Tamas L Horvath

Tamas L Horvath
Yale University | YU · Section of Comparative Medicine

DVM, PhD

About

446
Publications
66,095
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
46,602
Citations
Citations since 2017
121 Research Items
20651 Citations
201720182019202020212022202301,0002,0003,0004,000
201720182019202020212022202301,0002,0003,0004,000
201720182019202020212022202301,0002,0003,0004,000
201720182019202020212022202301,0002,0003,0004,000
Introduction
Tamas L Horvath is the Jane and David W. Wallace Professor and Chair of the Department of Comparative Medicine, Yale University School of Medicine. Tamas does research in Physiology, Neuroscience and Endocrinology. Their most recent publication is 'Type I interferons instigate fetal demise after Zika virus infection.'

Publications

Publications (446)
Article
Full-text available
As marijuana use during adolescence has been increasing, the need to understand the effects of its long-term use becomes crucial. Previous research suggested that marijuana consumption during adolescence increases the risk of developing mental illnesses, such as schizophrenia, depression, and anxiety. Ghrelin is a peptide produced primarily in the...
Article
Aim The aim of this study was to examine the relationship between ghrelin levels and the subjective effects of alcohol in heavy drinkers, and to compare them to healthy controls. Methods Ghrelin levels were collected as part of two laboratory studies. Both groups received either IV infusion of saline or high dose of alcohol (100 mg%). In the study...
Article
Full-text available
The lateral septum (LS) has been implicated in the regulation of locomotion. Nevertheless, the neurons synchronizing LS activity with the brain’s clock in the suprachiasmatic nucleus (SCN) remain unknown. By interrogating the molecular, anatomical and physiological heterogeneity of dopamine neurons of the periventricular nucleus (PeVN; A14 catechol...
Article
Full-text available
The TET family of dioxygenases promote DNA demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Hypothalamic agouti-related peptide-expressing (AGRP-expressing) neurons play an essential role in driving feeding, while also modulating nonfeeding behaviors. Besides AGRP, these neurons produce neuropeptide Y (NPY) and the neu...
Article
The role of glia as active participants in brain functions has become increasingly evident. In this issue of Cell Metabolism, Herrera Moro Chao et al. reveal that astrocytes in the hypothalamic paraventricular nucleus (PVN) bidirectionally control neuronal behavior in response to metabolic cues and that this control is disrupted in obesity.
Article
Full-text available
Dysregulation of long interspersed nuclear element 1 (LINE-1, L1), a dominant class of transposable elements in the human genome, has been linked to neurodegenerative diseases, but whether elevated L1 expression is sufficient to cause neurodegeneration has not been directly tested. Here, we show that the cerebellar expression of L1 is significantly...
Article
Full-text available
The ventromedial hypothalamus (VMH) is known to regulate body weight and counterregulatory response. However, how VMH neurons regulate lipid metabolism and energy balance remains unknown. O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients...
Article
Full-text available
Hypothalamic agouti-related peptide and neuropeptide Y-expressing (AgRP) neurons have a critical role in both feeding and non-feeding behaviors of newborn, adolescent, and adult mice, suggesting their broad modulatory impact on brain functions. Here we show that constitutive impairment of AgRP neurons or their peripubertal chemogenetic inhibition r...
Article
Full-text available
Mitochondria in animals are associated with development, as well as physiological and pathological behaviors. Several conserved mitochondrial genes exist between plants and higher eukaryotes. Yet, the similarities in mitochondrial function between plant and animal species is poorly understood. Here, we show that FMT (FRIENDLY MITOCHONDRIA) from Ara...
Article
Full-text available
Phospholipid levels are influenced by peripheral metabolism. Within the central nervous system, synaptic phospholipids regulate glutamatergic transmission and cortical excitability. Whether changes in peripheral metabolism affect brain lipid levels and cortical excitability remains unknown. Here, we show that levels of lysophosphatidic acid (LPA) s...
Article
Significance The receptor tyrosine kinase Alk was originally discovered as an oncogenic fusion protein generated in anaplastic large cell lymphoma. A variety of oncogenic Alk fusion proteins were subsequently identified as key drivers of subsets of different cancers, including non-small cell lung cancer patients, large B cell lymphomas, and inflamm...
Article
Hypothalamic astrocytes play pivotal roles in both nutrient sensing and the modulation of synaptic plasticity of hypothalamic neuronal circuits in control of feeding and systemic glucose and energy metabolism. Here, we show the relevance of astrocytic fatty acid (FA) homeostasis under the opposing control of angiopoietin-like 4 (ANGPTL-4) and perox...
Conference Paper
Background: Loss of function mutations in gene encoding triggering receptor expressed on myeloid cells-2 (TREM2) have been strongly associated with the risk of developing Alzheimer's disease (AD) and other progressive dementias. In the brain, TREM2 is specifically expressed on microglia suggesting their active involvement in driving disease pathol...
