• Fisheries and Aquatic Sciences
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• v.26 no.6
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• pp.406-422
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• 2023

Sarcopenia is an age-related, progressive skeletal muscle disorder involving the loss of muscle mass and strength. Previous studies have shown that γ-aminobutyric acid (GABA) from fermented oysters aids in regulatory T cells (Tregs) cell expansion and function by enhancing autophagy, and concomitantly mediate muscle regeneration by modulating muscle inflammation and satellite cell function. The fermentation process of oysters not only increases the GABA content but also enhances the content of branched amino acids and free amino acids that aid the level of protein absorption and muscle strength, mass, and repair. In this study, the effect of GABA-enriched fermented sarco oyster extract (FSO) on reduced muscle mass and functions via Treg modulation and enhanced autophagy in aged mice was investigated. Results showed that FSO enhanced the expression of autophagy markers (autophagy-related gene 5 [ATG5] and GABA receptor-associated protein [GABARAP]), forkhead box protein 3 (FoxP3) expression, and levels of anti-inflammatory cytokines (interleukin [IL]-10 and transforming growth factor [TGF]-β) secreted by Tregs while reducing pro-inflammatory cytokine levels (IL-17A and interferon [IFN]-γ). Furthermore, FSO increased the expression of IL-33 and its receptor IL-1 receptor-like 1 (ST2); well-known signaling pathways that increase amphiregulin (Areg) secretion and expression of myogenesis markers (myogenic factor 5, myoblast determination protein 1, and myogenin). Muscle mass and function were also enhanced via FSO. Overall, the current study suggests that FSO increased autophagy, which enhanced Treg accumulation and function, decreased muscle inflammation, and increased satellite cell function for muscle regeneration and therefore could decrease the loss of muscle mass and function with aging.

• Nutrition Research and Practice
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• v.15 no.6
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• pp.673-685
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• 2021

BACKGROUND/OBJECTIVES: Obesity is associated with the impaired regulation of T cells characterized by increased numbers of Th1 and Th17 cells and the dysregulation of vitamin D metabolism. Both obesity and vitamin D have been reported to affect autophagy; however, a limited number of studies have investigated the effects of vitamin D on T cell autophagy in obese mice. Therefore, we aimed to determine whether in vitro treatment with vitamin D affects the proliferation, function, and autophagy of T cells from obese and control mice. MATERIALS/METHODS: Five-week-old male C57BL/6 mice were fed control or high-fat diets (10% or 45% kcal fat: CON or HFDs, respectively) for 12 weeks. Purified T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies and cultured with either 10 nM 1,25(OH)₂D₃ or 0.1% ethanol (vehicle control). The proliferative response; expression of CD25, Foxp3, RORγt, and autophagy-related proteins (LC3A/B, SQSTM1/P62, BECLIN-1, ATG12); and the production of interferon (IFN)-γ, interleukin (IL)-4, IL-17A, and IL-10 by T cells were measured. RESULTS: Compared with the CON group, T cell proliferation tended to be lower, and the production of IFN-γ was higher in the HFD group. IL-17A production was reduced by 1,25(OH)2D₃ treatment in both groups. The LC3 II/I ratio was higher in the HFD group than the CON group, but P62 did not differ. We observed no effect of vitamin D treatment on T cell autophagy. CONCLUSIONS: Our findings suggest that diet-induced obesity may impair the function and inhibit autophagy of T cells, possibly leading to the dysregulation of T cell homeostasis, which may be behind the aggravation of inflammation commonly observed in obesity.

• Reproductive and Developmental Biology
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• v.37 no.4
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• pp.269-279
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• 2013

Low efficiency of somatic cell nuclear transfer (SCNT) is attributed to incomplete reprogramming of transfered nuclei into oocytes. Trichostatin A (TSA), histone deacetylase inhibitor and 5-aza-2'deoxycytidine (5-aza-dC), DNA methylation inhibitor has been used to enhance nuclear reprogramming following SCNT. However, it was not known molecular mechanism by which TSA and 5-aza-dC improve preimplantation embryo and fetal development following SCNT. The present study investigates embryo viability and gene expression of cloned porcine preimplantation embryos in the presence and absence of TSA and 5-aza-dC as compared to embryos produced by parthenogenetic activation. Our results indicated that TSA treatment significantly improved development. However 5-aza-dC did not improve development. Presence of TSA and 5-aza-dC significantly improved total cell number, and also decreased the apoptotic and autophagic index. Three apoptotic-related genes, Bak, Bcl-xL, and Caspase 3 (Casp3), and three autophagic-related genes, ATG6, ATG8, and lysosomal-associated membrane protein 2 (LAMP2), were measured by real time RT-PCR. TSA and 5-aza-dC treatment resulted in high expression of anti-apoptotic gene Bcl-xL and low pro-apoptotic gene Bak expression compared to untreated NT embryos or parthenotes. Furthermore, LC3 protein expression was lower in NT-TSA and NT-5-aza-dC embryos than those of NT and parthenotes. In addition, TSA and 5-aza-dC treated embryos displayed a global acetylated histone H3 at lysine 9 and methylated DNA H3 at lysine 9 profile similar to the parthenogenetic blastocysts. Finally, we determined that several DNA methyltransferase genes Dnmt1, Dnmt3a and Dnmt3b. NT blastocysts showed higher levels Dnmt1 than those of the TSA and 5-aza-dC blastocysts. Dnmt3a is lower in 5-aza-dC than NT, NTTSA and parthenotes. However, Dnmt3b is higher in 5-aza-dC than NT and NTTSA. These results suggest that TSA and 5-aza-dC positively regulates nuclear reprogramming which result in modulation of apoptosis and autophagy related gene expression and then reduce apoptosis and autophagy. In addition, TSA and 5-aza-dC affects the acetylated and methylated status of the H3K9.