Loss of ADAMTS15 Promotes Browning in 3T3-L1 White Adipocytes via Activation of β3-adrenergic Receptor

Choi, Min Ji; Mukherjee, Sulagna; Yun, Jong Won

doi:10.1007/s12257-021-0036-y

Cited by 15 publications

(6 citation statements)

References 40 publications

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“…4,13 More recently, numerous negative regulators of fat browning have been identified, including CYP2E1 41 , CYP2F2 40 , FAM107A, 9 LCP1, 10 and ADAMTS15. 11 The UCP1 protein plays a significant role in regulating the thermogenic program in brown and beige adipocytes, 8 and the upregulation of UCP1 by CYFIP2 deficiency was F I G U R E 6 CYFIP2 deficiency stimulates the browning of 3T3-L1 white adipocytes by inhibiting the GABA-BR pathway. Treatment with the GABA-BR agonist ([R,S]-Baclofen, 100 μM) in combination with the siRNA treatment reduced the expression of ATF4 and abolished the siRNA treatment stimulated an increase in the browning markers.…”

Section: Discussionmentioning

confidence: 99%

“…Apart from classical regulators, such as PRDM16, PGC1α, IRF4, Zfp516, FoxC2, and EHMT1, numerous transcriptional modulators responsible for fat browning have recently been identified 4,13 . More recently, numerous negative regulators of fat browning have been identified, including CYP2E1 41 , CYP2F2 40 , FAM107A, 9 LCP1, 10 and ADAMTS15 11 …”

Section: Discussionmentioning

confidence: 99%

“…8 Adipose tissue development results from a complex transcriptional cascade of adipocyte-specific factors. Recently, several genes have been identified as genetic regulators of beigeing, [9][10][11] and their effects on WAT browning have been confirmed in mouse models. 4,12 The presence of brown and beige adipocytes in human adults has attracted interest as a possible therapeutic intervention for metabolic diseases.…”

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Loss of cytoplasmic FMR1‐interacting protein 2 (CYFIP2) induces browning in 3T3‐L1 adipocytes via repression of GABA‐BR and activation of mTORC1

Manigandan

Yun

2022

J of Cellular Biochemistry

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Obesity and related metabolic disorders are epidemic diseases. Promoting thermogenesis and a functional increase in the browning of white adipocytes may counteract obesity. On the other hand, the molecular mechanism that regulates brown and beige fat-mediated thermogenesis is unclear. This article reports a molecular network led by cytoplasmic FMR1-interacting protein 2 (CYFIP2) that negatively regulates adipocyte browning in white adipocytes. Although the function of CYFIP2 in Fragile X Syndrome (FXS) and autism have been reported, its physiological roles in adipocytes remain elusive. Therefore, this study examined the physiological consequences of its deprivation in cultured 3T3-L1 white adipocytes using loss-of-function studies. Combined real-time quantitative reverse-transcription polymerase chain reaction and immunoblot analysis showed that the loss of CYFIP2 induces fat browning, as evidenced by the gene and protein expression levels of the brown fat-associated markers. A deficiency of CYFIP2 promoted mitochondrial biogenesis and significantly enhanced the expression of the core set beige fat-specific genes (Cd137, Cidea, Cited1, Tbx1, and Tmem26) and proteins (PGC-1α, PRDM16, and UCP1). In addition, a CYFIP2 deficiency promoted lipid catabolism and suppressed adipogenesis, lipogenesis, and autophagy. A mechanistic study showed that the loss of CYFIP2 induces browning in white adipocytes, independently via the activation of mTORC1 and suppression of the GABA-BR signaling pathway. The present data revealed a previously unidentified mechanism of CYFIP2 in the browning of white adipocytes and emphasized the potential of CYFIP2 as a pharmacotherapeutic target for treating obesity and other metabolic disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Loss of cytoplasmic FMR1‐interacting protein 2 (CYFIP2) induces browning in 3T3‐L1 adipocytes via repression of GABA‐BR and activation of mTORC1

Manigandan

Yun

2022

J of Cellular Biochemistry

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“…The treated cells were lysed to extract whole proteins, as previously described (Choi et al 2021). The cytoplasmic and mitochondrial proteins were extracted using a mitochondrial isolation kit, according to the manufacturer's instructions.…”

Section: Western Blot Analysismentioning

confidence: 99%

Induction of apoptosis through inactivation of ROS-dependent PI3K/Akt signaling pathway by platycodin D in human bladder urothelial carcinoma cells

