title: High-fructose diet leads to visceral adiposity and hypothalamic leptin resistance in male rats--do glucocorticoids play a role?
abstract: Fructose overconsumption has been involved in the genesis and progression of the metabolic syndrome. Hypothalamus and adipose tissue, major organs for control of food intake and energy metabolism, play crucial roles in metabolic homeostasis. We hypothesized that glucocorticoid signaling mediates the effects of a fructose-enriched diet on visceral adiposity by acting on neuropeptide Y (NPY) in the hypothalamus and altering adipogenic transcription factors in the visceral adipose tissue. We analyzed the effects of 9-week consumption of 60% fructose solution on dyslipidemia, insulin and leptin sensitivity, and adipose tissue histology in male Wistar rats. Glucocorticoid signaling was assessed in both hypothalamus and visceral adipose tissue, while the levels of peroxisome-proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein-1 (SREBP-1) and lipin-1, together with the levels of their target genes expression, were analyzed in the visceral adipose tissue. The results showed that long-term consumption of highly concentrated liquid fructose led to the development of visceral adiposity, elevated triglycerides and hypothalamic leptin resistance accompanied by stimulated glucocorticoid signaling and NPY mRNA elevation. Results from adipose tissue implied that fructose consumption shifted the balance between glucocorticoid receptor and adipogenic transcriptional factors (PPARγ, SREBP-1 and lipin-1) in favor of adipogenesis judged by distinctly separated populations of small adipocytes observed in this tissue. In summary, we propose that high-fructose-diet-induced alterations of glucocorticoid signaling in both hypothalamus and adipose tissue result in enhanced adipogenesis, possibly serving as an adaptation to energy excess in order to limit deposition of fat in nonadipose tissues.
authors.affiliation: Department of Biochemistry, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., 11000 Belgrade, Serbia.
authors.forename: Biljana N
authors.initials: BN
authors.lastname: Bursać
authors.affiliation: Department of Biochemistry, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., 11000 Belgrade, Serbia.
authors.forename: Ana D
authors.initials: AD
authors.lastname: Vasiljević
authors.affiliation: Department of Cytology, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., 11000 Belgrade, Serbia.
authors.forename: Nataša M
authors.initials: NM
authors.lastname: Nestorović
authors.affiliation: Department of Biochemistry, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., 11000 Belgrade, Serbia.
authors.forename: Nataša A
authors.initials: NA
authors.lastname: Veličković
authors.affiliation: Department of Biochemistry, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., 11000 Belgrade, Serbia.
authors.forename: Danijela D
authors.initials: DD
authors.lastname: Vojnović Milutinović
authors.affiliation: Department of Biochemistry, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., 11000 Belgrade, Serbia.
authors.forename: Gordana M
authors.initials: GM
authors.lastname: Matić
authors.affiliation: Department of Biochemistry, Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 Despot Stefan Blvd., 11000 Belgrade, Serbia. Electronic address: djordjevica@ibiss.bg.ac.rs.
authors.forename: Ana D
authors.initials: AD
authors.lastname: Djordjevic
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D004032:Diet; D005632:Fructose / Q000009:adverse effects*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020738:Leptin / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020738:Leptin; C530902:Lpin1 protein, rat; D009478:Neuropeptide Y; D009687:Nuclear Proteins; D047495:PPAR gamma; D011965:Receptors, Glucocorticoid; D054411:Receptors, Leptin; C491410:Socs3 protein, rat; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D005632:Fructose
keywords: Adipogenesis; Fructose; Glucocorticoids; Hypothalamus; Leptin; Visceral adipose tissue