1. Chronic hyperprolactinemia evoked by disruption of lactotrope dopamine D2 receptors impacts on liver and adipocyte genes related to glucose and insulin balance
- Author
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Catalina De Winne, Esteban Fiore, Felicitas Lopez-Vicchi, Guillermo Mazzolini, Marcelo Rubinstein, Belen Brie, Damasia Becu-Villalobos, Maria Ines Perez-Millan, Guillermina Maria Luque, and Ana Maria Ornstein
- Subjects
0301 basic medicine ,DOPAMIN ,Physiology ,Lactotrophs ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Gene Expression ,PROLACTIN ,GLUCOSE ,purl.org/becyt/ford/1 [https] ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Adipocyte ,Adipocytes ,Homeostasis ,Insulin ,Receptor ,Mice, Knockout ,Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ,Nuclear Proteins ,Bioquímica y Biología Molecular ,INSULIN ,Immunohistochemistry ,Up-Regulation ,Liver ,Lipogenesis ,Female ,Sterol Regulatory Element Binding Protein 1 ,CIENCIAS NATURALES Y EXACTAS ,medicine.medical_specialty ,Receptors, Prolactin ,Radioimmunoassay ,030209 endocrinology & metabolism ,Enzyme-Linked Immunosorbent Assay ,Biology ,Real-Time Polymerase Chain Reaction ,Prolactin cell ,Ciencias Biológicas ,03 medical and health sciences ,Physiology (medical) ,Dopamine receptor D2 ,Internal medicine ,medicine ,Animals ,Obesity ,purl.org/becyt/ford/1.6 [https] ,Glucokinase ,Receptors, Dopamine D2 ,Glucose Tolerance Test ,Fatty Liver ,Hyperprolactinemia ,030104 developmental biology ,Endocrinology ,Glucose ,chemistry ,Hepatocytes ,Transcription Factors - Abstract
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. Fil: Luque, Guillermina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: López Vicchi, María Felicitas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Ornstein, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Brie, Belen. Ministerio de Ciencia. Tecnología e Innovación Productiva. Agencia Nacional de Promoción Cientifíca y Tecnológica; Argentina Fil: De Winne, Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Fiore, Esteban Juan. Universidad Austral. Facultad de Cs.biomédicas. Instituto de Investigaciones En Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigaciones En Medicina Traslacional; Argentina Fil: Pérez Millán, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Mazzolini Rizzo, Guillermo Daniel. Universidad Austral. Facultad de Cs.biomédicas. Instituto de Investigaciones En Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigaciones En Medicina Traslacional; Argentina Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Becu, Damasia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
- Published
- 2016