Review
Neurosciences
Zhengchao Dou, Joe Eun Son, Chi-chung Hui
Summary: The hypothalamus, a highly conserved brain region, plays a crucial role in regulating physiological processes like energy balance. Neurons in the arcuate nucleus sense peripheral signals and regulate food intake and energy expenditure. Postnatal neurogenesis in the mouse hypothalamus, particularly in the first two postnatal weeks, contributes to remodeling and energy balance regulation. Radial glia-like cells, including RGL-NSCs, play a key role in this neurogenesis process, with genetic factors such as Irx3 and Irx5 influencing their properties. Understanding these mechanisms provides insights into hypothalamic remodeling and energy balance control.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Endocrinology & Metabolism
Joe Eun Son, Zhengchao Dou, Kyoung-Han Kim, Siyi Wanggou, Vincent Su Bin Cha, Rong Mo, Xiaoyun Zhang, Xinyu Chen, Troy Ketela, Xuejun Li, Xi Huang, Chi-chung Hui
Summary: Irx3 and Irx5 are involved in regulating hypothalamic postnatal neurogenesis and leptin response, with reduced gene dosage promoting neurogenesis and increasing the number of leptin-sensing arcuate neurons. Deletion of Irx3 in these cells also results in similar food intake and hypothalamic phenotype in mice.
Article
Biochemistry & Molecular Biology
Lanlan Jia, Zhengli Chen, Ting Pan, Yu Xia, Junbo He, Asad Jahangir, Xiaoli Wei, Wentao Liu, Riyi Shi, Chao Huang, Qihui Luo
Summary: The study shows that TRIM67 in the hypothalamus responds to body-energy homeostasis and a deficiency of TRIM67 exacerbates metabolic disorders in obese mice induced by high-fat diet. Neuroinflammation and apoptosis were found in the hypothalamus of obese TRIM67 KO mice. Reduced BDNF in the hypothalamus affects sympathetic nervous system innervation and contributes to lipid accumulation under high-fat diet exposure.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Zhiyin Zhang, Qihan Wu, Yang He, Peng Lu, Danjie Li, Minglan Yang, Weiqiong Gu, Ruixin Liu, Jie Hong, Jiqiu Wang
Summary: IRX3 gene is a functional downstream target of a common polymorphism in the FTO gene, and its overexpression can promote energy expenditure and brown/browning activities, resulting in reduced fat mass. Experimental studies in mice can verify the in vivo mechanism of IRX3 gene.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Multidisciplinary Sciences
Debora R. Sobreira, Amelia C. Joslin, Qi Zhang, Iain Williamson, Grace T. Hansen, Kathryn M. Farris, Noboru J. Sakabe, Nasa Sinnott-Armstrong, Grazyna Bozek, Sharon O. Jensen-Cody, Kyle H. Flippo, Carole Ober, Wendy A. Bickmore, Matthew Potthoff, Mengjie Chen, Melina Claussnitzer, Ivy Aneas, Marcelo A. Nobrega
Summary: This study identified a genomic region within the FTO gene that is strongly associated with obesity risk, where multiple variants on a common haplotype modify the regulatory properties of several enhancers targeting IRX3 and IRX5 from megabase distances. These enhancers affect gene expression in multiple tissues, including adipose and brain, and impart regulatory effects during a restricted temporal window. The findings suggest that disease-associated loci may involve extensive pleiotropy, allelic heterogeneity, shared allelic effects across tissues, and temporally restricted effects.
Article
Neurosciences
Celine Cansell, Katharina Stobbe, Clara Sanchez, Ophelia Le Thuc, Coralie-Anne Mosser, Selma Ben-Fradj, Joris Leredde, Cynthia Lebeaupin, Delphine Debayle, Lucile Fleuriot, Frederic Brau, Nadege Devaux, Alexandre Benani, Etienne Audinat, Nicolas Blondeau, Jean-Louis Nahon, Carole Rovere
Summary: Obesity in humans is associated with brain inflammation, glial reactivity, and immune cell infiltration. Studies in rodents have shown that glial reactivity occurs shortly after consuming a high-fat diet, even before obesity develops, primarily in the hypothalamus. This postprandial inflammation in the brain may contribute to the development of obesity and requires further characterization.
Article
Multidisciplinary Sciences
Joe Eun Son, Zhengchao Dou, Siyi Wanggou, Jade Chan, Rong Mo, Xuejun Li, Xi Huang, Kyoung-Han Kim, Jacques L. Michaud, Chi-chung Hui
Summary: The paraventricular nucleus of the hypothalamus (PVH) contains a cluster of Sim1-expressing neurons critical for feeding regulation. Sim1 haploinsufficiency results in hyperphagic obesity and disruption of PVH neurons. By studying the ectopic expression of Irx3 and Irx5 in Sim1(+) PVH cells, the research illustrates how misexpression of these genes contributes to the defects in Sim1 haploinsufficiency.
