Insights from the clinical phenotype of subjects with Laron syndrome in Ecuador

Guevara‐Aguirre, Jaime; Bautista, Camila; Torres, Carlos Duarte; Peña, Gabriela; Guevara, Carolina; Palacios, Cristina; Guevara, Alexandra; Gavilanes, Antonio W. D.

doi:10.1007/s11154-020-09602-4

Cited by 15 publications

(14 citation statements)

References 85 publications

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“…To understand the metabolic functions of adipocyte STAT5, we generated mice lacking both Stat5 genes in adipocytes (STAT5 AKO ). Compared to littermate controls, STAT5 AKO mice fed chow diet had pronounced increased subcutaneous fat mass, similar to mammalian models with deficient GH signaling ( 3 – 7 ), and female STAT5 AKO mice had decreased insulin levels and improved insulin sensitivity as indicated by homeostasis model assessment of insulin resistance (HOMA-IR). Although both sexes of STAT5 AKO mice had increased adiposity, assessment of energy expenditure and whole adipose tissue gene expression revealed that loss of adipocyte STAT5 confers sexually dimorphic responses in mice.…”

Section: Introductionmentioning

confidence: 81%

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Loss of Adipocyte STAT5 Confers Increased Depot-Specific Adiposity in Male and Female Mice That Is Not Associated With Altered Adipose Tissue Lipolysis

et al. 2022

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STATs (Signal Transducers and Activators of Transcription) 5A and 5B are induced during adipocyte differentiation and are primarily activated by growth hormone (GH) and prolactin in fat cells. Previous studies in mice lacking adipocyte GH receptor or STAT5 support their roles in lipolysis-mediated reduction of adipose tissue mass. Male and female mice harboring adipocyte-specific deletion of both STAT5 genes (STAT5AKO) exhibit increased subcutaneous or inguinal adipose tissue mass, but no changes in visceral or gonadal fat mass. Both depots display substantial increases in adipocyte size with no changes in lipolysis in adipose tissue explants. RNA sequencing analysis of subcutaneous adipose tissue and indirect calorimetry experiments reveal sex-dependent differences in adipose gene expression and whole-body energy expenditure, respectively, resulting from the loss of adipocyte STAT5.

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Section: Introductionmentioning

confidence: 81%

“…However, some people with obesity are metabolically healthy ( 1 ), and subcutaneous fat can protect against metabolic dysfunction ( 2 ). Mouse models and humans with reduced growth hormone (GH) signaling exhibit increased subcutaneous adiposity but improved metabolic health ( 3 – 7 ).…”

Section: Introductionmentioning

confidence: 99%

Loss of Adipocyte STAT5 Confers Increased Depot-Specific Adiposity in Male and Female Mice That Is Not Associated With Altered Adipose Tissue Lipolysis

et al. 2022

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“…Despite their sparsity, unusual patients can inform cancer biology [20]. For example, families with rare and high penetrant germline mutations (Li-Fraumeni syndrome) have catalyzed understanding of the function of tumor suppressor genes [67], while populations with diminished cancer incidence (subjects with Laron syndrome in Ecuador) provided insights on cancer metabolism and the insulin-like growth factor (IGF) pathway in tumor progression [68]. In an analogous manner, cases with exceptionally prolonged survival may bear distinct molecular characteristics, the elucidation of which could ultimately improve the outcome of individuals with more typical disease trajectories [20].…”

Section: Discussionmentioning

confidence: 99%

In Silico Methods for the Identification of Diagnostic and Favorable Prognostic Markers in Acute Myeloid Leukemia

Yilmaz

Toy

Marquardt

et al. 2021

IJMS

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Acute myeloid leukemia (AML), the most common type of acute leukemia in adults, is mainly asymptomatic at early stages and progresses/recurs rapidly and frequently. These attributes necessitate the identification of biomarkers for timely diagnosis and accurate prognosis. In this study, differential gene expression analysis was performed on large-scale transcriptomics data of AML patients versus corresponding normal tissue. Weighted gene co-expression network analysis was conducted to construct networks of co-expressed genes, and detect gene modules. Finally, hub genes were identified from selected modules by applying network-based methods. This robust and integrative bioinformatics approach revealed a set of twenty-four genes, mainly related to cell cycle and immune response, the diagnostic significance of which was subsequently compared against two independent gene expression datasets. Furthermore, based on a recent notion suggesting that molecular characteristics of a few, unusual patients with exceptionally favorable survival can provide insights for improving the outcome of individuals with more typical disease trajectories, we defined groups of long-term survivors in AML patient cohorts and compared their transcriptomes versus the general population to infer favorable prognostic signatures. These findings could have potential applications in the clinical setting, in particular, in diagnosis and prognosis of AML.

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“…Decreased GH action takes two main clinical forms: GH deficiency (GHD), which has myriad causes, and Laron Syndrome (LS), which arises from GH receptor mutations ( Laron and Werner, 2021 ). While the symptoms of GH deficiency vary due to etiology ( Aguiar-Oliveira and Bartke, 2019 ), LS consistently causes short stature, improved glucose metabolism ( Guevara-Aguirre et al, 2021 ) with respect to family members without LS, as well as a reduction in diagnosed malignancies observed in the control group ( Guevara-Aguirre et al, 2011 ). Although GHD and LS may share many symptoms, their treatments differ.…”

Section: Introductionmentioning

confidence: 99%

Musculoskeletal Effects of Altered GH Action

et al. 2022

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Growth hormone (GH) is a peptide hormone that can signal directly through its receptor or indirectly through insulin-like growth factor 1 (IGF-1) stimulation. GH draws its name from its anabolic effects on muscle and bone but also has distinct metabolic effects in multiple tissues. In addition to its metabolic and musculoskeletal effects, GH is closely associated with aging, with levels declining as individuals age but GH action negatively correlating with lifespan. GH’s effects have been studied in human conditions of GH alteration, such as acromegaly and Laron syndrome, and GH therapies have been suggested to combat aging-related musculoskeletal diseases, in part, because of the decline in GH levels with advanced age. While clinical data are inconclusive, animal models have been indispensable in understanding the underlying molecular mechanisms of GH action. This review will provide a brief overview of the musculoskeletal effects of GH, focusing on clinical and animal models.

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Insights from the clinical phenotype of subjects with Laron syndrome in Ecuador

Cited by 15 publications

References 85 publications

Loss of Adipocyte STAT5 Confers Increased Depot-Specific Adiposity in Male and Female Mice That Is Not Associated With Altered Adipose Tissue Lipolysis

Loss of Adipocyte STAT5 Confers Increased Depot-Specific Adiposity in Male and Female Mice That Is Not Associated With Altered Adipose Tissue Lipolysis

In Silico Methods for the Identification of Diagnostic and Favorable Prognostic Markers in Acute Myeloid Leukemia

Musculoskeletal Effects of Altered GH Action

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