title: Activation of hypothalamic NPY, AgRP, MC4R, AND IL-6 mRNA levels in young Lewis rats with early-life diet-induced obesity.
abstract: OBJECTIVE
  Obesity represents a low-grade inflammatory disease and appears a risk factor for insulin resistance, but little is known on whether this may contribute to the development of autoimmune inflammatory diseases. The aim of this work was to study the early-life diet-induced obesity in Lewis rats which are known to be highly susceptible to autoimmunity.
  
  
  METHODS
  Obesity was induced by reduced litter size (4 pups per litter) followed by high-fat diet (SHF rats). Control rats (8 pups per litter) were fed with standard diet (CN rats). Oral glucose tolerance test (3 g glucose per kg b.w.) was performed by intra-gastric tube in conscious rats after 12 h fast. Adipocyte size was assessed by light microscope after collagenase digestion. Hypothalamic arcuate (ARC) and paraventricular nuclei (PVN) were isolated by the punching technique. Target mRNAs were quantified by real-time PCR with the use of TaqMan probes and primers. Serum hormones (leptin, ghrelin, adiponectin, visfatin and insulin) were assayed by specific RIAs .
  
  
  RESULTS
  During the experimental period SHF rats had the same body weight gain and caloric intake as CN rats. At the age of 8 weeks SHF rats showed increased epididymal fat mass and adipocyte volume, impaired glucose tolerance, normal basal fasting insulin, visfatin, and ghrelin level, but decreased adiponectin and high leptin level. In the ARC, the SHF rats showed increased expression of mRNA for orexigenic neuropeptide Y (NPY), agouti-related protein (AgRP) and anorexigenic pro-inflammatory cytokine IL-6. In the PVN, the SHF rats showed increased expression of mRNA for anorexigenic melanocortin 4 receptor (MC4R) and IL-6.
  
  
  CONCLUSIONS
  Overexpression of orexigenic NPY and AgRP in the ARC indicates leptin resistance in SHF rats. The increased expression of MC4R in PVN points to the activation of melanocortin anorexigenic system which, along with increased hypothalamic IL-6, might prevent the animals from overfeeding. Higher adiposity in these rats results from the high fat-diet composition and not from increased caloric intake. Furthermore, enhanced leptin production appears the main factor indicating the predisposition to autoimmunity in these overfed rats.
authors.affiliation: Department of Normal, Pathological and Clinical Physiology, Third Faculty of Medicine, Charles University in Prague, Ke Karlovu 4, 120 00 Prague, Czech Republic. andrea.stofkova@lf3.cuni.cz
authors.forename: A
authors.initials: A
authors.lastname: Stofkova
authors.forename: M
authors.initials: M
authors.lastname: Skurlova
authors.forename: A
authors.initials: A
authors.lastname: Kiss
authors.forename: B
authors.initials: B
authors.lastname: Zelezna
authors.forename: S
authors.initials: S
authors.lastname: Zorad
authors.forename: J
authors.initials: J
authors.lastname: Jurcovicova
mesh_terms: D052438:Adipocytes, White; D052242:Adiponectin / Q000097:blood; D052436:Adipose Tissue, White / Q000166:cytology; D050154:Adiposity; D000375:Aging; D054369:Agouti-Related Protein / Q000235:genetics* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001069:Appetite Regulation / Q000502:physiology; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D019540:Area Under Curve; D001835:Body Weight; D048429:Cell Size; D004041:Dietary Fats / Q000008:administration & dosage; D002149:Energy Intake; D005247:Feeding Behavior; D015870:Gene Expression; D054439:Ghrelin / Q000097:blood; D018149:Glucose Intolerance; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008098:Litter Size; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics* / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics* / Q000378:metabolism
chemical_list: D052242:Adiponectin; D054369:Agouti-Related Protein; D004041:Dietary Fats; D054439:Ghrelin; D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D009478:Neuropeptide Y; D012333:RNA, Messenger; D044105:Receptor, Melanocortin, Type 4; D054409:Nicotinamide Phosphoribosyltransferase