Article
Full-text available
The hypocretin/orexin (Hcrt/Orx) system in the perifornical lateral hypothalamus has been recognized as a critical node in a complex network of neuronal systems controlling both physiology and behavior in vertebrates. Our understanding of the Hcrt/Orx system and its array of functions and actions have grown exponentially in merely two decades. This...
Article
Full-text available
Appropriate cristae remodeling is a determinant of mitochondrial function and bioenergetics and thus represents a crucial process for cellular metabolic adaptations. Here, we show that mitochondrial cristae architecture and expression of the master cristae-remodeling protein OPA1 in proopiomelanocortin (POMC) neurons, which are key metabolic sensor...
Article
Hepatic uptake and biosynthesis of fatty acids (FA), as well as the partitioning of FA into oxidative, storage, and secretory pathways are tightly regulated processes. Dysregulation of one or more of these processes can promote excess hepatic lipid accumulation, ultimately leading to systemic metabolic dysfunction. Angiopoietin-like-4 (ANGPTL4) is...
Article
Full-text available
Microglia have been implicated in synapse remodeling by phagocytosis of synaptic elements in the adult brain, but the mechanisms involved in the regulation of this process are ill-defined. By examining microglia-neuronal interaction in the ventral hippocampus, we found a significant reduction in spine synapse number during the light phase of the li...
Article
Full-text available
Increasing age is the strongest predictor of risk of COVID-19 severity and mortality. Immunometabolic switch from glycolysis to ketolysis protects against inflammatory damage and influenza infection in adults. To investigate how age compromises defense against coronavirus infection, and whether a pro-longevity ketogenic-diet (KD) impacts immune-sur...
Article
Background: Genetic mutations in triggering receptor expressed on myeloid cells-2 (TREM2) have been strongly associated with increased risk of developing Alzheimer’s disease (AD) and other progressive dementias. In the brain, TREM2 protein is specifically expressed on microglia suggesting their active involvement in driving disease pathology. Using...
Article
Full-text available
In the presence of high abundance of exogenous fatty acids, cells either store fatty acids in lipid droplets or oxidize them in mitochondria. In this study, we aimed to explore a novel and direct role of mitochondrial fission in lipid homeostasis in HeLa cells. We observed the association between mitochondrial morphology and lipid droplet accumulat...
Article
Full-text available
Pathologies of the micro- and macrovascular systems are a hallmark of the metabolic syndrome, which can lead to chronically elevated blood pressure. However, the underlying pathomechanisms involved still need to be clarified. Here, we report that an obesity-associated increase in serum leptin triggers the select expansion of the micro-angioarchitec...
Article
Synaptic plasticity is identified as innate to hypothalamic feeding circuits in their adaptation to the changing metabolic milieu in control of feeding and obesity. However, less is known about the regulatory principles of the dynamic changes of AgRP perikarya, a crucial region of the neuron gating excitation, and hence, feeding. Here we show that...
Article
Full-text available
Introduction: The etiology of sporadic Alzheimer's disease (AD) requires non-genetically modified animal models. Methods: The relationship of tau phosphorylation to calcium-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) dysregulation was analyzed in aging rhesus macaque dorsolateral prefrontal cortex (dlPFC) and rat primary cortica...
Article
Full-text available
Adiponectin is essential for the regulation of tissue substrate utilization and systemic insulin sensitivity. Clinical studies have suggested a positive association of circulating adiponectin with healthspan and lifespan. However, the direct effects of adiponectin on promoting healthspan and lifespan remain unexplored. Here, we are using an adipone...
Article
Full-text available
Mutations in KCNC3, which encodes the Kv3.3 potassium channel, cause degeneration of the cerebellum, but exactly how the activity of an ion channel is linked to the survival of cerebellar neurons is not understood. Here, we report that Kv3.3 channels bind and stimulate Tank Binding Kinase 1 (TBK1), an enzyme that controls trafficking of membrane pr...
Article
Full-text available
There are currently limited Food and Drug Administration (FDA)-approved drugs and vaccines for the treatment or prevention of Coronavirus Disease 2019 (COVID-19). Enhanced understanding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and pathogenesis is critical for the development of therapeutics. To provide insight into...
Article
Full-text available
The hypothalamic orexigenic Agouti-related peptide (AgRP)-expressing neurons are crucial for the regulation of whole-body energy homeostasis. Here, we show that fasting-induced AgRP neuronal activation is associated with dynamin-related peptide 1 (DRP1)-mediated mitochondrial fission and mitochondrial fatty acid utilization in AgRP neurons. In line...
Article
The development of the next generation therapy for Alzheimer’s disease (AD) presents a huge challenge given the number of promising treatment candidates that failed in trials, despite recent advancements in understanding of genetic, pathophysiologic and clinical characteristics of the disease. This review reflects some of the most current concepts...
