Hexosamine biosynthetic pathway activity in leptin resistant sucrose-drinking rats

Ruth Babette Harris, John W. Apolzan

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 of. 1.5. 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 2. mg 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 3. h 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 30. min after leptin injection in leptin responsive animals, implying a complex interaction between activity of the HBP and leptin responsiveness.

Original languageEnglish (US)
Pages (from-to)208-218
Number of pages11
JournalPhysiology and Behavior
Volume138
DOIs
StatePublished - Jan 1 2015

Fingerprint

Hexosamines
Biosynthetic Pathways
Leptin
Drinking
Sucrose
Injections
Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
STAT3 Transcription Factor
Arcuate Nucleus of Hypothalamus
Third Ventricle
Glucosamine
Enzymes
Fructose
Intravenous Infusions
Hypothalamus
Proteins
Western Blotting
Immunohistochemistry
Phosphorylation
Glucose

Keywords

  • GFAT
  • Glucosamine
  • Hexosamine biosynthetic pathway
  • Hypothalamic pSTAT3
  • OGT

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Behavioral Neuroscience

Cite this

Hexosamine biosynthetic pathway activity in leptin resistant sucrose-drinking rats. / Harris, Ruth Babette; Apolzan, John W.

In: Physiology and Behavior, Vol. 138, 01.01.2015, p. 208-218.

Research output: Contribution to journalArticle

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