Novel role of autophagy-associated Pik3c3 gene in gonadal white adipose tissue browning in aged C57/Bl6 male mice

Ghosh, Amiya K.; Mau, Theresa; O’Brien, Martin; Yung, Raymond

doi:10.18632/aging.101426

Cited by 11 publications

(8 citation statements)

References 42 publications

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“…Meanwhile, antioxidant enzymes, the most important defenders that significantly reduce the toxicity of ROS, have a protective effect against the adverse effects of lipid peroxidation [29]. Nevertheless, antioxidant enzymes, including GPx, SOD, and CAT, cannot effectively eliminate the increased amount of ROS due to persistent or severe HS, which induces an imbalance in redox status in vivo, resulting in excessive accumulation of MDA and oxidative damage to the tissue [30,31]. In this study, histological analysis of testicular tissue sections showed that HS caused abnormalities in the spermatogenic cell layers in seminiferous tubules, whereas these abnormalities were rarely observed in the ALA + HS treatment group.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Endoplasmic Reticulum Stress Are Involved in the Protective Effect of Alpha Lipoic Acid Against Heat Damage in Chicken Testes

Xiong

Yin

et al. 2020

Animals

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Heat stress (HS) causes testicular injury, resulting in decreased fertility. Alpha-lipoic acid (ALA) is a well-known antioxidant. The aim of this study was to investigate the protective effects of ALA on HS-induced testicular damage in chickens. Histological changes; biomarkers of oxidative stress, including glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA); markers of endoplasmic reticulum (ER) stress, including glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP); apoptosis-related modulators, including Bax, Bcl-2, and caspase 3, in testicular tissue and serum testosterone levels were evaluated in chickens under heat stress. Heat stress induces spermatogenic cell abnormalities in chicken testes. Compared to the HS group, the histomorphological abnormalities in testicular tissue were visibly ameliorated, with significant increases in the enzyme activities of GPx, SOD, and CAT, increased serum testosterone concentration, and decreased MDA levels in the ALA + HS group. Consistent with these results, compared with the HS group, the protein levels of GRP78, CHOP, caspase 3, and Bax were significantly decreased, whereas Bcl-2, StAR, and 3β-HSD protein levels were increased in the ALA + HS group. Collectively, these findings suggest that ALA significantly ameliorates the heat-induced histomorphological abnormalities in the testes and decreased testosterone production by potentiating the activities of anti-oxidative enzymes (GPx, SOD, and CAT), inhibiting ER stress-related apoptotic pathways (Bax, Bcl-2, and caspase 3), and increasing steroidogenic gene (StAR and 3β-HSD) expression in chickens.

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Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Endoplasmic Reticulum Stress Are Involved in the Protective Effect of Alpha Lipoic Acid Against Heat Damage in Chicken Testes

Xiong

Yin

et al. 2020

Animals

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“…The PIK3C3-ATG14 complex induces autophagy especially in nutrient-stress conditions such as starvation (Yuan et al, 2013). Recently, it has been shown that in aged mice with a PIK3C3 mutation, compared to fl/fl control mice, adipogenesis markers, such as AP2 and C/EBP-α, are reduced, but brown adipose-specific markers, such as UCP1 and PPAR- γ coactivator (PGC)1α, are enhanced in both mRNA and protein levels in the gonadal WAT (gWAT), possibly through blocking of autophagy (Ghosh et al, 2018).…”

Section: Autophagy Manipulations In Adipocyte Browningmentioning

confidence: 99%

“…These occur dynamically depending on browning status (Baerga et al, 2009; Singh et al, 2009b; Zhang et al, 2009; Singh and Cuervo, 2012; Li and Ding, 2017; Ghosh et al, 2018). Both autophagy malfunction and adipocyte dysfunction are clearly connected with the causes of metabolic disorders such as obesity and diabetes (Baerga et al, 2009; Singh et al, 2009b; Zhang et al, 2009; Bjorndal et al, 2011; Singh and Cuervo, 2012; Bluher, 2013; Scheele and Nielsen, 2017; Ghosh et al, 2018). To examine this, both mechanistic and clinical studies have investigated the significant relationship between autophagy and browning (Armani et al, 2014; Stienstra et al, 2014).…”

Section: Introduction: Autophagy In Adipocytesmentioning

confidence: 99%

Autophagy in Adipocyte Browning: Emerging Drug Target for Intervention in Obesity

Jang

Bae

et al. 2019

Front. Physiol.

