Growth hormone/STAT5 signaling in proopiomelanocortin neurons regulates glucoprivic hyperphagia

Quaresma, Paula G.F.; Teixeira, Pryscila D.S.; Furigo, Isadora C.; Wasinski, Frederick; Couto, Gisele C. L.; Frazão, Renata; List, Edward O.; Kopchick, John J.; Donato, José

doi:10.1016/j.mce.2019.110574

Cited by 27 publications

(41 citation statements)

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“…In the ARH, GH responsive cells are not restricted to AgRP/NPY neurons. In another study, we showed that approximately 60% of the neurons that express pro-opiomelanocortin (POMC) in the ARH express pSTAT5 after an injection of GH (54). GH action in POMC cells is not necessary for the regulation of energy or glucose homeostasis under basal conditions.…”

Section: Gh Action In the Cns Regulates Metabolismmentioning

confidence: 99%

“…GH action in POMC cells is not necessary for the regulation of energy or glucose homeostasis under basal conditions. However, the hyperphagia induced by a glucoprivic situation, caused by the administration of 2-deoxy-Dglucose (a drug that causes glucopenia and induces a robust counter-regulatory response), is significantly attenuated in mice lacking GHR in their POMC cells (Figure 3), indicating that GH action in POMC neurons regulates food intake in specific situations (54). GH is robustly secreted during hypoglycemia 7, and GH deficiency causes spontaneous hypoglycemia and impairs the counter-regulatory response to hypoglycemia (3,55).…”

Section: Gh Action In the Cns Regulates Metabolismmentioning

confidence: 99%

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Effects of growth hormone in the central nervous system

Wasinski

Frazão

Donato

2019

Archives of Endocrinology and Metabolism

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Growth hormone (GH) is best known for its effect stimulating tissue and somatic growth through the regulation of cell division, regeneration and proliferation. However, GH-responsive neurons are spread over the entire central nervous system, suggesting that they have important roles in the brain. The objective of the present review is to summarize and discuss the potential physiological importance of GH action in the central nervous system. We provide evidence that GH signaling in the brain regulates the physiology of numerous functions such as cognition, behavior, neuroendocrine changes and metabolism. Data obtained from experimental animal models have shown that disruptions in GH signaling in specific neuronal populations can affect the reproductive axis and impair food intake during glucoprivic conditions, neuroendocrine adaptions during food restriction, and counter-regulatory responses to hypoglycemia, and they can modify gestational metabolic adaptions. Therefore, the brain is an important target tissue of GH, and changes in GH action in the central nervous system can explain some dysfunctions presented by individuals with excessive or deficient GH secretion. Furthermore, GH acts in specific neuronal populations during situations of metabolic stress to promote appropriate physiological adjustments that restore homeostasis. Arch

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Section: Gh Action In the Cns Regulates Metabolismmentioning

confidence: 99%

Section: Gh Action In the Cns Regulates Metabolismmentioning

confidence: 99%

Effects of growth hormone in the central nervous system

Wasinski

Frazão

Donato

2019

Archives of Endocrinology and Metabolism

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“…First, we employed a lentivirus encoding a shRNA to selectively knockdown Tril in a non-cellspecific fashion in the arcuate nucleus (35). Second, we employed Cre-dependent adenoassociated viral vector to specifically inhibit Tril in POMC-expressing neurons (36). When either inhibition was performed in mice fed chow, there were virtually no changes in the phenotype, except for the increase in whole-body energy expenditure shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

POMC-specific knockdown of Tril reduces body adiposity and increases hypothalamic leptin responsiveness

Moura‐Assis

Nogueira

de-Lima-Júnior

et al. 2020

Preprint

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In a public dataset of transcripts differentially expressed in selected neuronal subpopulations of the arcuate nucleus, we identified TLR4-interactor with leucine-rich repeats (Tril) as a potential candidate for mediating the harmful effects of a high-fat diet in proopiomelanocortin (POMC) neurons. The non-cell-specific inhibition of Tril in the arcuate nucleus resulted in reduced hypothalamic inflammation, protection against diet-induced obesity associated with increased whole-body energy expenditure and increased systemic glucose tolerance. The inhibition of Tril, specifically in POMC neurons, resulted in a trend for protection against diet-induced obesity, increased energy expenditure and increased hypothalamic sensitivity to leptin. Thus, Tril emerges as a new component of the complex mechanisms that promote hypothalamic dysfunction in experimental diet-induced obesity.

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“…In order to study the effects of GH action in anorexigenic neurons which express the proopiomelanocortin (POMC) prohormone, POMC GHR KO mice ( 31 ) model was generated using the POMC Cre line. GH action in POMC neurons was not found to be required for maintenance of glucose homeostasis or energy regulation.…”

Section: Ghr Signaling In Brainmentioning

confidence: 99%

Tissue-Specific GHR Knockout Mice: An Updated Review

et al. 2020

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Growth hormone (GH) signaling plays a key role in mediating growth, development, metabolism, and lifespan regulation. However, the mechanisms of longevity regulation at the cellular and molecular level are still not well-understood. An important area in the field of GH research is in the development of advanced transgenic systems for conditional expression of GH signaling in a cell type- or tissue-specific manner. There have been many recent studies conducted to examine the effects of tissue-specific GHR disruption. This review updates our previous discussions on this topic and summarizes recent data on the newly-made tissue-specific GHR-KO mice including intestinal epithelial cells, bone, hematopoietic stem cells, cardiac myocytes, and specific brain regions. The data from these new genetically-engineered mice have a significant impact on our understanding of the local GH signaling function.

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Growth hormone/STAT5 signaling in proopiomelanocortin neurons regulates glucoprivic hyperphagia

Cited by 27 publications

References 50 publications

Effects of growth hormone in the central nervous system

Effects of growth hormone in the central nervous system

POMC-specific knockdown of Tril reduces body adiposity and increases hypothalamic leptin responsiveness

Tissue-Specific GHR Knockout Mice: An Updated Review

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