Chronic hyperprolactinemia evoked by disruption of lactotrope dopamine d2 receptors impacts on liver and adipocyte genes related to glucose and insulin balance
We studied the impact of high prolactin titers on liver and adipocyte gene expression related to glucose and insulin homeostasis in correlation with obesity onset. To that end we used mutant female mice that selectively lack dopamine type 2 receptors (D2Rs) from pituitary lactotropes (lacDrd2KO), wh...
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2016
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01931849_v311_n6_pE974_Luque http://hdl.handle.net/20.500.12110/paper_01931849_v311_n6_pE974_Luque |
| Aporte de: |
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paper:paper_01931849_v311_n6_pE974_Luque |
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dspace |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Carbohydrate-responsive element-binding protein Glucokinase Insulin Lipogenesis Sterol regulatory element-binding protein-1c adiponectin carbohydrate responsive element binding protein cholesterol cre recombinase cyclophilin dopamine 2 receptor fatty acid synthase glucocorticoid receptor glucokinase glucose glucose 6 phosphate glycogen synthase 2 growth hormone receptor insulin lipoprotein lipase messenger RNA prolactin prolactin receptor protein sterol regulatory element binding protein 1c triacylglycerol triacylglycerol lipase unclassified drug dopamine 2 receptor glucose insulin Mlxipl protein, mouse nuclear protein prolactin receptor Srebf1 protein, mouse sterol regulatory element binding protein 1 transcription factor adipocyte adipose tissue animal experiment animal tissue Article body weight cholesterol blood level fatty liver female gene expression genotype glucose homeostasis glucose intolerance glycogen analysis glycogen liver level hyperprolactinemia hypophysis immunohistochemistry insulin response lipid storage liver liver cell liver weight mouse nonhuman obesity pancreas islet beta cell phenotype priority journal triacylglycerol blood level adipocyte animal enzyme linked immunosorbent assay genetics glucose tolerance test homeostasis hyperprolactinemia knockout mouse lipogenesis liver metabolism prolactin secreting cell radioimmunoassay real time polymerase chain reaction upregulation Adipocytes Animals Enzyme-Linked Immunosorbent Assay Fatty Liver Female Gene Expression Glucose Glucose Tolerance Test Hepatocytes Homeostasis Hyperprolactinemia Immunohistochemistry Insulin Lactotrophs Lipogenesis Liver Mice Mice, Knockout Nuclear Proteins Obesity Radioimmunoassay Real-Time Polymerase Chain Reaction Receptors, Dopamine D2 Receptors, Prolactin Sterol Regulatory Element Binding Protein 1 Transcription Factors Up-Regulation |
| spellingShingle |
Carbohydrate-responsive element-binding protein Glucokinase Insulin Lipogenesis Sterol regulatory element-binding protein-1c adiponectin carbohydrate responsive element binding protein cholesterol cre recombinase cyclophilin dopamine 2 receptor fatty acid synthase glucocorticoid receptor glucokinase glucose glucose 6 phosphate glycogen synthase 2 growth hormone receptor insulin lipoprotein lipase messenger RNA prolactin prolactin receptor protein sterol regulatory element binding protein 1c triacylglycerol triacylglycerol lipase unclassified drug dopamine 2 receptor glucose insulin Mlxipl protein, mouse nuclear protein prolactin receptor Srebf1 protein, mouse sterol regulatory element binding protein 1 transcription factor adipocyte adipose tissue animal experiment animal tissue Article body weight cholesterol blood level fatty liver female gene expression genotype glucose homeostasis glucose intolerance glycogen analysis glycogen liver level hyperprolactinemia hypophysis immunohistochemistry insulin response lipid storage liver liver cell liver weight mouse nonhuman obesity pancreas islet beta cell phenotype priority journal triacylglycerol blood level adipocyte animal enzyme linked immunosorbent assay genetics glucose tolerance test homeostasis hyperprolactinemia knockout mouse lipogenesis liver metabolism prolactin secreting cell radioimmunoassay real time polymerase chain reaction upregulation Adipocytes Animals Enzyme-Linked Immunosorbent Assay Fatty Liver Female Gene Expression Glucose Glucose Tolerance Test Hepatocytes Homeostasis Hyperprolactinemia Immunohistochemistry Insulin Lactotrophs Lipogenesis Liver Mice Mice, Knockout Nuclear Proteins Obesity Radioimmunoassay Real-Time Polymerase Chain Reaction Receptors, Dopamine D2 Receptors, Prolactin Sterol Regulatory Element Binding Protein 1 Transcription Factors Up-Regulation Pérez Millán, María Inés Rubinstein, Marcelo Chronic hyperprolactinemia evoked by disruption of lactotrope dopamine d2 receptors impacts on liver and adipocyte genes related to glucose and insulin balance |
