Towards Understanding the Direct and Indirect Actions of Growth Hormone in Controlling Hepatocyte Carbohydrate and Lipid Metabolism

Vázquez‐Borrego, Mari C.; Río-Moreno, Mercedes del; Kineman, Rhonda D

doi:10.3390/cells10102532

Cited by 26 publications

(20 citation statements)

References 218 publications

(286 reference statements)

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“…It is well established that a reduction of GH signaling is associated with liver steatosis and development of non-alcoholic steatohepatitis, both in humans and in mouse models, and increasing GH signaling can improve fatty liver endpoints (52,53). However, we found that treatment with a high dose of AAV8-STAT5 CA resulted in certain histopathological changes indicative of liver injury that cannot be attributed to the AAV8 infection per se , as they were not seen in AAV-Luciferase controls.…”

Section: Discussionmentioning

confidence: 99%

Constitutively active STAT5b feminizes mouse liver gene expression

Lau-Corona

Vergato

et al. 2022

Preprint

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STAT5 is an essential transcriptional regulator of the sex-biased actions of growth hormone (GH) in the liver. Delivery of constitutively active STAT5 (STAT5CA) to male mouse liver using an engineered adeno-associated virus with high tropism for the liver is shown to induce widespread feminization of the liver, with extensive induction of female-biased genes and repression of male-biased genes, largely mimicking results obtained when male mice are given GH as a continuous infusion. Many of the gene expression changes observed were associated with STAT5 binding to liver chromatin, supporting the proposed direct role of persistently active STAT5 in continuous GH-induced liver feminization. The feminizing effects of STAT5CA were dose-dependent; moreover, at higher levels, overexpression of STAT5CA resulted in some histopathology not seen in continuous GH-infused male liver, including hepatocyte hyperplasia and distorted liver architecture. These findings establish that the persistent activation of STAT5 by GH that characterizes female liver is by itself sufficient to account for the female-biased expression of a majority of female-biased genes. Moreover, histological changes seen when STAT5CA is overexpressed highlight the importance of carefully evaluating such effects before considering such STAT5 derivatives for therapeutic use in treating liver disease.

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Section: Discussionmentioning

confidence: 99%

Constitutively active STAT5b feminizes mouse liver gene expression

Lau-Corona

Vergato

et al. 2022

Preprint

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“…There is evidence showing that GH reduces the DNL of adipose tissue [ 154 ], leading to significant fat mass loss. In the context of nutrient deprivation such as fasting and Type I diabetes, circulating insulin and IGF1 levels are reduced [ 155 ], while the fasting-induced rise in GH promotes white adipose tissue (WAT) lipolysis [ 156 ]. Additionally, the promotion of GH is not through a STAT5-dependent mechanism.…”

Section: Growth Hormonesmentioning

confidence: 99%

“…For mice with specific knockout of STAT5 in adipocytes under chow-fed conditions, whose JAK-STAT signal pathway is dysregulated, increased adipose tissue mass will develop and improve body insulin sensitivity [ 159 ]. However, the loss of adipocyte STAT5 is neither associated with a reduction in WAT lipolysis nor does it impact the ability of GH treatment to reduce WAT mass [ 155 ]. These results suggested that WAT mass is affected by GH/GHR signaling in a STAT5-independent manner.…”

Section: Growth Hormonesmentioning

confidence: 99%

Important Hormones Regulating Lipid Metabolism

Zhang

Wei²,

Huang³

et al. 2022

Molecules

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There is a wide variety of kinds of lipids, and complex structures which determine the diversity and complexity of their functions. With the basic characteristic of water insolubility, lipid molecules are independent of the genetic information composed by genes to proteins, which determine the particularity of lipids in the human body, with water as the basic environment and genes to proteins as the genetic system. In this review, we have summarized the current landscape on hormone regulation of lipid metabolism. After the well-studied PI3K-AKT pathway, insulin affects fat synthesis by controlling the activity and production of various transcription factors. New mechanisms of thyroid hormone regulation are discussed, receptor α and β may mediate different procedures, the effect of thyroid hormone on mitochondria provides a new insight for hormones regulating lipid metabolism. Physiological concentration of adrenaline induces the expression of extrapituitary prolactin in adipose tissue macrophages, which promotes fat weight loss. Manipulation of hormonal action has the potential to offer a new therapeutic horizon for the global burden of obesity and its associated complications such as morbidity and mortality.

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“…The liver is a central metabolic organ, but also plays an important immunological role, serving to maintain tolerance under homeostatic conditions [ 1 , 2 , 3 ]. The liver is comprised of hepatocytes, which make up approximately two thirds of its total cell population and exert largely metabolic functions, comprising the synthesis of numerous types of plasma proteins—for example, albumin [ 4 ], fatty acids [ 5 ], carbohydrates [ 6 ], and bile acid metabolism [ 7 ]—but are also pivotal for detoxification [ 8 ]. The heterogeneous group of non-parenchymal cells (NPCs) plays an important role in immune regulation [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Enrichment Methods for Murine Liver Non-Parenchymal Cells Differentially Affect Their Immunophenotype and Responsiveness towards Stimulation

Medina‐Montano

Cacicedo

Svensson

et al. 2022

IJMS

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Hepatocytes comprise the majority of the liver and largely exert metabolic functions, whereas non-parenchymal cells (NPCs)—comprising Kupffer cells, dendritic cells and liver sinusoidal endothelial cells—control the immunological state within this organ. Here, we compared the suitability of two isolation methods for murine liver NPCs. Liver perfusion (LP) with collagenase/DNase I applied via the portal vein leads to efficient liver digestion, whereas the modified liver dissociation (LD) method combines mechanical dissociation of the retrieved organ with enzymatic degradation of the extracellular matrix. In cases of both LP and LD, NPCs were enriched by subsequent gradient density centrifugation. Our results indicate that LP and LD are largely comparable with regards to the yield, purity, and composition of liver NPCs. However, LD-enriched liver NPCs displayed a higher degree of activation after overnight cultivation, and accordingly were less responsive towards stimulation with toll-like receptor ligands that are frequently used as adjuvants, e.g., in nano-vaccines. We conclude that LP is more suitable for obtaining liver NPCs for subsequent in vitro studies, whereas LD as the less laborious method, is more convenient for parallel isolation of larger numbers of samples for ex vivo analysis.

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Towards Understanding the Direct and Indirect Actions of Growth Hormone in Controlling Hepatocyte Carbohydrate and Lipid Metabolism

Cited by 26 publications

References 218 publications

Constitutively active STAT5b feminizes mouse liver gene expression

Constitutively active STAT5b feminizes mouse liver gene expression

Important Hormones Regulating Lipid Metabolism

Enrichment Methods for Murine Liver Non-Parenchymal Cells Differentially Affect Their Immunophenotype and Responsiveness towards Stimulation

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