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Autophagy, lipophagy, and mitophagy are considered to be the major recycling processes for protein aggregates, excess fat, and damaged mitochondria in adipose tissues in response to nutrient status-associated stress, oxidative stress, and genotoxic stress in the human body. Obesity with increased body weight is often associated with white adipose tissue (WAT) hypertrophy and hyperplasia and/or beige/brown adipose tissue atrophy and aplasia, which significantly contribute to the imbalance in lipid metabolism, adipocytokine secretion, free fatty acid release, and mitochondria function. In recent studies, hyperactive autophagy in WAT was observed in obese and diabetic patients, and inhibition of adipose autophagy through targeted deletion of autophagy genes in mice improved anti-obesity phenotypes. In addition, active mitochondria clearance through activation of autophagy was required for beige/brown fat whitening – that is, conversion to white fat. However, inhibition of autophagy seemed detrimental in hypermetabolic conditions such as hepatic steatosis, atherosclerosis, thermal injury, sepsis, and cachexia through an increase in free fatty acid and glycerol release from WAT. The emerging concept of white fat browning–conversion to beige/brown fat–has been controversial in its anti-obesity effect through facilitation of weight loss and improving metabolic health. Thus, proper regulation of autophagy activity fit to an individual metabolic profile is necessary to ensure balance in adipose tissue metabolism and function, and to further prevent metabolic disorders such as obesity and diabetes. In this review, we summarize the effect of autophagy in adipose tissue browning in the context of obesity prevention and its potential as a promising target for the development of anti-obesity drugs.

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“…It has been shown that Pik3c3 is a nutrient-regulated lipid kinase that regulates glucose and amino acid for protein synthesis and cell growth through mTOR-S6K1 signaling pathway [32, 33]. In addition, there was evidence that Pik3c3 regulated autophagy activity and correlated with endoplasmic reticulum stress [34]. Here in the study, high-fat diet increased Pik3c3 and 40 s/60 s ribosomal subunit downstream.…”

Section: Discussionmentioning

confidence: 70%

Effects of metformin on metabolism of white and brown adipose tissue in obese C57BL/6J mice

Yuan

Zhao

et al. 2019

Diabetol Metab Syndr

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BackgroundTo investigate effects of metformin on the regulation of proteins of white adipose tissue (WAT) and brown adipose tissue (BAT) in obesity and explore the underlying mechanisms on energy metabolism.MethodsC57BL/6J mice were fed with normal diet (ND, n = 6) or high-fat diet (HFD, n = 12) for 22 weeks. HFD-induced obese mice were treated with metformin (MET, n = 6). After treatment for 8 weeks, oral glucose tolerance test (OGTT) and hyperinsulinemic–euglycemic clamp were performed to evaluate the improvement of glucose tolerance and insulin sensitivity. Protein expressions of WAT and BAT in mice among ND, HFD, and MET group were identified and quantified with isobaric tag for relative and absolute quantification (iTRAQ) coupled with 2D LC–MS/MS. The results were analyzed by MASCOT, Scaffold and IPA.ResultsThe glucose infusion rate in MET group was increased significantly compared with HFD group. We identified 4388 and 3486 proteins in WAT and BAT, respectively. As compared MET to HFD, differential expressed proteins in WAT and BAT were mainly assigned to the pathways of EIF2 signaling and mitochondrial dysfunction, respectively. In the pathways, CPT1a in WAT, CPT1b and CPT2 in BAT were down-regulated by metformin significantly.ConclusionsMetformin improved the body weight and insulin sensitivity of obese mice. Meanwhile, metformin might ameliorate endoplasmic reticulum stress in WAT, and affect fatty acid metabolism in WAT and BAT. CPT1 might be a potential target of metformin in WAT and BAT.

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Novel role of autophagy-associated Pik3c3 gene in gonadal white adipose tissue browning in aged C57/Bl6 male mice

Cited by 11 publications

References 42 publications

Oxidative Stress and Endoplasmic Reticulum Stress Are Involved in the Protective Effect of Alpha Lipoic Acid Against Heat Damage in Chicken Testes

Oxidative Stress and Endoplasmic Reticulum Stress Are Involved in the Protective Effect of Alpha Lipoic Acid Against Heat Damage in Chicken Testes

Autophagy in Adipocyte Browning: Emerging Drug Target for Intervention in Obesity

Effects of metformin on metabolism of white and brown adipose tissue in obese C57BL/6J mice

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