1. Analysis of Both Lipid Metabolism and Endocannabinoid Signaling Reveals a New Role for Hypothalamic Astrocytes in Maternal Caloric Restriction-Induced Perinatal Programming
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Julie A. Chowen, Jesús Aranda, Patricia Rivera, Lourdes Sánchez-Salido, Rubén Tovar, Antonio Vargas, Juan Suárez, Laura González-González, Fernando Rodríguez de Fonseca, [Tovar,R, Vargas,A, Aranda,J, Sánchez-Salido,L, González-González,L, Rodríguez de Fonseca,F, Suárez,J, Rivera,P] Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain. [Tovar,R, Rivera,P] UGC Salud Mental, Hospital Regional Universitario de Málaga, Málaga, Spain. [Tovar,R, Aranda,J] Andalucia Tech, Facultad de Medicina, Universidad de Málaga, Málaga, Spain. [Chowen,JA] Department of Endocrinology, Instituto de Investigación Biomédica la Princesa, Fundación Investigación Biomédica del Hospital Infantil Universitario Niño Jesús, Madrid, Spain. [Chowen,JA] CIBEROBN (Centro de Investigación Biomédica en Red Sobre Fisiopatología de la Obesidad y Nutrición), Instituto de Salud Carlos III, Madrid, Spain. [Chowen,JA] IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain. [Suárez,J] Departamento de Anatomía Humana, Medicina Legal e Historia de la Ciencia, Universidad de Málaga, Málaga, Spain., This research was funded by European Regional Development Funds-European Union (ERDF-EU) and Instituto de Salud Carlos III (ISCIII), grant numbers CP19/00068 and PI19/00343, and Consejería de Economía, Conocimien to y Universidad, Junta de Andalucía, grant number P18-TP 5194. J.S. (CPII17/00024) holds a 'Miguel Servet II' research contract from the National System of Health, EU-ERDF-ISCIII. P.R. (CP19/00068) holds a 'Miguel Servet I' research contract from the National System of Health, ISCIII (CD19/00068), co-funded by ESF ('Investing in your future').
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Astrocitos ,0301 basic medicine ,Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Newborn [Medical Subject Headings] ,Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation [Medical Subject Headings] ,Energy homeostasis ,Metabolismo de los lípidos ,0302 clinical medicine ,Phenomena and Processes::Metabolic Phenomena::Metabolism::Lipid Metabolism [Medical Subject Headings] ,Pregnancy ,lipid metabolism ,Organisms::Eukaryota::Animals [Medical Subject Headings] ,Atención perinatal ,Gliosis ,Biology (General) ,hypothalamus ,endocannabinoid system ,Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy [Medical Subject Headings] ,Spectroscopy ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Nutrition Therapy::Diet Therapy::Caloric Restriction [Medical Subject Headings] ,chemistry.chemical_classification ,Brain ,Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Signal Transduction [Medical Subject Headings] ,General Medicine ,Perinatal programming ,Endocannabinoid system ,Computer Science Applications ,Chemistry ,Endocannabinoides ,Hypothalamus ,Gestation ,Female ,Signal Transduction ,medicine.medical_specialty ,QH301-705.5 ,Offspring ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Size::Body Weight [Medical Subject Headings] ,Biology ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Chemicals and Drugs::Lipids::Fatty Acids::Endocannabinoids [Medical Subject Headings] ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Caloric Restriction ,Inflammation ,Body Weight ,Organic Chemistry ,Anatomy::Cells::Neuroglia::Astrocytes [Medical Subject Headings] ,astrocytes ,Caloric theory ,Lipid metabolism ,Anatomy::Nervous System::Central Nervous System::Brain [Medical Subject Headings] ,perinatal programming ,Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hypothalamus [Medical Subject Headings] ,Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger [Medical Subject Headings] ,Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Gliosis [Medical Subject Headings] ,Rats ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats [Medical Subject Headings] ,030104 developmental biology ,Enzyme ,Endocrinology ,Animals, Newborn ,Gene Expression Regulation ,Check Tags::Female [Medical Subject Headings] ,chemistry ,Astrocytes ,Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation [Medical Subject Headings] ,Hipotálamo ,030217 neurology & neurosurgery ,Endocannabinoids - Abstract
Maternal malnutrition in critical periods of development increases the risk of developing short- and long-term diseases in the offspring. The alterations induced by this nutritional programming in the hypothalamus of the offspring are of special relevance due to its role in energy homeostasis, especially in the endocannabinoid system (ECS), which is involved in metabolic functions. Since astrocytes are essential for neuronal energy efficiency and are implicated in brain endocannabinoid signaling, here we have used a rat model to investigate whether a moderate caloric restriction (R) spanning from two weeks prior to the start of gestation to its end induced changes in offspring hypothalamic (a) ECS, (b) lipid metabolism (LM) and/or (c) hypothalamic astrocytes. Monitorization was performed by analyzing both the gene and protein expression of proteins involved in LM and ECS signaling. Offspring born from caloric-restricted mothers presented hypothalamic alterations in both the main enzymes involved in LM and endocannabinoids synthesis/degradation. Furthermore, most of these changes were similar to those observed in hypothalamic offspring astrocytes in culture. In conclusion, a maternal low caloric intake altered LM and ECS in both the hypothalamus and its astrocytes, pointing to these glial cells as responsible for a large part of the alterations seen in the total hypothalamus and suggesting a high degree of involvement of astrocytes in nutritional programming.
- Published
- 2021