Increased glucose metabolism in Arid5b−/− skeletal muscle is associated with the down-regulation of TBC1 domain family member 1 (TBC1D1)

Abstract

Background Skeletal muscle has an important role in regulating whole-body energy homeostasis, and energy production depends on the efficient function of mitochondria. We demonstrated previously that AT-rich interactive domain 5b (Arid5b) knockout (Arid5b−/−) mice were lean and resistant to high-fat diet (HFD)-induced obesity. While a potential role of Arid5b in energy metabolism has been suggested in adipocytes and hepatocytes, the role of Arid5b in skeletal muscle metabolism has not been studied. Therefore, we investigated whether energy metabolism is altered in Arid5b−/− skeletal muscle. Results Arid5b−/− skeletal muscles showed increased basal glucose uptake, glycogen content, glucose oxidation and ATP content. Additionally, glucose clearance and oxygen consumption were upregulated in Arid5b−/− mice. The expression of glucose transporter 1 (GLUT1) and 4 (GLUT4) in the gastrocnemius (GC) muscle remained unchanged. Intriguingly, the expression of TBC domain family member 1 (TBC1D1), which negatively regulates GLUT4 translocation to the plasma membrane, was suppressed in Arid5b−/− skeletal muscle. Coimmunofluorescence staining of the GC muscle sections for GLUT4 and dystrophin revealed increased GLUT4 localization at the plasma membrane in Arid5b−/− muscle. Conclusions The current study showed that the knockout of Arid5b enhanced glucose metabolism through the downregulation of TBC1D1 and increased GLUT4 membrane translocation in skeletal muscle.

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“…Functional enrichment analysis additionally indicated that myld-CpGs encompass a diverse range of receptor signalling, immune cell activation, chemokine and metabolic-related processes and pathways (Figure 1E). Although annotated to n=449 genes, we found AT-Rich Interaction Domain 5B (ARID5B), a transcriptional co factor which has been shown to regulate glucose metabolism (24), contained the most myld-CpGs (Figure 1F, Table S1)…”

A High-Density Genetic Map and QTL Fine Mapping for Growth- and Sex-Related Traits in Red Swamp Crayfish (Procambarus clarkii)

“…A total of 11 candidate growth-related genes from 28 growth-related QTL regions were identified d by QTL mapping. It has been reported that TBC1 domain family member 1 ( tbcd1 ) is involved in the regulation of glucose transporter protein 4 transport and glucose uptake in adipocytes and skeletal muscle ( Treebak et al, 2010 ), and downregulation of tbcd1 is associated with enhanced glucose metabolism in mouse skeletal muscle ( Okazaki et al, 2020 ). Golgin subfamily B member 1 ( golgb1 ) encodes golgi-associated large transmembrane protein, and it suggests that a novel 65bp was significantly associated with chicken body weight and significantly associated with neck weight and abdominal fat weight ( Linstedt and Hauri, 1993 ; Fu et al, 2020 ).…”

Correction to: Increased glucose metabolism in Arid5b−/− skeletal muscle is associated with the down-regulation of TBC1 domain family member 1 (TBC1D1)

“…Following publication of the original article [ 1 ], the authors identified a mistake in the acknowledgement section.…”