Article
Full-text available
SARS-CoV-2 is the cause of a pandemic with growing global mortality. Using comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS), we identified 309 host proteins that bind the SARS-CoV-2 RNA during active infection. Integration of this data with ChIRP-MS data from three other RNA viruses defined viral specificity of R...
Article
Full-text available
A Correction to this paper has been published: https://doi.org/10.1038/s42255-021-00351-5.
Article
Full-text available
Objective The ventromedial nucleus of the hypothalamus (VMH) is a critical component of the forebrain pathways that regulate energy homeostasis. It also plays an important role in the metabolic response to fasting. However, the mechanisms contributing to these physiological processes remain elusive. Autophagy is an evolutionarily conserved mechanis...
Article
Since their discovery decades ago, the primary physiological and pathological effects of potassium channels have been attributed to their ion conductance, which sets membrane potential and repolarizes action potentials. For example, Kv3 family channels regulate neurotransmitter release by repolarizing action potentials. Here we report a surprising...
Article
Full-text available
Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus on the consequences of CNS infections. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain or...
Preprint
Microglia have been implicated in synapse remodeling by phagocytosis of synaptic elements in the adult brain. However, the underlying mechanism of such process is ill-defined. By examining microglia-neuronal interaction in the ventral hippocampus, we found a significant reduction in spine synapse number during the light phase of the light/dark cycl...
Preprint
Objective The ventromedial nucleus of the hypothalamus (VMH) is a critical component of the forebrain pathways that regulate energy homeostasis. It also plays an important role in the metabolic response to fasting. However, the mechanisms contributing to these physiological processes remain elusive. Autophagy is an evolutionarily conserved mechanis...
Article
Full-text available
Hypothalamic agouti-related peptide (AgRP) and neuropeptide Y-expressing neurons have a critical role in driving food intake, but also in modulating complex, non-feeding behaviours¹. We interrogated whether AgRP neurons are relevant to the emergence of anorexia nervosa symptomatology in a mouse model. Here we show, using in vivo fibre photometry, a...
Preprint
Full-text available
The bioenergetic function of mitochondrial fission is associated with uncoupled respiration or elimination of damaged mitochondria to maintain a healthy mitochondrial population. In the presence of a high abundance of exogenous fatty acids, cells can either store fatty acids in lipid droplets or oxidize them in mitochondria. Even though carnitine p...
Preprint
The hypothalamic orexigenic Agouti-related peptide (AgRP)-expressing neurons are crucial for the regulation of whole-body energy homeostasis. Here, we show that fasting-induced AgRP neuronal activation is associated with dynamin-related peptide 1 (Drp1)-mediated mitochondrial fission and mitochondrial fatty acid utilization in AgRP neurons. In line...
Preprint
Full-text available
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a pandemic with growing global mortality. There is an urgent need to understand the molecular pathways required for host infection and anti-viral immunity. Using comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS), we identified 309 host pr...
Preprint
Increasing age is the strongest predictor of risk of COVID-19 severity. Unregulated cytokine storm together with impaired immunometabolic response leads to highest mortality in elderly infected with SARS-CoV-2. To investigate how aging compromises defense against COVID-19, we developed a model of natural murine beta coronavirus (mCoV) infection wit...
Preprint
As marijuana use during adolescence has been increasing, the need to understand the effects of its long-term use becomes crucial. Previous research suggested that marijuana consumption during adolescence increases the risk of developing mental illness, such as schizophrenia, depression, and anxiety. Ghrelin is a peptide produced primarily in the gu...
Preprint
Mitochondria in animals are associated with development, as well as physiological and pathological behaviors. Several conserved mitochondrial genes exist between plants and higher eukaryotes. Yet, comparative mitochondrial function among plant and animal species is poorly understood. Here, we show that FMT (FRIENDLY MITOCHONDRIA) from Arabidopsis t...
Preprint
Full-text available
Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Reports indicate that 30-60% of patients with COVID-19 suffer from CNS symptoms. Yet, there is no consensus whether the virus can infect the brain, or what the consequences of infection are. Fo...
Article
Full-text available
Background: The effects of Covid-19 in pregnancy remain relatively unknown. We present a case of second trimester pregnancy with symptomatic Covid-19 complicated by severe preeclampsia and placental abruption. Methods: We analyzed placenta for the presence of SARS-CoV-2 through molecular and immunohistochemical assays and by and electron microsc...
Article
Full-text available
The brain has evolved in an environment where food sources are scarce and foraging for food is one of the major challenges for survival of the individual and species. Basic and clinical studies show that obesity/overnutrition leads to overwhelming changes in the brain in animals and humans. However, the exact mechanisms underlying the consequences...
