title: Defective regulation of adipose tissue autophagy in obesity.
abstract: OBJECTIVE
  Autophagy is a highly regulated process that has an important role in the control of a wide range of cellular functions, such as organelle recycling, nutrient availability and tissue differentiation. A recent study has shown an increased autophagic activity in the adipose tissue of obese subjects, and a role for autophagy in obesity-associated insulin resistance was proposed. Body mass reduction is the most efficient approach to tackle insulin resistance in over-weight subjects; however, the impact of weight loss in adipose tissue autophagy is unknown.
  
  
  METHODS
  Adipose tissue autophagy was evaluated in mice and humans.
  
  
  RESULTS
  First, a mouse model of diet-induced obesity and diabetes was maintained on a 15-day, 40% caloric restriction. At baseline, markers of autophagy were increased in obese mice as compared with lean controls. Upon caloric restriction, autophagy increased in the lean mice, whereas it decreased in the obese mice. The reintroduction of ad libitum feeding was sufficient to rapidly reduce autophagy in the lean mice and increase autophagy in the obese mice. In the second part of the study, autophagy was evaluated in the subcutaneous adipose tissue of nine obese-non-diabetic and six obese-diabetic subjects undergoing bariatric surgery for body mass reduction. Specimens were collected during the surgery and approximately 1 year later. Markers of systemic inflammation, such as tumor necrosis factor-1α, interleukin (IL)-6 and IL-1β were evaluated. As in the mouse model, human obesity was associated with increased autophagy, and body mass reduction led to an attenuation of autophagy in the adipose tissue.
  
  
  CONCLUSIONS
  Obesity and caloric overfeeding are associated with the defective regulation of autophagy in the adipose tissue. The studies in obese-diabetic subjects undergoing improved metabolic control following calorie restriction suggest that autophagy and inflammation are regulated independently.
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, Campinas, Brazil.
authors.forename: C E
authors.initials: CE
authors.lastname: Nuñez
authors.forename: V S
authors.initials: VS
authors.lastname: Rodrigues
authors.forename: F S
authors.initials: FS
authors.lastname: Gomes
authors.forename: R F de
authors.initials: RF
authors.lastname: Moura
authors.forename: S C
authors.initials: SC
authors.lastname: Victorio
authors.forename: B
authors.initials: B
authors.lastname: Bombassaro
authors.forename: E A
authors.initials: EA
authors.lastname: Chaim
authors.forename: J C
authors.initials: JC
authors.lastname: Pareja
authors.forename: B
authors.initials: B
authors.lastname: Geloneze
authors.forename: L A
authors.initials: LA
authors.lastname: Velloso
authors.forename: E P
authors.initials: EP
authors.lastname: Araujo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000276:immunology; D000071186:Beclin-1; D015992:Body Mass Index; D031204:Caloric Restriction; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D015390:Gastric Bypass; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D009765:Obesity / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D000071456:Sequestosome-1 Protein; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000378:metabolism; D015431:Weight Loss
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D016207:Cytokines; C490981:Gtf2h1 protein, mouse; D008565:Membrane Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D014157:Transcription Factors; D051758:Transcription Factor TFIIH; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases