Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons

Furigo, Isadora C.; Teixeira, Pryscila D.S.; Souza, Gabriel Oliveira de; Couto, Gisele C. L.; Romero, Guadalupe García; Perelló, Mario; Frazão, Renata; Elias, Lucila Leico Kagohara; Metzger, Martin; List, Edward O.; Kopchick, John J.; Donato, José

doi:10.1038/s41467-019-08607-1

Cited by 74 publications

(147 citation statements)

References 46 publications

(63 reference statements)

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“…We found two-plex fluorescent ISH for GHRH or SST and tdTomato mRNAs colocalized in the ARC of GHR tdTom mice (Figure 3), as previously reported (12). In support of previous studies (19,31), we further confirmed a substantial overlap of GHR + neurons in the ARC with AgRP-expressing neurons in the GHR tdTom P mice (Supplementary Figure 3A). Additionally, in support of the single-cell sequencing data (31), we found a minimal colocalization with dopaminergic neurons (GHR tdTom+ /TH + cells), and with POMC neurons (GHR tdTom+ /β-endorphin + cells) in the ARC (Supplementary Figure 3B and 3C).…”

Section: Resultssupporting

confidence: 91%

“…We have recently shown that neuronal-specific deletion of GHR in leptin receptor (LepRb)-expressing neurons in the hypothalamus impaired hepatic glucose production and systemic lipid metabolism (18). Additionally, mice lacking GHR specifically in the orexigenic agouti-related peptide (AgRP) expressing neurons in the ARC display impaired responses to fasting and food restriction, while deletion of GHR from anorexigenic proopiomelanocortin (POMC) neurons in the ARC did not produce significant metabolic phenotype (19,20). Collectively, these results indicated unique roles of GHR-expressing neurons in the ARC in metabolic control.…”

Section: Introductionmentioning

confidence: 99%

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Growth hormone receptor (GHR)-expressing neurons in the hypothalamic arcuate nucleus regulate glucose metabolism and energy homeostasis

Lima

Debarba

Khan

et al. 2020

Preprint

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Growth hormone (GH) receptor (GHR), expressed in different brain regions, is known to participate in the regulation of whole-body energy homeostasis and glucose metabolism. However, GH activation of these GHR-expressing neurons is less studied. We have generated a novel GHR-driven Cre recombinase transgenic mouse line (GHR cre) in combination with the floxed tdTomato reporter mouse line we tracked and activated GHR-expressing neurons in different regions of the brain. We focused on neurons of the hypothalamic arcuate nucleus (ARC) where GHR was shown to elicit a negative feedback loop that regulates GH production. We found that ARC GHR+ neurons are co-localized with AgRP, GHRH, and somatostatin neurons, which were activated by GH stimulation. Using designer receptors exclusively activated by designer drugs (DREADDs) to control GHR-ARC neuronal activity, we revealed that activation of GHR-ARC neurons was sufficient in regulating distinct aspects of energy balance and glucose metabolism. Overall, our study provides a novel mouse model to study in vivo regulation and physiological function of GHR-expressing neurons in various brain regions. Furthermore, we identified for the first time specific neuronal population that responds to GH and directly linked it to metabolic responses in vivo.

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Section: Resultssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Growth hormone receptor (GHR)-expressing neurons in the hypothalamic arcuate nucleus regulate glucose metabolism and energy homeostasis

Lima

Debarba

Khan

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…B) Glucose utilization during a hyperinsulinemic-euglycemic clamp (P = 0.4274; n = 3-4). C ) Blood glucose levels during an ITT (n = [18][19][20][21][22]. D) AUC of the ITT (P = 0.6876).…”

Section: Discussionmentioning

confidence: 99%

Growth hormone enhances the recovery of hypoglycemia via ventromedial hypothalamic neurons

Furigo¹,

Souza²,

Teixeira³

et al. 2019

FASEB j.

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Growth hormone (GH) is secreted during hypoglycemia, and GH‐responsive neurons are found in brain areas containing glucose‐sensing neurons that regulate the counter‐regulatory response (CRR). However, whether GH modulates the CRR to hypoglycemia via specific neuronal populations is currently unknown. Mice carrying ablation of GH receptor (GHR) either in leptin receptor (LepR)‐ or steroidogenic factor‐1 (SF1)‐expressing cells were studied. We also investigated the importance of signal transducer and activator of transcription 5 (STAT5) signaling in SF1 cells for the CRR. GHR ablation in LepR cells led to impaired capacity to recover from insulin‐induced hypoglycemia and to a blunted CRR caused by 2‐deoxy‐d‐glucose (2DG) administration. GHR inactivation in SF1 cells, which include ventromedial hypothalamic neurons, also attenuated the CRR. The reduced CRR was prevented by parasympathetic blockers. Additionally, infusion of 2DG produced an abnormal hyperactivity of parasympathetic preganglionic neurons, whereas the 2DG‐induced activation of anterior bed nucleus of the stria terminalis neurons was reduced in mice without GHR in SF1 cells. Mice carrying ablation of Stat5a/b genes in SF1 cells showed no defects in the CRR. In summary, GHR expression in SF1 cells is required for a normal CRR, and these effects are largely independent of STAT5 pathway.—Furigo, I. C., de Souza, G. O., Teixeira, P. D. S., Guadagnini, D., Frazão, R., List, E. O., Kopchick, J. J., Prada, P. O., Donato, J., Jr. Growth hormone enhances the recovery of hypoglycemia via ventromedial hypothalamic neurons. FASEB J. 33, 11909–11924 (2019). http://www.fasebj.org

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“…Recent publications describe that in addition to its effects on the adipose tissue, GH also acts as a starvation signal that alerts the brain about energy deficiency, triggering adaptive responses to keep a minimum of energy deposits. This mechanism takes place at the central level by activating hypothalamic agouti-related protein neurons (AgRP) [87]. Figure 3 shows how GH acts in the adipocyte.…”

Section: Ghd and Adipose Tissuementioning

confidence: 99%

Growth Hormone Deficiency: Is It Just a Problem of Growth Impairment? Part II

Devesa¹

2020

Growth Disorders and Acromegaly

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As stated in the first part of this review, growth hormone (GH) acts on all organs and tissues, and untreated GH-deficient (GHD) patients suffer from several affectations occurring as a consequence of the lack of this key hormone. In the second part of this review, we will analyze the effects of GH on the liver, the kidney, the adrenal glands, the skeletal muscles, the bones, the hematopoietic system, the gastrointestinal system, and the adverse effects that may occur in these organs and systems in the GH deficiency not treated in children and adults. Apart from these, we conclude that GH is a co-hormone that seems to be necessary for the physiological actions of other important hormones in humans.

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Growth hormone regulates neuroendocrine responses to weight loss via AgRP neurons

Cited by 74 publications

References 46 publications

Growth hormone receptor (GHR)-expressing neurons in the hypothalamic arcuate nucleus regulate glucose metabolism and energy homeostasis

Growth hormone receptor (GHR)-expressing neurons in the hypothalamic arcuate nucleus regulate glucose metabolism and energy homeostasis

Growth hormone enhances the recovery of hypoglycemia via ventromedial hypothalamic neurons

Growth Hormone Deficiency: Is It Just a Problem of Growth Impairment? Part II

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