Article
The mechanism by which maternal obesity influences fetal brain development and behavior is not well understood. In this issue of the JCI, Lippert et al. showed that feeding maternal mice a high-fat diet (HFD) during lactation attenuated the activity of dopamine (DA) midbrain neurons and altered the DA-related behavioral phenotype seen in the offspr...
Preprint
Full-text available
SARS-CoV-2, the causative agent of COVID-19, has resulted in more than 3,000,000 infections and 200,000 deaths. There are currently no approved drugs or vaccines for the treatment or prevention of COVID-19. Enhanced understanding of SARS-CoV-2 infection and pathogenesis is critical for the development of therapeutics. To reveal insight into viral r...
Preprint
Full-text available
Background: The effects of Covid-19 in pregnancy remain relatively unknown. We present a case of second trimester pregnancy with symptomatic Covid-19 complicated by severe preeclampsia and placental abruption. Methods: We analyzed placenta for the presence of SARS-CoV-2 through molecular and immunohistochemical assays and by and electron microscop...
Article
Full-text available
Astrocytes represent central regulators of brain glucose metabolism and neuronal function. They have recently been shown to adapt their function in response to alterations in nutritional state through responding to the energy state-sensing hormones leptin and insulin. Here, we demonstrate that glucagon-like peptide (GLP)-1 inhibits glucose uptake a...
Article
Full-text available
Homeostatic and hedonic pathways distinctly interact to control food intake. Dysregulations of circuitries controlling hedonic feeding may disrupt homeostatic mechanisms and lead to eating disorders. The anorexigenic peptides nucleobindin-2 (NUCB2)/nesfatin-1 may be involved in the interaction of these pathways. The endogenous levels of this peptid...
Preprint
Full-text available
The hypothalamus is the main regulatory center of many homeostatic processes, such as reproduction, food intake, and sleep-wake behavior. Recent findings show that there is a strongly interdependent side-linked localization of hypothalamic functions between the left and right hemispheres. The goal of the present study was to trace functional asymme...
Article
We hypothesized that bone evolved, in part, to enhance the ability of bony vertebrates to escape danger in the wild. In support of this notion, we show here that a bone-derived signal is necessary to develop an acute stress response (ASR). Indeed, exposure to various types of stressors in mice, rats (rodents), and humans leads to a rapid and select...
Article
Full-text available
Mitochondria are dynamic organelles that continually adapt their structure through fusion and fission in response to changes in their bioenergetic environment. Targeted deletion of mitochondrial fusion protein mitofusin1 (MFN1) in oocytes resulted in female infertility associated with failure to achieve oocyte maturation. Oocyte-granulosa cell comm...
Article
Full-text available
Current findings suggest that accumulation of amyloid-β (Aβ) and hyperphosphorylated tau in the brain disrupt synaptic function in hippocampal-cortical neuronal networks leading to impairment in cognitive and affective functions in Alzheimer's disease (AD). Development of new disease-modifying AD drugs are challenging due to the lack of predictive...
Article
Full-text available
Mitochondria change their shape through fusion and fission in order to adapt to their metabolic milieu. Mitofusin-2 (MFN2) is a key regulatory protein in this process, mediating mitochondrial fusion and interaction with endoplasmic reticulum. Targeted deletion of Mfn2 in oocytes resulted in mitochondrial dysfunction and female subfertility associat...
Article
The paraventricular hypothalamus (PVH) plays a pivotal role in regulating energy balance, though circuit mechanisms remain obscure. In this issue of Neuron, Li et al. (2019b) identify a circuit involving PVH PDYN neurons that, separately and synergistically with PVH MC4R neurons, controls feeding behaviors.
Article
Anorexia Nervosa (AN) is an eating disorder characterized by severe hypophagia, high levels of physical activity, harsh weight loss and an intense fear of weight gain. It has the highest mortality rate among psychiatric illnesses and, due to the unknown underlying neurobiology, it is challenging to treat. Agouti-related protein (AgRP) neurons, whic...
Article
Full-text available
We found that exposure of adult animals to calorie-dense foods rapidly abolished expression of mitofusin 2 (Mfn2), a gene promoting mitochondrial fusion and mitochondrion-endoplasmic reticulum interactions, in white and brown fat. Mfn2 mRN was also robustly lower in obese human subjects compared with lean controls. Adipocyte-specific knockdown of M...
Article
Mitochondria play a central role in the regulation of energy metabolism in oocytes and preimplantation embryos, where the number and morphology of mitochondria and mitochondrial DNA (mtDNA) content are tightly regulated. A number of mouse models with mitochondrial dysfunction result in infertility, further confirming the key role of mitochondria in...
Article
Astrocytes, microglia, and tanycytes play active roles in the regulation of hypothalamic feeding circuits. These non-neuronal cells are crucial in determining the functional interactions of specific neuronal subpopulations involved in the control of metabolism. Recent advances in biology, optics, genetics, and pharmacology have resulted in the emer...