title: Lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFα) blunt the response of Neuropeptide Y/Agouti-related peptide (NPY/AgRP) glucose inhibited (GI) neurons to decreased glucose.
abstract: A population of Neuropeptide Y (NPY) neurons which co-express Agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus (ARC) are inhibited at physiological levels of brain glucose and activated when glucose levels decline (e.g. glucose-inhibited or GI neurons). Fasting enhances the activation of NPY/AgRP-GI neurons by low glucose. In the present study we tested the hypothesis that lipopolysaccharide (LPS) inhibits the enhanced activation of NPY/AgRP-GI neurons by low glucose following a fast. Mice which express green fluorescent protein (GFP) on their NPY promoter were used to identify NPY/AgRP neurons. Fasting for 24h and LPS injection decreased blood glucose levels. As we have found previously, fasting increased c-fos expression in NPY/AgRP neurons and increased the activation of NPY/AgRP-GI neurons by decreased glucose. As we predicted, LPS blunted these effects of fasting at the 24h time point. Moreover, the inflammatory cytokine tumor necrosis factor alpha (TNFα) blocked the activation of NPY/AgRP-GI neurons by decreased glucose. These data suggest that LPS and TNFα may alter glucose and energy homeostasis, in part, due to changes in the glucose sensitivity of NPY/AgRP neurons. Interestingly, our findings also suggest that NPY/AgRP-GI neurons use a distinct mechanism to sense changes in extracellular glucose as compared to our previous studies of GI neurons in the adjacent ventromedial hypothalamic nucleus.
authors.affiliation: Department of Pharmacology, Physiology & Neuroscience, New Jersey Medical School, Rutgers University, Newark, NJ, USA; Graduate School of the Biomedical Sciences, New Jersey Medical School, Rutgers University, Newark, NJ, USA.
authors.forename: Lihong
authors.initials: L
authors.lastname: Hao
authors.affiliation: Department of Pharmacology, Physiology & Neuroscience, New Jersey Medical School, Rutgers University, Newark, NJ, USA.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Sheng
authors.affiliation: Department of Pharmacology, Physiology & Neuroscience, New Jersey Medical School, Rutgers University, Newark, NJ, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Potian
authors.affiliation: Department of Pharmacology, Physiology & Neuroscience, New Jersey Medical School, Rutgers University, Newark, NJ, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Deak
authors.affiliation: Department of Pharmacology, Physiology & Neuroscience, New Jersey Medical School, Rutgers University, Newark, NJ, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Rohowsky-Kochan
authors.affiliation: Department of Pharmacology, Physiology & Neuroscience, New Jersey Medical School, Rutgers University, Newark, NJ, USA. Electronic address: routhvh@njms.rutgers.edu.
authors.forename: Vanessa H
authors.initials: VH
authors.lastname: Routh
mesh_terms: D054369:Agouti-Related Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D005215:Fasting; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D007031:Hypothalamus / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D008070:Lipopolysaccharides; D009478:Neuropeptide Y; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose
keywords: Anorexia; Fasting; GI neurons; LPS; NPY/AgRP neurons; TNFα