Biology subjects

Yoneshiro, T.

Publications and source records attributed to Yoneshiro, T..

4 recordsLinked to original sources

bioRxiv2024

Large-scale generation of uniform sub-100 μm adipocyte spheroids in hydrogel microcapsules using a flow-focusing microfluidic device

Adipocyte spheroids are a promising three-dimensional (3D) cell culture model for obesity research because they reproduce 3D adipose tissue structures and cell-cell interactions better than 2D cultures. However, current methods fail to produce uniformly sized, small adipocyte spheroids at large scales, significantly limiting their use in analysis such as large-scale drug screening. Here, we develop a scalable method that combines simple microfluidics with templated emulsification to generate small, uniformly sized adipocyte spheroids. By encapsulating preadipocytes in numerous hollow agarose microcapsules and incubating them for two days, we reproducibly produced more than 100,000 uniform spheroids with diameters of approximately 50 {micro}m (CV: <13%); we then differentiated preadipocyte spheroids into adipocyte spheroids after an 8-day induction period. Our platform enhances large-scale 3D analysis using adipocyte spheroids for obesity research and can be adapted to generate various spheroid and organoid models, advancing biomedical research across diverse fields.

bioengineering↗

bioRxiv2024

Brown Adipose Tissue and Skeletal Muscle Coordinately Contribute to Thermogenesis in Mice

Endotherms increase the rate of metabolism in metabolic organs as one strategy to cope with a decline in temperature of the external environment. However, an additional major contributor to maintenance of body temperature in a cold environment is contraction-based thermogenesis in skeletal muscle. Here, we show that impairment of hind limb muscle contraction by cast immobilization induced a loss of function of skeletal muscle and activated brown adipose tissue (BAT) thermogenesis as a compensatory mechanism. BAT utilizes free branched-chain amino acids (BCAAs) derived from skeletal muscle as an energy substrate for thermogenesis, and interleukin-6 released by skeletal muscle stimulates BCAAs production in muscle for support of BAT thermogenesis. Additionally, this thermoregulatory system between BAT and skeletal muscle may also play an important role in response to cold temperatures or acute stress. Our findings suggest that BAT and skeletal muscle cooperate to maintain body temperature in endotherms.

molecular biology↗

bioRxiv2021

Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever

Importing necessary metabolites into the mitochondrial matrix is a crucial step of fuel choice during stress adaptation. Branched chain-amino acids (BCAA, Valine, Leucine, and Isoleucine) are essential for anabolic processes like protein synthesis, but they are also imported into the mitochondria for catabolic reactions. What controls the distinct subcellular BCAA utilization during stress adaptation is insufficiently understood. The present study reports the role of SLC25A44, a recently identified mitochondrial BCAA carrier (MBC), in the regulation of mitochondrial BCAA catabolism and adaptive response to fever. We found that mitochondrial BCAA oxidation in brown adipose tissue (BAT) is significantly enhanced during fever in response to the pyrogenic mediator prostaglandin E2 (PGE2) and psychological stress. Genetic deletion of MBC in a BAT-specific manner blunts mitochondrial BCAA oxidation and non-shivering thermogenesis following intracerebroventricular PGE2 administration. At a cellular level, MBC is required for mitochondrial BCAA deamination as well as the synthesis of mitochondrial amino acids and TCA intermediates. Together, these results illuminate the role of MBC as a determinant of metabolic flexibility to mitochondrial BCAA catabolism and optimal febrile responses. This study also offers an opportunity to control fever by rewiring the subcellular BCAA fate.

cell biology↗

bioRxiv2019

Loss of a novel striated muscle-enriched mitochondrial protein Coq10a enhances postnatal cardiac hypertrophic growth

Postnatal mammalian cardiomyocytes undergo a major transition from hyperplasia (increases in cell numbers) to hypertrophy (expansion in cell size). This process is accompanied by rapid mitochondrial biogenesis and metabolic switches to meet the demand of increased cardiac output. Although most mitochondrial components express ubiquitously, recent transcriptomic and proteomic analyses have discovered numerous tissue-specific mitochondrial proteins whose physiological functions are largely unknown. Here we report that a highly evolutionarily conserved mitochondrial protein Coq10a is predominantly expressed in mammalian cardiac and skeletal muscles, and is highly up-regulated around birth in a thyroid hormone-dependent manner. Deletion of Coq10a by CRISPR/Cas9 leads to enhanced cardiac growth after birth. Surprisingly, adult Coq10a mutant mice maintain the hypertrophic heart phenotype with increased levels of coenzyme Q (CoQ) per cardiomyocyte, preserved cardiac contractile function and mitochondrial respiration, which contrasts with reported mice and humans with mutations in other Coq family genes. Further RNA-seq analysis and mitochondrial characterization suggest an increase of mitochondrial biogenesis in the Coq10a mutant heart as a possible consequence of Peroxisome proliferator-activated receptor Gamma Coactivator 1-alpha (PGC1) activation, consistent with a recent intriguing report that CoQ may function as a natural ligand and partial agonist of Peroxisome Proliferator-Activated Receptor (PPAR) /{gamma}. Taken together, our study reveals a previously unknown function of a novel striated muscle-enriched mitochondrial protein Coq10a in regulating postnatal heart growth.

developmental biology↗