese (ob/ob) mice (39).…”

Section: Discussionmentioning

confidence: 99%

Oestradiol Modulates the Effects of Leptin on Energy Homeostasis by Corticotrophin‐Releasing Factor Type 2 Receptor

Marangon

Silva

Rorato

et al. 2014

J Neuroendocrinology

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In addition to its action in the control of the hypothalamic-pituitary-adrenal axis, corticotrophin-releasing factor (CRF) has been described as an anorexigenic neuropeptide, modulating food intake and energy expenditure. CRF synthesis is influenced by leptin, which would act to increase CRF neurone activation in the paraventricular nucleus (PVN). Gonadal hormones also participate in the regulation of energy homeostasis. The reduction of food intake and body weight gain in ovariectomised (OVX) rats treated with oestradiol is associated with an increase in CRF mRNA expression in the PVN. The present study aimed to investigate the role of CRF as a mediator of leptin responsiveness in the presence of oestradiol. Wistar female rats were bilaterally OVX and divided into three groups: OVX, OVX+E (i.e. treated with oestradiol) and OVX+PF (i.e. OVX pairfed with OVX+E). The rats received daily s.c. injections of either oestradiol cypionate or vehicle for 8 days. To evaluate the role of CRF on the effects of leptin, we performed an i.c.v. leptin injection (10 μg/5 μl) with or without previous i.c.v. treatment with an CRF-R2 antagonist. We observed that oestradiol replacement in OVX rats reduced body weight gain and food intake. The effects of exogenous leptin administration with respect to decreasing food intake and body weight, and increasing uncoupling protein-1 expression in the brown adipose tissue and neuronal activation in the arcuate nucleus, were reversed by previous administration of a CRF-R2 antagonist only in oestradiol-treated OVX rats. These effects appear to be mediated by CRF-2 receptor because the antagonist of this receptor reversed the action of oestradiol on the effects of leptin.

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“…Western blot analysis was conducted following the protocol described by Yamagata et al, with minor modifications. 22 Protein expression of phosphorylated STAT3/STAT3 in AtT20 cells was assessed by Western blot analysis. After being washed twice with phosphate-buffered saline, cells were lysed with Laemmli sample buffer and centrifuged to remove cell debris.…”

Section: Methodsmentioning

confidence: 99%

Inhibitory effects of a selective Jak2 inhibitor on adrenocorticotropic hormone production and proliferation of corticotroph tumor AtT20 cells

Asari

Kageyama

Nakada

et al. 2017

OTT

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PurposeThe primary cause of Cushing’s disease is adrenocorticotropic hormone (ACTH)-producing pituitary adenomas. EGFR signaling induces POMC mRNA-transcript levels and ACTH secretion from corticotroph tumors. The Jak–STAT pathway is located downstream of EGFR signaling; therefore, a Jak2 inhibitor could be an effective therapy for EGFR-related tumors. In this study, we determined the effect of a potent and selective Jak2 inhibitor, SD1029, on ACTH production and proliferation in mouse AtT20 corticotroph tumor cells.Materials and methodsAtT20 pituitary corticotroph tumor cells were cultured after transfection with PTTG1- or GADD45β-specific siRNA. Expression levels of mouse POMC, PTTG1, and GADD45β mRNAs were evaluated using quantitative real-time polymerase chain reaction. ACTH levels were measured using ACTH ELISA. Western blot analysis was performed to examine protein expression of phosphorylated STAT3/STAT3. Viable cells and DNA fragmentation were measured using a cell-proliferation assay and cell-death detection ELISA, respectively. Cellular DNA content was analyzed using fluorescence-activated cell sorting.ResultsSD1029 decreased POMC and PTTG1 mRNA and ACTH levels, while increasing GADD45β levels. The drug also decreased AtT20-cell proliferation and induced apoptosis, but did not alter cell-cycle progression. SD1029 also inhibited STAT3 phosphorylation. PTTG1 knockdown inhibited POMC mRNA levels and cell proliferation. However, combined treatment with PTTG1 knockdown and SD1029 had no additive effect on POMC mRNA levels or cell proliferation. GADD45β knockdown inhibited the SD1029-induced decrease in POMC mRNA levels and also partially inhibited the decrease in cell proliferation.ConclusionBoth PTTG1 and GADD45β may be responsible, at least in part, for the Jak2-induced suppression of ACTH synthesis and cell proliferation. Accordingly, therapies that target EGFR-dependent Jak2/STAT3 may have clinical applications for treating Cushing’s disease.

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Regulation of corticotropin-releasing factor and urocortin 2/3 mRNA by leptin in hypothalamic N39 cells

Cited by 10 publications

References 72 publications

Enhanced anxiety-like behavior emerges with weight gain in male and female obesity-susceptible rats

Enhanced anxiety-like behavior emerges with weight gain in male and female obesity-susceptible rats

Oestradiol Modulates the Effects of Leptin on Energy Homeostasis by Corticotrophin‐Releasing Factor Type 2 Receptor

Inhibitory effects of a selective Jak2 inhibitor on adrenocorticotropic hormone production and proliferation of corticotroph tumor AtT20 cells

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