Review
Endocrinology & Metabolism
Christian L. Roth, Anna Zenno
Summary: Hypothalamic obesity is a complex and rare disorder that affects the regulation of energy intake and expenditure, often due to hypothalamic injury. Traditional obesity treatments have limited effectiveness in this condition, highlighting the need for advancements in pharmacotherapy.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Jiska van Schaik, Mila S. Welling, Corjan J. de Groot, Judith P. van Eck, Alicia Juriaans, Marcella Burghard, Sebastianus B. J. Oude Ophuis, Boudewijn Bakker, Wim J. E. Tissing, Antoinette Y. N. Schouten-van Meeteren, Erica L. T. van den Akker, Hanneke M. van Santen
Summary: This study retrospectively evaluated the treatment of children with HO with dextroamphetamine. The results showed that dextroamphetamine treatment can improve BMI, decrease hyperphagia, and improve energy level and behavior in some patients. However, some patients experienced side effects such as hypertension during treatment. Future studies are needed to further validate these findings.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Endocrinology & Metabolism
Andrew Folick, Suneil K. Koliwad, Martin Valdearcos
Summary: In mammals, myeloid cells help maintain the homeostasis of peripheral metabolic tissues and also serve as functional regulators within the mediobasal hypothalamus (MBH). Among them, microglia play important roles in brain physiology and pathology beyond their established roles as immune sentinels, influencing energy balance and potentially metabolic disease.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Neurosciences
Chong Song, Wei Wei, Tong Wang, Min Zhou, Yunshi Li, Bing Xiao, Dongyi Huang, Junwei Gu, Linyong Shi, Junjie Peng, Dianshi Jin
Summary: This study explored the mechanism of cognitive dysfunction in rats with hypothalamic obesity, finding that microglial infiltration and synapse loss mediated by the LHA in the hypothalamic-hippocampal circuit may be the underlying mechanism for memory impairments in these rats.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Engineering, Environmental
Qinlong Ma, Ping Deng, Min Lin, Lingling Yang, Le Li, Lu Guo, Lei Zhang, Mindi He, Yonghui Lu, Huifeng Pi, Yanwen Zhang, Zhengping Yu, Chunhai Chen, Zhou Zhou
Summary: BPA was identified as a risk factor for T2D in a case-control study, with long-term exposure exacerbating prediabetic symptoms induced by a high-fat diet. The effects included increased body mass, serum insulin levels, and impaired glucose tolerance in female mice, and impaired glucose tolerance in male mice. Hypothalamic inflammation mediated by TLR4 played a key role in the effects of BPA on prediabetes.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Xiaoning Wu, Elena Seraia, Stephanie B. Hatch, Xiao Wan, Daniel V. Ebner, Francesca Aroldi, Yanyan Jiang, Anderson J. Ryan, Thomas Bogenrieder, Ulrike Weyer-Czernilofsky, Guillaume Rieunier, Valentine M. Macaulay
Summary: Inhibition of both IGF and CHK1 leads to synergistic suppression of cell viability and tumor growth by downregulating RRM2 expression and reducing dNTP supply, resulting in delayed DNA replication and accumulation of unreplicated single-stranded DNA. This study highlights the therapeutic potential of targeting the IGF:CHK1 interaction and identifies RRM2 as a key target for synthetic lethality in cancer therapy.
Review
Biochemistry & Molecular Biology
Anup Bhusal, Md Habibur Rahman, Kyoungho Suk
Summary: The hypothalamus is a critical brain region for energy homeostasis regulation, with recent studies highlighting the role of glial cells in addition to neurons. However, inflammatory activation of these cells under metabolic stress conditions contributes to various metabolic diseases, worsening the disease state.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Endocrinology & Metabolism
Byong Seo Park, Dasol Kang, Kwang Kon Kim, Bora Jeong, Tae Hwan Lee, Jeong Woo Park, Shioko Kimura, Jung -Yong Yeh, Gu Seob Roh, Chang-Joong Lee, Sungchil Yang, Sunggu Yang, Jae Geun Kim, Byung Ju Lee
Summary: The study reveals that hypothalamic TTF-1 plays a crucial role in leptin signaling and activity, with its selective deletion enhancing the effects of leptin and alleviating obesity caused by leptin resistance. This suggests that TTF-1 may be a potential therapeutic target for the treatment of obesity.
MOLECULAR METABOLISM
(2022)
Article
Biochemical Research Methods
Tais M. Moinho, Mariana R. Tavares, Ana M. P. Campos, Renata Frazao, Martin Metzger, Jose Donato
Summary: A simple and low-cost method was developed to induce denaturation of constitutively expressed fluorescent proteins in brain slices of reporter animals. This method allows for the reuse of brain tissues without interfering with subsequent fluorescent staining experiments.
