title: Autophagosomes accumulate in differentiated and hypertrophic adipocytes in a p53-independent manner.
abstract: Autophagy is induced by several kinds of stress, including oxidative, genotoxic, endoplasmic reticulum and nutrient stresses. The tumor suppressor p53, which is a stress sensor, plays a critical role in the regulation of autophagy. Although p53 is required for starvation (nutrient deficient stress)-induced autophagy, it is still not clear whether p53 is also required for the autophagy observed in differentiated and hypertrophic adipocytes, which accumulate excessive amounts of nutrients in the form of triglycerides. In this study, we demonstrated that starvation induces autophagy in p53-proficient adipocytes, but not in p53-deficient adipocytes as previously reported. On the other hand, autophagy was equally observed in both p53-deficient and -proficient differentiated and hypertrophic adipocytes. Similar results were obtained by in vivo analysis using white adipose tissue of high-fat diet-induced obese mice. Moreover, unexpectedly, the autophagy observed in the differentiated and hypertrophic adipocytes involved increased accumulation of autophagosomes and decreased autophagic flux. Thus, we concluded that in differentiated and hypertrophic adipocytes autophagosomes accumulate in a p53-independent manner, and this accumulation is caused by reduced autophagic flux.
authors.affiliation: Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Mikami
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Okita
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tokunaga
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Okazaki
authors.forename: Kanako
authors.initials: K
authors.lastname: Takemoto
authors.forename: Wataru
authors.initials: W
authors.lastname: Nagai
authors.forename: Shingo
authors.initials: S
authors.lastname: Matsushima
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Higami
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000502:physiology*; D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D049108:Cell Enlargement; D005215:Fasting / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53