title: Hypothalamic inflammation without astrogliosis in response to high sucrose intake is modulated by neonatal nutrition in male rats.
abstract: Hypothalamic inflammation and gliosis are proposed to participate in the pathogenesis of high-fat diet-induced obesity. Because other factors and nutrients also induce weight gain and adiposity, we analyzed the inflammatory and glial responses to a sucrose (S)-enriched diet. Neonatal overnutrition (NON) exacerbates weight gain in response to metabolic challenges; thus, we compared the inflammatory response of male Wistar rats with NON (4 pups/litter) and controls (12 pups/litter) to increased S intake. At weaning rats received water or a 33% sucrose solution and normal chow ad libitum for 2 months. Sucrose increased serum IL-1β and -6 and hypothalamic IL-6 mRNA levels in NON and TNFα mRNA levels in control and NON rats, whereas NON alone had no effect. The astrocyte marker glial fibrillary acidic protein was increased by NON but decreased by S. This was associated with hypothalamic nuclei specific changes in glial fibrillary acidic protein-positive cell number and morphology. Sucrose increased the number of microglia and phosphorylation of inhibitor of -κB and c-Jun N-terminal kinase in control but not NON rats, with no effect on microglia activation markers. Proteins highly expressed in astrocytes (glutamate, glucose, and lactate transporters) were increased by NON but not S, with no increase in vimentin expression in astrocytes, further suggesting that S-induced adiposity is not associated with hypothalamic astrogliosis. Hence, activation of hypothalamic inflammatory processes and gliosis depend not only on weight gain but also on the diet inducing this weight gain and the early nutritional status. These diverse inflammatory processes could indicate a differential disposition to obesity-induced pathologies.
authors.affiliation: Hospital Infantil Universitario Niño Jesús, Department of Endocrinology, Instituto de Investigación La Princesa, 28009 Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Fuente-Martín
authors.forename: Cristina
authors.initials: C
authors.lastname: García-Cáceres
authors.forename: Francisca
authors.initials: F
authors.lastname: Díaz
authors.forename: Pilar
authors.initials: P
authors.lastname: Argente-Arizón
authors.forename: Miram
authors.initials: M
authors.lastname: Granado
authors.forename: Vicente
authors.initials: V
authors.lastname: Barrios
authors.forename: Jesús
authors.initials: J
authors.lastname: Argente
authors.forename: Julie A
authors.initials: JA
authors.lastname: Chowen
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D015153:Blotting, Western; D005911:Gliosis / Q000139:chemically induced*; D007031:Hypothalamus / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced*; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008297:Male; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects; D051381:Rats; D013395:Sucrose / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D015430:Weight Gain / Q000187:drug effects
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D013395:Sucrose