title: Knocking down amygdalar PTP1B in diet-induced obese rats improves insulin signaling/action, decreases adiposity and may alter anxiety behavior.
abstract: Protein tyrosine phosphatase 1B (PTP1B) has been extensively implicated in the regulation of body weight, food intake, and energy expenditure. The role of PTP1B appears to be cell and brain region dependent.
  
  
  
  Herein, we demonstrated that chronic high-fat feeding enhanced PTP1B expression in the central nucleus of the amygdala (CeA) of rats compared to rats on chow. Knocking down PTP1B with oligonucleotide antisense (ASO) decreased its expression and was sufficient to improve the anorexigenic effect of insulin through IR/Akt signaling in the CeA. ASO treatment reduces body weight, fat mass, serum leptin levels, and food intake and also increases energy expenditure, without altering ambulatory activity. These changes were explained, at least in part, by the improvement of insulin sensitivity in the CeA, decreasing NPY and enhancing oxytocin expression. There was a slight decline in fasting blood glucose and serum insulin levels possibly due to leanness in rats treated with ASO. Surprisingly, the elevated plus maze test revealed an anxiolytic behavior after reduction of PTP1B in the CeA.
  
  
  
  Thus, the present study highlights the deleterious role that the amygdalar PTP1B has on energy homeostasis in obesity states. The reduction of PTP1B in the CeA may be a strategy for the treatment of obesity, insulin resistance and anxiety disorders.
authors.affiliation: School of Applied Sciences, State University of Campinas, UNICAMP, Brazil.
authors.forename: Natalia Ferreira
authors.initials: NF
authors.lastname: Mendes
authors.affiliation: Department of Internal Medicine, State University of Campinas, UNICAMP, Brazil.
authors.forename: Gisele
authors.initials: G
authors.lastname: Castro
authors.affiliation: Department of Internal Medicine, State University of Campinas, UNICAMP, Brazil.
authors.forename: Dioze
authors.initials: D
authors.lastname: Guadagnini
authors.affiliation: Department of Internal Medicine, State University of Campinas, UNICAMP, Brazil.
authors.forename: Natalia
authors.initials: N
authors.lastname: Tobar
authors.affiliation: Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, USP, Brazil.
authors.forename: Susana Quiros
authors.initials: SQ
authors.lastname: Cognuck
authors.affiliation: Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, USP, Brazil.
authors.forename: Lucila Leico Kagohara
authors.initials: LL
authors.lastname: Elias
authors.affiliation: Department of Internal Medicine, State University of Campinas, UNICAMP, Brazil.
authors.forename: Patricia Aline
authors.initials: PA
authors.lastname: Boer
authors.affiliation: School of Applied Sciences, State University of Campinas, UNICAMP, Brazil; Department of Internal Medicine, State University of Campinas, UNICAMP, Brazil. Electronic address: pprada.fca@gmail.com.
authors.forename: Patricia Oliveira
authors.initials: PO
authors.lastname: Prada
mesh_terms: D050154:Adiposity / Q000235:genetics; D000679:Amygdala / Q000201:enzymology*; D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000235:genetics; D004032:Diet; D055785:Gene Knockdown Techniques / Q000379:methods; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000187:drug effects* / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D007328:Insulin; D016376:Oligonucleotides, Antisense; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516610:Ptpn1 protein, rat
keywords: Amygdala; Anxiety; Insulin; Obesity; PTP1B