Tamas L Horvath

Bio: Tamas L Horvath is an academic researcher from Max Planck Society. The author has contributed to research in topics: Dopaminergic & G protein-coupled inwardly-rectifying potassium channel. The author has an hindex of 1, co-authored 5 publications receiving 330 citations.

The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry

Abstract: Dopaminergic (DA) signaling governs the control of complex behaviors, and its deregulation has been implicated in a wide range of diseases. Here we demonstrate that inactivation of the Fto gene, encoding a nucleic acid demethylase, impairs dopamine receptor type 2 (D2R) and type 3 (D3R) (collectively, 'D2-like receptor')-dependent control of neuronal activity and behavioral responses. Conventional and DA neuron-specific Fto knockout mice show attenuated activation of G protein-coupled inwardly-rectifying potassium (GIRK) channel conductance by cocaine and quinpirole. Impaired D2-like receptor-mediated autoinhibition results in attenuated quinpirole-mediated reduction of locomotion and an enhanced sensitivity to the locomotor- and reward-stimulatory actions of cocaine. Analysis of global N(6)-methyladenosine (m(6)A) modification of mRNAs using methylated RNA immunoprecipitation coupled with next-generation sequencing in the midbrain and striatum of Fto-deficient mice revealed increased adenosine methylation in a subset of mRNAs important for neuronal signaling, including many in the DA signaling pathway. Several proteins encoded by these mRNAs had altered expression levels. Collectively, FTO regulates the demethylation of specific mRNAs in vivo, and this activity relates to the control of DA transmission.

thrifty phenotype: effect of gender glycerol-3-phosphate dehydrogenase gene exhibit a Mice with deletion of the mitochondrial

Abstract: [PDF] [Full Text] [Abstract] , March 1, 2005; 13 (3): 381-490. Obesity E. E. Snyder and C. Bouchard L. Perusse, T. Rankinen, A. Zuberi, Y. C. Chagnon, S. J. Weisnagel, G. Argyropoulos, B. Walts, The Human Obesity Gene Map: The 2004 Update [PDF] [Full Text] [Abstract] , April 1, 2006; 86 (2): 435-464. Physiol Rev J. E. Silva Thermogenic Mechanisms and Their Hormonal Regulation [PDF] [Full Text] [Abstract] , April 1, 2006; 14 (4): 529-644. Obesity and C. Bouchard T. Rankinen, A. Zuberi, Y. C. Chagnon, S. J. Weisnagel, G. Argyropoulos, B. Walts, L. Perusse The Human Obesity Gene Map: The 2005 Update [PDF] [Full Text] [Abstract] , July 3, 2006; 116 (7): 1886-1901. J. Clin. Invest. Fekete, A. Suzuki, T. W. Mak, W. Krone, T. L. Horvath, F. M. Ashcroft and J. C. Bruning Burdakov, E. Rother, R. Janoschek, J. Alber, B. F. Belgardt, L. Koch, J. Seibler, F. Schwenk, C. L. Plum, X. Ma, B. Hampel, N. Balthasar, R. Coppari, H. Munzberg, M. Shanabrough, D. diet-sensitive obesity Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to

Obesity: global epidemiology and pathogenesis.

Abstract: The prevalence of obesity has increased worldwide in the past ~50 years, reaching pandemic levels. Obesity represents a major health challenge because it substantially increases the risk of diseases such as type 2 diabetes mellitus, fatty liver disease, hypertension, myocardial infarction, stroke, dementia, osteoarthritis, obstructive sleep apnoea and several cancers, thereby contributing to a decline in both quality of life and life expectancy. Obesity is also associated with unemployment, social disadvantages and reduced socio-economic productivity, thus increasingly creating an economic burden. Thus far, obesity prevention and treatment strategies - both at the individual and population level - have not been successful in the long term. Lifestyle and behavioural interventions aimed at reducing calorie intake and increasing energy expenditure have limited effectiveness because complex and persistent hormonal, metabolic and neurochemical adaptations defend against weight loss and promote weight regain. Reducing the obesity burden requires approaches that combine individual interventions with changes in the environment and society. Therefore, a better understanding of the remarkable regional differences in obesity prevalence and trends might help to identify societal causes of obesity and provide guidance on which are the most promising intervention strategies.

Post-transcriptional gene regulation by mRNA modifications

Abstract: The recent discovery of reversible mRNA methylation has opened a new realm of post-transcriptional gene regulation in eukaryotes. The identification and functional characterization of proteins that specifically recognize RNA N6-methyladenosine (m6A) unveiled it as a modification that cells utilize to accelerate mRNA metabolism and translation. N6-adenosine methylation directs mRNAs to distinct fates by grouping them for differential processing, translation and decay in processes such as cell differentiation, embryonic development and stress responses. Other mRNA modifications, including N1-methyladenosine (m1A), 5-methylcytosine (m5C) and pseudouridine, together with m6A form the epitranscriptome and collectively code a new layer of information that controls protein synthesis.

Gene expression regulation mediated through reversible m 6 A RNA methylation

Abstract: Cellular RNAs carry diverse chemical modifications that used to be regarded as static and having minor roles in 'fine-tuning' structural and functional properties of RNAs. In this Review, we focus on reversible methylation through the most prevalent mammalian mRNA internal modification, N(6)-methyladenosine (m(6)A). Recent studies have discovered protein 'writers', 'erasers' and 'readers' of this RNA chemical mark, as well as its dynamic deposition on mRNA and other types of nuclear RNA. These findings strongly indicate dynamic regulatory roles that are analogous to the well-known reversible epigenetic modifications of DNA and histone proteins. This reversible RNA methylation adds a new dimension to the developing picture of post-transcriptional regulation of gene expression.

Reading, writing and erasing mRNA methylation.

Abstract: RNA methylation to form N6-methyladenosine (m6A) in mRNA accounts for the most abundant mRNA internal modification and has emerged as a widespread regulatory mechanism that controls gene expression in diverse physiological processes. Transcriptome-wide m6A mapping has revealed the distribution and pattern of m6A in cellular RNAs, referred to as the epitranscriptome. These maps have revealed the specific mRNAs that are regulated by m6A, providing mechanistic links connecting m6A to cellular differentiation, cancer progression and other processes. The effects of m6A on mRNA are mediated by an expanding list of m6A readers and m6A writer-complex components, as well as potential erasers that currently have unclear relevance to m6A prevalence in the transcriptome. Here we review new and emerging methods to characterize and quantify the epitranscriptome, and we discuss new concepts - in some cases, controversies - regarding our understanding of the mechanisms and functions of m6A readers, writers and erasers.