title: Long-term intermittent feeding, but not caloric restriction, leads to redox imbalance, insulin receptor nitration, and glucose intolerance.
abstract: Calorie restriction is a dietary intervention known to improve redox state, glucose tolerance, and animal life span. Other interventions have been adopted as study models for caloric restriction, including nonsupplemented food restriction and intermittent, every-other-day feedings. We compared the short- and long-term effects of these interventions to ad libitum protocols and found that, although all restricted diets decrease body weight, intermittent feeding did not decrease intra-abdominal adiposity. Short-term calorie restriction and intermittent feeding presented similar results relative to glucose tolerance. Surprisingly, long-term intermittent feeding promoted glucose intolerance, without a loss in insulin receptor phosphorylation. Intermittent feeding substantially increased insulin receptor nitration in both intra-abdominal adipose tissue and muscle, a modification associated with receptor inactivation. All restricted diets enhanced nitric oxide synthase levels in the insulin-responsive adipose tissue and skeletal muscle. However, whereas calorie restriction improved tissue redox state, food restriction and intermittent feedings did not. In fact, long-term intermittent feeding resulted in largely enhanced tissue release of oxidants. Overall, our results show that restricted diets are significantly different in their effects on glucose tolerance and redox state when adopted long-term. Furthermore, we show that intermittent feeding can lead to oxidative insulin receptor inactivation and glucose intolerance.
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Cerqueira
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: da Cunha
authors.forename: Camille C
authors.initials: CC
authors.lastname: Caldeira da Silva
authors.forename: Bruno
authors.initials: B
authors.lastname: Chausse
authors.forename: Renato L
authors.initials: RL
authors.lastname: Romano
authors.forename: Camila C M
authors.initials: CC
authors.lastname: Garcia
authors.forename: Pio
authors.initials: P
authors.lastname: Colepicolo
authors.forename: Marisa H G
authors.initials: MH
authors.lastname: Medeiros
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Kowaltowski
mesh_terms: D050154:Adiposity; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D031204:Caloric Restriction / Q000379:methods*; D004038:Diet, Reducing / Q000379:methods*; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000032:analysis / Q000096:biosynthesis; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000096:biosynthesis; D009574:Nitro Compounds; D009765:Obesity / Q000178:diet therapy* / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D009574:Nitro Compounds; D019001:Nitric Oxide Synthase; D011972:Receptor, Insulin; D005947:Glucose