Activation of hypothalamic NPY, AgRP, MC4R, AND IL-6 mRNA levels in young Lewis rats with early-life diet-induced obesity
Language English Country Germany Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19817504
Knihovny.cz E-resources
- MeSH
- Adiponectin blood MeSH
- Adiposity MeSH
- Agouti-Related Protein genetics metabolism MeSH
- Analysis of Variance MeSH
- Adipose Tissue, White cytology MeSH
- Adipocytes, White MeSH
- Dietary Fats administration & dosage MeSH
- Energy Intake MeSH
- Gene Expression MeSH
- Ghrelin blood MeSH
- Interleukin-6 genetics metabolism MeSH
- Insulin blood MeSH
- Rats MeSH
- Leptin blood MeSH
- RNA, Messenger metabolism MeSH
- Neuropeptide Y genetics metabolism MeSH
- Nicotinamide Phosphoribosyltransferase blood MeSH
- Arcuate Nucleus of Hypothalamus metabolism MeSH
- Paraventricular Hypothalamic Nucleus metabolism MeSH
- Obesity genetics metabolism MeSH
- Area Under Curve MeSH
- Glucose Intolerance MeSH
- Rats, Inbred Lew MeSH
- Receptor, Melanocortin, Type 4 genetics metabolism MeSH
- Appetite Regulation physiology MeSH
- Aging MeSH
- Feeding Behavior MeSH
- Body Weight MeSH
- Cell Size MeSH
- Litter Size MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adiponectin MeSH
- Agouti-Related Protein MeSH
- Dietary Fats MeSH
- Ghrelin MeSH
- Interleukin-6 MeSH
- Insulin MeSH
- Leptin MeSH
- RNA, Messenger MeSH
- Neuropeptide Y MeSH
- Nicotinamide Phosphoribosyltransferase MeSH
- Receptor, Melanocortin, Type 4 MeSH
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. CONCLUSION: 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.
