Autophagosomes accumulate in differentiated and hypertrophic adipocytes in a p53-independent manner

Mikami, Kentaro; Okita, Naoyuki; Tokunaga, Yuki; Ichikawa, Tomoyo; Okazaki, Takuya; Takemoto, Kanako; Nagai, Wataru; Matsushima, Shin; Higami, Yoshikazu

doi:10.1016/j.bbrc.2012.09.134

Cited by 21 publications

(23 citation statements)

References 25 publications

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“…This hypothesis is in agreement with our results demonstrating an increase in mtDNA content and reduction of mitophagy after forced mitochondrial p53 relocation. On the other hand, although mitophagy may be regulated by p53 (8,35), it has never been directly associated with p53 mitochondrial relocation. The inhibition of neural differentiation-elicited mtDNA decrease and mitophagy that we observed in RECQL4-Wt-transfected cells might be partially explained by an indirect effect of mitochondrial p53 in regulating ROS and mtDNA damage.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Translocation of p53 Modulates Neuronal Fate by Preventing Differentiation-Induced Mitochondrial Stress

Xavier

Morgado

Solá

et al. 2014

Antioxidants & Redox Signaling

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Section: Discussionmentioning

confidence: 99%

Mitochondrial Translocation of p53 Modulates Neuronal Fate by Preventing Differentiation-Induced Mitochondrial Stress

Xavier

Morgado

Solá

et al. 2014

Antioxidants & Redox Signaling

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“…For CTSB overexpression, mock and CTSB-overexpressing 3T3L1 cell lines (CTSB [OE]) were generated using a retroviral system with pMXs-Puro-AMNN vector. Preadipocyte cell lines were differentiated into mature adipocytes as previously reported 20,55,56 . Day 8 to 12 3T3L1 adipocytes, which were fully differentiated with accumulated TG, were used in this study.…”

Section: Methodsmentioning

confidence: 99%

“…Signals were detected with an LAS-3000 image analyzer (Fujifilm, Tokyo, Japan) and analyzed using Multigauge software (Fujifilm) as described previously 20,55,56 . LC3 (PM036), SQSTM1 (PM045), ATG5 (M153–3), BECN1 (PD017) and LMNB1/Lamin B1 (PM064) were purchased from MBL.…”

Section: Methodsmentioning

confidence: 99%

Involvement of lysosomal dysfunction in autophagosome accumulation and early pathologies in adipose tissue of obese mice

et al. 2017

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Whether obesity accelerates or suppresses autophagy in adipose tissue is still debatable. To clarify dysregulation of autophagy and its role in pathologies of obese adipose tissue, we focused on lysosomal function, protease maturation and activity, both in vivo and in vitro. First, we showed that autophagosome formation was accelerated, but autophagic clearance was impaired in obese adipose tissue. We also found protein and activity levels of CTSL (cathepsin L) were suppressed in obese adipose tissue, while the activity of CTSB (cathepsin B) was significantly enhanced. Moreover, cellular senescence and inflammasomes were activated in obese adipose tissue. In 3T3L1 adipocytes, downregulation of CTSL deteriorated autophagic clearance, upregulated expression of CTSB, promoted cellular senescence and activated inflammasomes. Upregulation of CTSB promoted additional activation of inflammasomes. Therefore, we suggest lysosomal dysfunction observed in obese adipose tissue leads to lower autophagic clearance, resulting in autophagosome accumulation. Simultaneously, lysosomal abnormalities, including deteriorated CTSL function and compensatory activation of CTSB, caused cellular senescence and inflammasome activation. Our findings strongly suggest lysosomal dysfunction is involved in early pathologies of obese adipose tissue.

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“…Obesity is associated with increased accumulation of autophagosomes, an attenuated mTOR signaling, as well as enhanced expression of key autophagy-related proteins beclin-1, ATG5, ATG7, ATG12, and LC3B (166,167,201,268). Markers of autophagy are correlated with whole body adiposity, visceral fat distribution, and adipocyte hypertrophy (167,268).…”

Section: Biological and Morphological Changes Of White Adipose Tissuementioning

confidence: 99%

Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism

Rodrı́guez

Ezquerro

Méndez‐Giménez

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

242

186

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Adipose tissue constitutes an extremely active endocrine organ with a network of signaling pathways enabling the organism to adapt to a wide range of different metabolic challenges, such as starvation, stress, infection, and short periods of gross energy excess. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a huge variety of hormones, cytokines, complement and growth factors, extracellular matrix proteins, and vasoactive factors, collectively termed adipokines. Obesity is associated with adipose tissue dysfunction leading to the onset of several pathologies including type 2 diabetes, dyslipidemia, nonalcoholic fatty liver, or hypertension, among others. The mechanisms underlying the development of obesity and its associated comorbidities include the hypertrophy and/or hyperplasia of adipocytes, adipose tissue inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. Recently, the potential role of brown and beige adipose tissue in the protection against obesity has been also recognized. In contrast to white adipocytes, which store energy in the form of fat, brown and beige fat cells display energy-dissipating capacity through the promotion of triacylglycerol clearance, glucose disposal, and generation of heat for thermogenesis. Identification of the morphological and molecular changes in white, beige, and brown adipose tissue during weight gain is of utmost relevance for the identification of pharmacological targets for the treatment of obesity and its associated metabolic diseases. white and brown adipogenesis; fat browning; adipocyte hypertrophy and hyperplasia; adipose tissue inflammation; extracellular matrix remodeling THE ADIPOSE ORGAN REPRESENTS a special loose connective tissue containing adipocytes and several cell types surrounded by capillary and innervation networks (47, 79, 82). Adipocytes comprise ϳ35-70% of adipose mass, and the other cell types found in the stroma-vascular fraction include preadipocytes, mesenchymal stem cells, macrophages and other immune cells, and endothelial and smooth muscle cells, among others (79). The classical functions of adipose tissue are the storage of energy in the form of triacylglycerols (TG) and as thermal insulator. Adipocytes were formerly classified into two main types: white adipocytes, which store energy in the form of fat, and brown adipocytes, which induce thermogenesis (82). The current classification scheme includes a third category of adipocytes, termed beige or brite (brown-in-white) adipocytes, which can be considered inducible brown-like cells with thermogenic properties (340). Since the identification of leptin in 1994 (359), adipose tissue has emerged as an extremely active endocrine organ that secretes a huge variety of hormones, cytokines, growth factors, and vasoactive factors that are collectively termed adipokines (67, 81,235,262). Over the last three decades, overwhelming evidence has proven that adipokines not only influence adipobiol...

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Autophagosomes accumulate in differentiated and hypertrophic adipocytes in a p53-independent manner

Cited by 21 publications

References 25 publications

Mitochondrial Translocation of p53 Modulates Neuronal Fate by Preventing Differentiation-Induced Mitochondrial Stress

Mitochondrial Translocation of p53 Modulates Neuronal Fate by Preventing Differentiation-Induced Mitochondrial Stress

Involvement of lysosomal dysfunction in autophagosome accumulation and early pathologies in adipose tissue of obese mice

Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism

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