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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Harris, Ruth B. S. Apolzan, John W. |
| Description | Author Affiliation: Harris RB ( Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, United States. Electronic address: ruharris@gru.edu.); Apolzan JW ( Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, United States.) |
| Abstract | Rats offered 30% sucrose solution in addition to chow and water become leptin resistant therefore we investigated the effect of sucrose solution consumption on leptin signaling. In Experiment 1 rats were resistant to 3rd ventricle injections of1.5 µg leptin after 36 days of sucrose and western blot indicated that resistance was associated with increased basal levels of signal transducer and activator of transcription 3 phosphorylation (pSTAT3). In Experiment 2 rats were resistant to a peripheral injection of 2mg leptin/kg after 26 days of sucrose. Immunohistochemistry indicated that increased basal pSTAT3 was limited to the medial and lateral arcuate nucleus of the hypothalamus. Increased availability of glucose and fructose can stimulate the hexosamine biosynthetic pathway (HBP) which O-GlcNAc-modifies proteins. This has the potential to change protein bioactivity. We tested whether this pathway could account for the leptin resistance. There was no increase in the expression of HBP enzymes in tissues from sucrose rats in Experiment 1, however, direct activation of the HBP with a 3h intravenous infusion of 30 µmol/kg/min glucosamine significantly increased hypothalamic pSTAT3. Although sucrose consumption and activation of the HBP both increase hypothalamic pSTAT3 experiments described here did not provide evidence of a direct link between sucrose consumption, HBP activity and leptin resistance. Unexpectedly, we found that the HBP enzyme glutamine fructose-6-phosphate amidotransferase (GFAT) in liver and O-GlcNAcase in hypothalamus were increased 30min after leptin injection in leptin responsive animals, implying a complex interaction between activity of the HBP and leptin responsiveness. |
| File Format | HTM / HTML |
| ISSN | 00319384 |
| e-ISSN | 1873507X |
| DOI | 10.1016/j.physbeh.2014.09.016 |
| Journal | Physiology & Behavior |
| Volume Number | 138 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2015-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Research Support, N.i.h., Extramural Glucosamine Phosphorylation Glutamine-fructose-6-phosphate Transaminase (isomerizing) Liver Acetylglucosamine Rhombencephalon Hypothalamus Blood N-acetylglucosaminyltransferases Discipline Physiology Physiology Dietary Sucrose Rats, Sprague-dawley Blood Glucose Administration & Dosage Biosynthetic Pathways Pharmacology Metabolism Stat3 Transcription Factor Drug Effects Insulin Animals Leptin Hexosamines Central Nervous System Agents Enzymology Discipline Behavioral Neuroscience |
| Content Type | Text |
| Resource Type | Article |
| Subject | Experimental and Cognitive Psychology Behavioral Neuroscience |
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