Regulation of gene expression is arguably the main mechanism underlying the phenotypic diversity of tissues within and between species. Here we assembled an extensive transcriptomic dataset covering 8 tissues across 20 bilaterian species and performed analyses using a symmetric phylogeny that allowed the combined and parallel investigation of gene expression evolution between vertebrates and insects. We specifically focused on widely conserved ancestral genes, identifying strong cores of pan-bilaterian tissue-specific genes and even larger groups that diverged to define vertebrate and insect tissues. Systematic inferences of tissue-specificity gains and losses show that nearly half of all ancestral genes have been recruited into tissue-specific transcriptomes. This occurred during both ancient and, especially, recent bilaterian evolution, with several gains being associated with the emergence of unique phenotypes (for example, novel cell types). Such pervasive evolution of tissue specificity was linked to gene duplication coupled with expression specialization of one of the copies, revealing an unappreciated prolonged effect of whole-genome duplications on recent vertebrate evolution.

• MeSH
• fylogeneze MeSH
• hmyz * genetika   MeSH
• molekulární evoluce * MeSH
• obratlovci * genetika   MeSH
• orgánová specificita MeSH
• transkriptom MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: GDF11 is a member of the TGF-β superfamily that was recently implicated as potential "rejuvenating" factor, which can ameliorate metabolic disorders. The main objective of the presented study was to closely characterize the role of GDF11 signaling in the glucose homeostasis and in the differentiation of white adipose tissue. METHODS: We performed microscopy imaging, biochemical and transcriptomic analyses of adipose tissues of 9 weeks old ob/ob mice and murine and human pre-adipocyte cell lines. RESULTS: Our in vivo experiments employing GDF11 treatment in ob/ob mice showed improved glucose/insulin homeostasis, decreased weight gain and white adipocyte size. Furthermore, GDF11 treatment inhibited adipogenesis in pre-adipocytes by ALK5-SMAD2/3 activation in cooperation with the WNT/β-catenin pathway, whose inhibition resulted in adipogenic differentiation. Lastly, we observed significantly elevated levels of the adipokine hormone adiponectin and increased glucose uptake by mature adipocytes upon GDF11 exposure. CONCLUSION: We show evidence that link GDF11 to adipogenic differentiation, glucose, and insulin homeostasis, which are pointing towards potential beneficial effects of GDF11-based "anti-obesity" therapy.

• MeSH
• adipogeneze * MeSH
• adiponektin metabolismus   MeSH
• beta-katenin * metabolismus   MeSH
• buněčná diferenciace fyziologie   MeSH
• glukosa metabolismus   MeSH
• inzulin metabolismus   MeSH
• kostní morfogenetické proteiny metabolismus   MeSH
• lidé MeSH
• myši MeSH
• protein Smad2 MeSH
• protein Smad3 MeSH
• receptory regulované proteiny Smad MeSH
• růstové diferenciační faktory metabolismus   MeSH
• signální dráha Wnt MeSH
• TGF-beta receptor I. typu MeSH
• transformující růstový faktor beta metabolismus   MeSH
• tukové buňky metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adiponektin MeSH
• beta-katenin * MeSH
• GDF11 protein, human MeSH Prohlížeč
• Gdf11 protein, mouse MeSH Prohlížeč
• glukosa MeSH
• inzulin MeSH
• kostní morfogenetické proteiny MeSH
• protein Smad2 MeSH
• protein Smad3 MeSH
• receptory regulované proteiny Smad MeSH
• růstové diferenciační faktory MeSH
• SMAD2 protein, human MeSH Prohlížeč
• Smad2 protein, mouse MeSH Prohlížeč
• SMAD3 protein, human MeSH Prohlížeč
• Smad3 protein, mouse MeSH Prohlížeč
• TGF-beta receptor I. typu MeSH
• TGFBR1 protein, human MeSH Prohlížeč
• Tgfbr1 protein, mouse MeSH Prohlížeč
• transformující růstový faktor beta MeSH

Studies over the past 30 years have revealed that adipose tissue is the major endocrine and paracrine organ of the human body. Arguably, adiopobiology has taken its reasonable place in studying obesity and related cardiometabolic diseases (CMDs), including Alzheimer's disease (AD), which is viewed herein as a neurometabolic disorder. The pathogenesis and therapy of these diseases are multiplex at basic, clinical and translational levels. Our present goal is to describe new developments in cardiometabolic and neurometabolic adipobiology. Accordingly, we focus on adipose- and/or skeletal muscle-derived signaling proteins (adipsin, adiponectin, nerve growth factor, brain-derived neuroptrophic factor, neurotrophin-3, irisin, sirtuins, Klotho, neprilysin, follistatin-like protein-1, meteorin-like (metrnl), as well as growth differentiation factor 11) as examples of metabotrophic factors (MTFs) implicated in the pathogenesis and therapy of obesity and related CMDs. We argue that these pathologies are MTF-deficient diseases. In 1993 the "vascular hypothesis of AD" was published and in the present review we propose the "vasculometabolic hypothesis of AD." We discuss how MTFs could bridge CMDs and neurodegenerative diseases, such as AD. Greater insights on how to manage the MTF network would provide benefits to the quality of human life.

• Klíčová slova
• Alzheimer’s disease, BDNF, Klotho, NGF, adipokines, adiponectin, cardiometabolic diseases, irisin, metabotrophic factors,
• MeSH
• adipokiny metabolismus   MeSH
• cílená molekulární terapie metody   MeSH
• lidé MeSH
• metabolický syndrom farmakoterapie   metabolismus   MeSH
• neurodegenerativní nemoci farmakoterapie   metabolismus   MeSH
• neuropeptidy metabolismus   MeSH
• neurotrofní faktory metabolismus   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• adipokiny MeSH
• neuropeptidy MeSH
• neurotrofní faktory MeSH