JOURNAL OF NEUROSCIENCE METHODS
(2022)
Article
Neurosciences
Pedro A. S. Nogueira, Alexandre Moura-Assis, Daniela S. Razolli, Bruna Bombassaro, Ariane M. Zanesco, Joana M. Gaspar, Jose Donato Junior, Licio A. Velloso
Summary: It was found that orphan GPCR expressed in the hypothalamus, with GPR68 playing a key role in metabolic regulation and influencing feeding control.
NEUROSCIENCE LETTERS
(2022)
Article
Anatomy & Morphology
Rudieri Souza, Debora Bueno, Leandro B. Lima, Maria J. Muchon, Luciano Goncalves, Jose Donato, Sara J. Shammah-Lagnado, Martin Metzger
Summary: This study compares the cortical inputs to the ventral tegmental area (VTA), laterodorsal tegmental nucleus (LDTg), and median raphe nucleus (MnR) in rats, revealing a similar set of prefrontal afferents. These findings further support the important role of the prefrontal cortex in controlling major state-setting mesopontine modulatory transmitter systems.
BRAIN STRUCTURE & FUNCTION
(2022)
Article
Endocrinology & Metabolism
Rodrigo S. Gaspar, Jeany Delafiori, Giuliana Zuccoli, Victor Corasolla Carregari, Thais P. Prado, Joseane Morari, Davi Sidarta-Oliveira, Carina S. Solon, Rodrigo R. Catharino, Eliana P. Araujo, Daniel Martins-de-Souza, Licio A. Velloso
Summary: Obesity is a major noncommunicable disease and its prevalence continues to increase globally. A recent study suggests that succinate, a tricarboxylic acid intermediate, can increase energy expenditure and potentially be used to treat obesity. The study found that exogenous succinate affects brown adipose tissue protein expression and when combined with liraglutide, promotes greater body mass reduction.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Jessica Catharine Gomes Duarte, Jozelia Gomes Pacheco Ferreira, Jose Donato Jr, Arpad Dobolyi, Jackson Cioni Bittencourt
Summary: The study aims to investigate the changes in amylin immunoreactivity during lactation, the modulation of amylin-ir neurons by litter size, and the colocalization of amylin-ir and MCH-ir neurons. The results show an increase in the number of amylin-ir neurons during lactation, reaching a peak at postpartum day 19 and decreasing significantly after weaning. There is no correlation between litter size and amylin-ir neuron numbers, and minimal overlap between amylin-ir and MCH-ir neurons.
JOURNAL OF CHEMICAL NEUROANATOMY
(2023)
Article
Neurosciences
Pedro A. S. Nogueira, Alexandre Moura-Assis, Ariane M. Zanesco, Bruna Bombassaro, Ana L. Gallo-Ferraz, Marcela R. Simoes, Daiane F. Engel, Daniela S. Razolli, Joana M. Gaspar, Jose Donato Junior, Licio A. Velloso
Summary: This study confirmed the expression of GPR139 in specific areas of the hypothalamus and its involvement in the regulation of energy balance and metabolism. Inhibiting the expression of hypothalamic GPR139 led to increased body mass, reduced fasting blood glucose levels, and increased insulin levels in mice. This effect may be mediated through the orexin system, as inhibition of GPR139 was accompanied by a reduction in orexin expression.
NEUROSCIENCE LETTERS
(2023)
Review
Endocrinology & Metabolism
Andrea Glezer, Mariana Ramos Santana, Marcello D. D. Bronstein, Jose Donato Jr, Raquel Soares Jallad
Summary: Hyperprolactinemia may increase the risk of cardiovascular diseases, but treatment with dopamine agonists could potentially improve this risk. Further studies are needed to better understand the association between hyperprolactinemia and cardiovascular disease risk.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Maria E. de Sousa, Daniela O. Gusmao, Willian O. dos Santos, Henrique T. Moriya, Felipe F. de Lima, Edward O. List, John J. Kopchick, Jose Donato Jr
Summary: GH receptor is expressed in the arcuate nucleus of the hypothalamus and modulates GH secretion. Short-term fasting and prolonged food restriction have different effects on the pattern of GH secretion, independent of GHR signaling in ARH(AgRP/NPY) neurons.
JOURNAL OF NEUROENDOCRINOLOGY
(2023)
Article
Cell Biology
Caroline A. Lino, Tabatha de Oliveira-Silva, Guilherme Lunardon, Camila Balbino-Silva, Vanessa M. Lima, Zhan-Peng Huang, Jose Donato, Ana Paula C. Takano, Maria Luiza Barreto-Chaves, Da-Zhi Wang, Gabriela P. Diniz
Summary: A high-fat diet can lead to obesity-related metabolic disorders by activating cellular senescence in white adipose tissue. Recent studies have shown that miR-22 plays a role in metabolic disorders and cellular senescence. It has been found that miR-22 deletion can attenuate obesity-related metabolic abnormalities. However, the role of miR-22 in HFD-induced cellular senescence in white adipose tissue is still unknown.
