Biology subjects

Fujitani, M.

Publications and source records attributed to Fujitani, M..

5 recordsLinked to original sources

bioRxiv2026

Adrβ2 in skeletal muscle cells is required for exercise-induced Pgc1α but not for metabolic benefits of exercise on diet-induced obesity

{beta}2-Adrenergic receptor (Adr{beta}2) is the most abundant form of adrenergic receptors in skeletal muscle. Our previous studies have shown that the ventromedial hypothalamic nucleus (VMH) regulates metabolic benefits of exercise, potentially by skeletal muscle Adr{beta}2. Although a large body of literature has shown the importance of Adr{beta}2 on skeletal muscle physiology, it remains unexplored whether skeletal muscle Adr{beta}2 contributes to metabolic benefits of exercise, such as prevention of diet-induced obesity (DIO). Here, we generated mice lacking Adr{beta}2 in skeletal muscle cells (SKMAdr{beta}2) and tested whether SKMAdr{beta}2 is required for metabolic benefits of exercise on DIO. Deletion of SKMAdr{beta}2 completely abolished the induction of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1) in skeletal muscle by {beta}2-agonist, which is a potent activator of Pgc-1. Exercise upregulates Pgc-1, which regulates a broad range of skeletal muscle physiology, including hypertrophy and mitochondrial function. Deletion of SKMAdr{beta}2 hampers augmented Pgc-1 in skeletal muscle by a single bout of exercise. Intriguingly, we found that deletion of SKMAdr{beta}2 increased endurance capacity. Further, our data showed that body weight in DIO mice lacking SKMAdr{beta}2 is comparable to that of control DIO mice during exercise training, suggesting that deletion of SKMAdr{beta}2 did not affect the metabolic benefits of exercise in DIO. Collectively, our data indicate that SKMAdr{beta}2 contributes to exercise-induced transcriptional changes and endurance capacity, however, it is not required for exercise benefits on bodyweight in DIO mice.

physiology↗

bioRxiv2025

Development and Characterization of a Sf-1-Flp Mouse Model

The use of genetically engineered tools, including combinations of Cre-LoxP and Flp-FRT systems, enable the interrogation of complex biology. Steroidogenic factor-1 (SF-1) is expressed in the ventromedial hypothalamic nucleus (VMH). Development of genetic tools, such as mice expressing Flp recombinase (Flp) in SF-1 neurons (Sf-1-Flp), will be useful for future studies that unravel the complex physiology regulated by the VMH. Here, we developed and characterized Sf-1-Flp mice and demonstrated its utility. Flp sequence was inserted into Sf-1 locus with P2A. This insertion did not affect Sf-1 mRNA expression levels and Sf-1-Flp mice do not have any visible phenotypes. They are fertile and metabolically comparable to wild-type littermate mice. Optogenetic stimulation using adeno-associated virus (AAV)-bearing Flp-dependent channelrhodopsin-2 (ChR2) increased blood glucose and skeletal muscle PGC-1 in Sf-1-Flp mice. This was similar to SF-1 neuronal activation using Sf-1-BAC-Cre and AAV-bearing Cre-dependent ChR2. Finally, we generated Sf-1-Flp mice that lack {beta}2-adrenergic receptors (Adr{beta}2) only in skeletal muscle with a combination of Cre/LoxP technology (Sf-1-Flp::SKM{Delta}Adr{beta}2). Optogenetic stimulation of SF-1 neurons failed to increase skeletal muscle PGC-1 in Sf-1-Flp::SKM{Delta}Adr{beta}2 mice, suggesting that Adr{beta}2 in skeletal muscle is required for augmented skeletal muscle PGC-1 by SF-1 neuronal activation. Our data demonstrate that Sf-1-Flp mice are useful for interrogating complex physiology.

neuroscience↗

bioRxiv2024

Enabling Epitope Analysis of Glycoproteins via HDX-MS Using Antigens with Uni-formed N-linked Glycans

Hydrogen deuterium exchange mass spectrometry (HDX-MS) is widely used for epitope analysis of the antibodies. However, epitope analysis of glycoproteins is challenging because of the heterogeneity of attached N-linked glycans. Recent studies have reported methods where N-linked glycans were removed at low pH following hydrogen deuterium exchange reactions, but the methods for glycoproteins remain controversial. Here, we demonstrate the utility of using antigens with uniformed N-linked glycans in glycoprotein epitope analysis by HDX-MS. By treating HEK293 cells with kifunensine, we were able to prepare antigens mainly with N-linked high-mannose-type glycans. Analysis of epitopes of a monoclonal antibody S309 using antigens prepared with this method allowed us to identify an epitope that included the previously reported N-linked glycan attachment sites for this anti-body. We propose that using antigens with uniformed glycans should be effective for epitope analysis of glycoproteins, such as virus spike proteins covered by glycan shields. Moreover, we believe that this approach accelerates research on vaccines and neutralizing antibodies against viruses that escape host immunity through glycan shields or mutations.

biochemistry↗

bioRxiv2024

Aberrant axon initial segment is an indicator for task-independent neural activity in autism model mice

Autism spectrum disorder (ASD) is a developmental disorder characterized by impairments in several communicative behaviors. Identification of biomarkers for ASD based on task-independent neural activity has been elusive. The axonal initial segment (AIS), located at the proximal part of the axon, is crucial for initiating action potentials (APs) and adaptable through activity-dependent AIS plasticity. In our study, we discovered decrease in AIS length in layer V pyramidal neurons (PyNs) of the prelimbic cortex (PrL) and increase in layer II/III PyNs in the somatosensory cortex of duplicated human 15q11-13 region (15q dup) ASD model mice. Electrophysiological studies using whole-cell patch-clamp recordings in the PrL revealed diminished ability to generate APs. We discovered lack of AIS plasticity in 15q dup mice under conditions of elevated potassium chloride. Retrograde tracing demonstrated that AIS shortening depends on the projection targets. These results indicate that activity-dependent aberrant AIS structures can serve as indicators of altered task-independent neural activity in ASD mouse models.

neuroscience↗

bioRxiv2018

Managing river fish biodiversity generates substantial economic benefits in four European countries

Ecosystems and biodiversity produce benefits to society, but many of them are hard to quantify. For example, it is unclear whether European societies gain benefits from experiencing rivers that host high native biodiversity. Without such knowledge, monetary investments into ecologically oriented river management plans are difficult to justify. The objective of this study was to reveal how the public in four European countries values ecological characteristics of domestic rivers and the outcomes of hypothetical river basin management plans designed to improve river ecosystems, particularly fish biodiversity. We conducted a choice experiment among the populations in Norway, Sweden, Germany and France. We found similar preference structures in all countries with high marginal willingness-to-pay for improvements of abiotic river attributes (increased accessiblity of the river banks, improved bathing water quality, decreased river fragmentation). Citizens also benefited from certain fish species occurring in a river with native salmonid species being more valued than nonnatives, particularly in Norway, and from the degree of a rivers native biodiversity. Welfare measures calculated for selected river basin management plans (policy scenarios) revealed societal benefits that were primarily derived from ecological river management whereas a scenario focusing on hydroelectricity production generated the lowest utility. We conclude that ecological river management may produce high nonmarket economic benefits in all study countries, particularly through the management of abiotic river attributes and the restoration of declining or extinct fish species. Our results help to inform decisions on restoration efforts by showcasing the benefits that these measures have for the public.

ecology↗