| topic_facet |
Carbohydrate-responsive element-binding protein Glucokinase Insulin Lipogenesis Sterol regulatory element-binding protein-1c adiponectin carbohydrate responsive element binding protein cholesterol cre recombinase cyclophilin dopamine 2 receptor fatty acid synthase glucocorticoid receptor glucokinase glucose glucose 6 phosphate glycogen synthase 2 growth hormone receptor insulin lipoprotein lipase messenger RNA prolactin prolactin receptor protein sterol regulatory element binding protein 1c triacylglycerol triacylglycerol lipase unclassified drug dopamine 2 receptor glucose insulin Mlxipl protein, mouse nuclear protein prolactin receptor Srebf1 protein, mouse sterol regulatory element binding protein 1 transcription factor adipocyte adipose tissue animal experiment animal tissue Article body weight cholesterol blood level fatty liver female gene expression genotype glucose homeostasis glucose intolerance glycogen analysis glycogen liver level hyperprolactinemia hypophysis immunohistochemistry insulin response lipid storage liver liver cell liver weight mouse nonhuman obesity pancreas islet beta cell phenotype priority journal triacylglycerol blood level adipocyte animal enzyme linked immunosorbent assay genetics glucose tolerance test homeostasis hyperprolactinemia knockout mouse lipogenesis liver metabolism prolactin secreting cell radioimmunoassay real time polymerase chain reaction upregulation Adipocytes Animals Enzyme-Linked Immunosorbent Assay Fatty Liver Female Gene Expression Glucose Glucose Tolerance Test Hepatocytes Homeostasis Hyperprolactinemia Immunohistochemistry Insulin Lactotrophs Lipogenesis Liver Mice Mice, Knockout Nuclear Proteins Obesity Radioimmunoassay Real-Time Polymerase Chain Reaction Receptors, Dopamine D2 Receptors, Prolactin Sterol Regulatory Element Binding Protein 1 Transcription Factors Up-Regulation |
| description |
We studied the impact of high prolactin titers on liver and adipocyte gene expression related to glucose and insulin homeostasis in correlation with obesity onset. To that end we used mutant female mice that selectively lack dopamine type 2 receptors (D2Rs) from pituitary lactotropes (lacDrd2KO), which have chronic high prolactin levels associated with increased body weight, marked increments in fat depots, adipocyte size, and serum lipids, and a metabolic phenotype that intensifies with age. LacDrd2KO mice of two developmental ages, 5 and 10 mo, were used. In the first time point, obesity and increased body weight are marginal, although mice are hyperprolactinemic, whereas at 10 mo there is marked adiposity with a 136% increase in gonadal fat and a 36% increase in liver weight due to lipid accumulation. LacDrd2KO mice had glucose intolerance, hyperinsulinemia, and impaired insulin response to glucose already in the early stages of obesity, but changes in liver and adipose tissue transcription factors were time and tissue dependent. In chronic hyperprolactinemic mice liver Prlr were upregulated, there was liver steatosis, altered expression of the lipogenic transcription factor Chrebp, and blunted response of Srebp-1c to refeeding at 5 mo of age, whereas no effect was observed in the glycogenesis pathway. On the other hand, in adipose tissue a marked decrease in lipogenic transcription factor expression was observed when morbid obesity was already settled. These adaptive changes underscore the role of prolactin signaling in different tissues to promote energy storage. © 2016 the American Physiological Society. |
| author |
Pérez Millán, María Inés Rubinstein, Marcelo |
| author_facet |
Pérez Millán, María Inés Rubinstein, Marcelo |
| author_sort |
Pérez Millán, María Inés |
| title |
Chronic hyperprolactinemia evoked by disruption of lactotrope dopamine d2 receptors impacts on liver and adipocyte genes related to glucose and insulin balance |
| title_short |
Chronic hyperprolactinemia evoked by disruption of lactotrope dopamine d2 receptors impacts on liver and adipocyte genes related to glucose and insulin balance |
| title_full |
Chronic hyperprolactinemia evoked by disruption of lactotrope dopamine d2 receptors impacts on liver and adipocyte genes related to glucose and insulin balance |
| title_fullStr |
Chronic hyperprolactinemia evoked by disruption of lactotrope dopamine d2 receptors impacts on liver and adipocyte genes related to glucose and insulin balance |
| title_full_unstemmed |
Chronic hyperprolactinemia evoked by disruption of lactotrope dopamine d2 receptors impacts on liver and adipocyte genes related to glucose and insulin balance |
| title_sort |