Park¹,

Cha²,

Lee³

et al. 2022

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Platycodin D (PD) is a triterpenoid saponin, a major bioactive constituent of the roots of Platycodon grandiflorum, which is well known for possessing various pharmacological properties. However, the anti-cancer mechanism of PD in bladder cancer cells remains poorly understood.In the current study, we investigated the effect of PD on the growth of human bladder urothelial carcinoma cells. PD treatment significantly reduced the cell survival of bladder cancer cells associated with induction of apoptosis and DNA damage. PD inhibited the expression of inhibitor of apoptosis family members, activated caspases, and induced cleavage of poly (ADP-ribose) polymerase. PD also increased the release of cytochrome c into the cytoplasm by disrupting the mitochondrial membrane potential while upregulating the expression ratio of Bax to Bcl-2. The PD-mediated anti-proliferative effect was significantly inhibited by pre-treatment with a pancaspase inhibitor, but not by an inhibitor of necroptosis. Moreover, PD suppressed the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway, and the apoptosis-inducing effect of PD was further enhanced by a PI3K inhibitor. In addition, PD increased the accumulation of reactive oxygen species (ROS), whereas N-acetyl cysteine (NAC), an ROS inhibitor, significantly attenuated the growth inhibition and inactivation of the PI3K/

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“…To analyze the expression of the target proteins by immunoblotting, cells cultured in the absence or presence of CFE for 1 h were treated with H 2 O 2 for 24 h. Total protein was extracted, as previously mentioned [23] or cytosolic and mitochondrial proteins were isolated for cytochrome c expression analysis using a mitochondrial fraction kit, according to the manufacturer's instructions. After quanti cation of the isolated proteins, samples containing the equal amount of protein were separated on sodium dodecyl sulfate (SDS)-polyacrylamide gels and transferred to PVDF membranes for 1 h at room temperature (RT).…”

Section: Western Blot Analysismentioning

confidence: 99%

Aqueous extracts of Corni Fructus protect C2C12 myoblasts from DNA damage and apoptosis caused by oxidative stress

2022

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Background Although the various pharmacological effects of Corni Fructus are highly correlated with its antioxidant activity, the blocking effect against oxidative stress in muscle cells is not clear. The purpose of this study was to investigate the effect of aqueous extracts of Corni Fructus (CFE) against oxidative stress caused by hydrogen peroxide (H 2 O 2 ) in murine skeletal C2C12 myoblasts.Methods and results MTT assay for cell viability, DCF-DA staining for reactive oxygen species (ROS) production, Comet assay for DNA damage, annexin V-FITC and PI double staining for apoptosis, JC-1 staining and caspase assay for monitor mitochondrial integrity, and western blotting for related protein levels were conducted in H 2 O 2 oxidative stressed C2C12 cells. Our results showed that CFE pretreatment signi cantly ameliorated the loss of cell viability and inhibited apoptosis in H 2 O 2 -treated C2C12 cells in a concentration-dependent manner. DNA damage induced by H 2 O 2 was also markedly attenuated in the presence of CFE, which was associated with suppression of ROS generation. In addition, H 2 O 2 reduced mitochondrial membrane potential and caused downregulation of Bcl-2 and upregulation of Bax expression, although these were abrogated by CFE pretreatment. Moreover, CFE blocked H 2 O 2 -induced cytosolic release of cytochrome c, activation of caspase-9 and caspase-3, and degradation of poly (ADPribose) polymerase.Conclusion Taken together, the present results demonstrate that CFE could protect C2C12 cells from H 2 O 2 -induced damage by eliminating ROS generation, thereby blocking mitochondria-mediated apoptosis pathway. These results indicate that CFE has therapeutic potential for the prevention and treatment of oxidative stress-mediated myoblast injury.

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Loss of ADAMTS15 Promotes Browning in 3T3-L1 White Adipocytes via Activation of β3-adrenergic Receptor

Cited by 15 publications

References 40 publications

Loss of cytoplasmic FMR1‐interacting protein 2 (CYFIP2) induces browning in 3T3‐L1 adipocytes via repression of GABA‐BR and activation of mTORC1

Loss of cytoplasmic FMR1‐interacting protein 2 (CYFIP2) induces browning in 3T3‐L1 adipocytes via repression of GABA‐BR and activation of mTORC1

Induction of apoptosis through inactivation of ROS-dependent PI3K/Akt signaling pathway by platycodin D in human bladder urothelial carcinoma cells

Aqueous extracts of Corni Fructus protect C2C12 myoblasts from DNA damage and apoptosis caused by oxidative stress

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