Activation of mammalian target of rapamycin induces lipid accumulation in the diaphragm of ventilated rats and hypoxia-treated C2C12 cells

Yu, Tao; Wen, Yadong; Cao, Yingya; Shen, Guanggui; Jiang, Xinyan; Wu, Jingyi; Lü, Weihua; Jin, Xiaoju

doi:10.1016/j.jss.2017.12.038

Cited by 5 publications

(2 citation statements)

References 26 publications

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“…Depletion of mTOR reduces lipid accumulation and inhibits adipocyte differentiation, and PPARγ can reverse the impaired adipogenesis caused by mTOR deletion (30). In addition, the mTOR-specific inhibitor, rapamycin, can inhibit adipogenic differentiation (36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

Kindlin-2 regulates the differentiation of 3T3-L1 preadipocytes: implications for wound healing

et al. 2021

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Background: Adipose tissue has been proven to play a crucial role in wound healing, while kindlin-2, an integrin-associated protein, has been shown to regulate cell adhesion, migration, and differentiation. This study aimed to explore its involvement in the cell differentiation of 3T3-L1 preadipocytes and its role in wound healing.Methods: Cell adhesion, Cell Counting Kit-8 (CCK-8), Transwell, and in vitro wound healing assays, along with adipogenic and osteogenic differentiation induction were performed in 3T3-L1 preadipocytes in which kindlin-2 was knocked down or overexpressed. In vivo, kindlin-2 (+/−) transgenic mice were constructed, and wound healing was analyzed by immunohistochemistry (IHC) in a mouse dorsal wound model. Realtime polymerase chain reaction (RT-PCR) and western blotting were performed to analyze the expression of adipokines and adipogenic markers in mouse wound tissues. Adipogenic differentiation induction of adipose tissue stromal vascular fraction (SVF) were performed, and the expression of adipogenic markers in SVF was detected by western blotting. The target signaling pathway highly related to adipogenic differentiation was explored by computational biology and verified by western blotting.Results: Knockdown of kindlin-2 was found to inhibit the adhesion, migration, and adipogenic differentiation of 3T3-L1 preadipocytes while promoting their osteogenic differentiation. In contrast, kindlin-2 overexpression resulted in increased adhesion, migration, and adipogenic differentiation of 3T3-L1 preadipocytes while reducing osteogenic differentiation. In vivo, downregulation of kindlin-2 inhibited adipogenesis in kindlin-2 transgenic mice, resulting in delayed wound healing by inhibiting inflammation, angiogenesis, collagen remodeling, and wound contraction. Mechanistically, we found that kindlin-2 could regulate adipogenic differentiation through PI3K/AKT/mTOR signaling pathway.Conclusions: Our study revealed the essential role that kindlin-2 has in the differentiation and wound healing of 3T3-L1 preadipocytes, which offers a theoretical basis for further research and a novel strategy for wound healing.

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Section: Discussionmentioning

confidence: 99%

Kindlin-2 regulates the differentiation of 3T3-L1 preadipocytes: implications for wound healing

et al. 2021

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“…As key molecules mediating the Akt–mTOR signalling pathway in protein synthesis, the protein expression levels of Akt and mTOR are significantly decreased in the diaphragm after mechanical ventilation, as is the protein expression of the downstream target 4E‐BP1 (Hudson et al., 2015; Yu et al., 2018). Moreover, gastrocnemius myofibrillar protein content and synthesis (in milligrams per day) have been shown to decrease significantly (by 26 and 64%, respectively) in rats undergoing tail suspension (Linderman et al., 1994).…”

Section: Discussionmentioning

confidence: 99%

Differential protein metabolism and regeneration in hypertrophic diaphragm and atrophic gastrocnemius muscles in hibernating Daurian ground squirrels

Xia

Gao

Niu

et al. 2021

Experimental Physiology

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Are differences in the regulation of protein metabolism and regeneration involved in the different phenotypic adaptation mechanisms of muscle hypertrophy and atrophy in hibernators? Two fast-type muscles (diaphragm and gastrocnemius) in summer active and hibernating Daurian ground squirrels were selected to detect changes in crosssectional area (CSA) and protein expression indicative of protein synthesis metabolism (protein expression of P-Akt, P-mTORC1, P-S6K1 and P-4E-BP1), protein degradation metabolism (MuRF1, atrogin-1, calpain-1, calpain-2, calpastatin, desmin, troponin T, Beclin1 and LC3-II) and muscle regeneration (MyoD, myogenin and myostatin). In the hibernation group compared with the summer active group, the CSA of the diaphragm muscle increased significantly by 26.1%, whereas the CSA of the gastrocnemius muscle decreased significantly by 20.4%. Our study also indicated that increased protein synthesis, decreased protein degradation and increased muscle regenerative potential contributed to diaphragm muscle hypertrophy, whereas decreased protein synthesis, increased protein degradation and decreased muscle regenerative potential contributed to gastrocnemius muscle atrophy. In conclusion, the differences in muscle regeneration and regulatory pattern of protein metabolism might contribute to the different adaptive changes observed in the diaphragm and gastrocnemius muscles of ground squirrels.

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Differential protein metabolism and regeneration in hypertrophic diaphragm and atrophic gastrocnemius muscles in hibernating Daurian ground squirrels

Xia

Gao

Peng

et al. 2019

Preprint

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41Whether differences in regulation of protein metabolism and regeneration are involved in the 42 different phenotypic adaptation mechanisms of muscle hypertrophy and atrophy in hibernators? 43Two fast-type muscles (diaphragm and gastrocnemius) in summer active and hibernating Daurian 44 ground squirrels were selected to detect changes in cross-sectional area (CSA), fiber type 45 distribution, and protein expression indicative of protein synthesis metabolism (protein expression 46 of P-Akt, P-mTORC1, P-S6K1, and P-4E-BP1), protein degradation metabolism (MuRF1, atrogin-47 1, calpain-1, calpain-2, calpastatin, desmin, troponin T, Beclin1, and LC3-II), and muscle 48 regeneration (MyoD, myogenin, and myostatin). Results showed the CSA of the diaphragm muscle 49 increased significantly by 26.1%, whereas the CSA of the gastrocnemius muscle decreased 50 significantly by 20.4% in the hibernation group compared with the summer active group. Both 51 muscles displayed a significant fast-to-slow fiber-type transition in hibernation. Our study further 52 indicated that increased protein synthesis, decreased protein degradation, and increased muscle 53 regeneration potential contributed to diaphragm muscle hypertrophy, whereas decreased protein 54 synthesis, increased protein degradation, and decreased muscle regeneration potential contributed 55 to gastrocnemius muscle atrophy. In conclusion, the differences in muscle regeneration and 56 regulatory pattern of protein metabolism may contribute to the different adaptive changes observed 57 in the diaphragm and gastrocnemius muscles of ground squirrels. 58 59

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Activation of mammalian target of rapamycin induces lipid accumulation in the diaphragm of ventilated rats and hypoxia-treated C2C12 cells

Cited by 5 publications

References 26 publications

Kindlin-2 regulates the differentiation of 3T3-L1 preadipocytes: implications for wound healing

Kindlin-2 regulates the differentiation of 3T3-L1 preadipocytes: implications for wound healing

Differential protein metabolism and regeneration in hypertrophic diaphragm and atrophic gastrocnemius muscles in hibernating Daurian ground squirrels

Differential protein metabolism and regeneration in hypertrophic diaphragm and atrophic gastrocnemius muscles in hibernating Daurian ground squirrels

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