chronic hyperprolactinemia evoked by disruption of lactotrope dopamine d2 receptors impacts on liver and adipocyte genes related to glucose and insulin balance |
| publishDate |
2016 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01931849_v311_n6_pE974_Luque http://hdl.handle.net/20.500.12110/paper_01931849_v311_n6_pE974_Luque |
| work_keys_str_mv |
AT perezmillanmariaines chronichyperprolactinemiaevokedbydisruptionoflactotropedopamined2receptorsimpactsonliverandadipocytegenesrelatedtoglucoseandinsulinbalance AT rubinsteinmarcelo chronichyperprolactinemiaevokedbydisruptionoflactotropedopamined2receptorsimpactsonliverandadipocytegenesrelatedtoglucoseandinsulinbalance |
| _version_ |
1768545781807054848 |
| spelling |
paper:paper_01931849_v311_n6_pE974_Luque2023-06-08T15:20:05Z Chronic hyperprolactinemia evoked by disruption of lactotrope dopamine d2 receptors impacts on liver and adipocyte genes related to glucose and insulin balance Pérez Millán, María Inés Rubinstein, Marcelo Carbohydrate-responsive element-binding protein Glucokinase Insulin Lipogenesis Sterol regulatory element-binding protein-1c adiponectin carbohydrate responsive element binding protein cholesterol cre recombinase cyclophilin dopamine 2 receptor fatty acid synthase glucocorticoid receptor glucokinase glucose glucose 6 phosphate glycogen synthase 2 growth hormone receptor insulin lipoprotein lipase messenger RNA prolactin prolactin receptor protein sterol regulatory element binding protein 1c triacylglycerol triacylglycerol lipase unclassified drug dopamine 2 receptor glucose insulin Mlxipl protein, mouse nuclear protein prolactin receptor Srebf1 protein, mouse sterol regulatory element binding protein 1 transcription factor adipocyte adipose tissue animal experiment animal tissue Article body weight cholesterol blood level fatty liver female gene expression genotype glucose homeostasis glucose intolerance glycogen analysis glycogen liver level hyperprolactinemia hypophysis immunohistochemistry insulin response lipid storage liver liver cell liver weight mouse nonhuman obesity pancreas islet beta cell phenotype priority journal triacylglycerol blood level adipocyte animal enzyme linked immunosorbent assay genetics glucose tolerance test homeostasis hyperprolactinemia knockout mouse lipogenesis liver metabolism prolactin secreting cell radioimmunoassay real time polymerase chain reaction upregulation Adipocytes Animals Enzyme-Linked Immunosorbent Assay Fatty Liver Female Gene Expression Glucose Glucose Tolerance Test Hepatocytes Homeostasis Hyperprolactinemia Immunohistochemistry Insulin Lactotrophs Lipogenesis Liver Mice Mice, Knockout Nuclear Proteins Obesity Radioimmunoassay Real-Time Polymerase Chain Reaction Receptors, Dopamine D2 Receptors, Prolactin Sterol Regulatory Element Binding Protein 1 Transcription Factors Up-Regulation We studied the impact of high prolactin titers on liver and adipocyte gene expression related to glucose and insulin homeostasis in correlation with obesity onset. To that end we used mutant female mice that selectively lack dopamine type 2 receptors (D2Rs) from pituitary lactotropes (lacDrd2KO), which have chronic high prolactin levels associated with increased body weight, marked increments in fat depots, adipocyte size, and serum lipids, and a metabolic phenotype that intensifies with age. LacDrd2KO mice of two developmental ages, 5 and 10 mo, were used. In the first time point, obesity and increased body weight are marginal, although mice are hyperprolactinemic, whereas at 10 mo there is marked adiposity with a 136% increase in gonadal fat and a 36% increase in liver weight due to lipid accumulation. LacDrd2KO mice had glucose intolerance, hyperinsulinemia, and impaired insulin response to glucose already in the early stages of obesity, but changes in liver and adipose tissue transcription factors were time and tissue dependent. In chronic hyperprolactinemic mice liver Prlr were upregulated, there was liver steatosis, altered expression of the lipogenic transcription factor Chrebp, and blunted response of Srebp-1c to refeeding at 5 mo of age, whereas no effect was observed in the glycogenesis pathway. On the other hand, in adipose tissue a marked decrease in lipogenic transcription factor expression was observed when morbid obesity was already settled. These adaptive changes underscore the role of prolactin signaling in different tissues to promote energy storage. © 2016 the American Physiological Society. Fil:Perez-Millan, M.I. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rubinstein, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01931849_v311_n6_pE974_Luque http://hdl.handle.net/20.500.12110/paper_01931849_v311_n6_pE974_Luque |