MECHANISMS OF AGEING AND DEVELOPMENT
(2023)
Article
Neurosciences
Frederick Wasinski, Mariana R. Tavares, Daniela O. Gusmao, Edward O. List, John J. Kopchick, Guilherme A. Alves, Renata Frazao, Jose Donato Jr
Summary: The present study aimed to investigate the effects of central growth hormone (GH) action on glial function in male mice. It was found that the expression of several neuroglial markers in the hypothalamus was decreased in dwarf GH- and insulin-like growth factor-1 (IGF-1)-deficient mice, while transgenic overexpression of GH led to increased expression of these markers. Moreover, hepatocyte-specific GH receptor knockout mice showed increased expression of glial markers, independent of IGF-1 secretion, while brain-specific GH receptor knockout mice showed reduced expression of these markers. These findings suggest that GHR signaling directly modulates the mRNA levels of neuroglial markers associated with inflammation.
NEUROSCIENCE LETTERS
(2023)
Article
Clinical Neurology
Mayara M. Andrade, Caroline Fernandes, Leticia Forny-Germano, Rafaella A. Goncalves, Michelle Gomes, Emily Castro-Fonseca, Angela M. Ramos-Lobo, Fernanda Tovar-Moll, Carlos Humberto Andrade-Moraes, Jose Donato Jr, Fernanda G. De Felice
Summary: This study identifies neuronal loss in the hippocampus and frontal cortex of two mouse models of obesity (Lep(ob/ob) and LepR(Null/Null)) using the isotropic fractionator. LepR(Null/Null) displayed increased non-neuronal cells, primarily glial cells, in the hippocampus, frontal cortex and hypothalamus. Quantitative measures showed that LepR(Null/Null) exhibits aggravated neurodegeneration when compared to Lep(ob/ob).
BRAIN COMMUNICATIONS
(2023)
Article
Endocrinology & Metabolism
Franco Barrile, Daniela Cassano, Gimena Fernandez, Pablo N. De Francesco, Mirta Reynaldo, Sonia Cantel, Jean-Alain Fehrentz, Jose Donato Jr, Helgi B. Schioth, Jeffrey M. Zigman, Mario Perello
Summary: This study found that ghrelin receptor (GHSR) is widely distributed in the mouse lateral hypothalamic area (LHA), mediating the effects of ghrelin on food intake. Local injections of ghrelin in LHA increase food intake and locomotor activity through the indirect recruitment of orexin neurons in LHA and activation of neurons in the arcuate nucleus (ARH). These findings provide a neuroanatomical and functional characterization of LHA GHSR neurons and their important role in regulating food intake.
PSYCHONEUROENDOCRINOLOGY
(2023)
Article
Cell Biology
Gabriel O. de Souza, Pryscila D. S. Teixeira, Niels O. S. Camara, Jose Donato
Summary: Hypothalamic mTORC1 signaling plays a crucial role in nutrient sensing. AgRP neurons integrate interoceptive and exteroceptive signals to regulate food intake, energy expenditure, and metabolic responses. The study found that mTORC1 signaling in AgRP neurons is not essential for regulating energy and glucose homeostasis but has an effect on some metabolic and neuroendocrine responses during food restriction and refeeding.
Article
Biochemistry & Molecular Biology
Thiago Rentz, Gabriel G. Dorighello, Renata R. dos Santos, Lohanna M. Barreto, Israelle N. Freitas, Carolina M. Lazaro, Daniela S. Razolli, Patricia M. Cazita, Helena C. F. Oliveira
Summary: CETP activity decreases HDL-cholesterol concentrations, but CETP expression in macrophages can reduce cholesterol accumulation, inflammation, and increase antioxidant capacity. Transplantation experiments showed that CETP expression did not change vascular lesion areas but decreased macrophage and neutrophil content, mitigating inflammation. These findings help explain the failure of CETP inhibitors in reducing atherosclerotic events.
Article
Endocrinology & Metabolism
Naira da Silva Mansano, Henrique Rodrigues Vieira, Roberta Araujo-Lopes, Raphael Escorsim Szawka, Jose Donato Jr, Renata Frazao
Summary: This study found that acute fasting can modulate the activity of the HPG axis and has gender-specific effects on Kisspeptin neurons. In female mice, fasting reduces the levels of luteinizing hormone and prolactin, while increasing follicle-stimulating hormone levels. Fasting also reduces Kisspeptin gene expression. Additionally, GABAergic transmission and the effects of neuropeptide Y on ARHKisspeptin neurons show gender differences.