DTA

Digital Theses Archive

 

Tesi etd-09192017-144934

Type of thesis
Perfezionamento
Author
MISTO, ALESSANDRA
E-mail address
mistoalessandra@gmail.com
URN
etd-09192017-144934
Title
Interactions between mast cells-derived histamine and oleoylethanolamide control liver ketone body production.
Scientific disciplinary sector
BIO/14
Course
SCIENZE MEDICHE - Translational Medicine
Committee
relatore Prof. LIONETTI, VINCENZO
Keywords
  • fasting
  • histamine
  • ketone bodies
  • liver.
  • mast cells
  • Oleoylethanolamide
Exam session start date
;
Availability
parziale
Abstract
Mammalian metabolism adapts to nutrient insufficiency by simultaneously turning on lipolysis (release of fatty acids from adipose stores) and ketogenesis (conversion of fatty acids into ketone bodies). Fasting-induced ketogenesis occurs primarily in liver, but is controlled by a combination of systemic signals (such as the catabolic hormone glucagone) and liver-autonomous processes governed by peroxisome proliferator-activated receptor-α (PPAR-alpha). Here, we describe an unprecedented paracrine mechanism that regulates ketogenesis. Using genetic and pharmacological approaches, we show that fasting stimulates mast cells to secrete the biogenic amine, histamine, which enters the liver through the hepatic portal circulation, activates local H1 receptors, and triggers biosynthesis of the endogenous PPAR-alpha agonist oleoylethanolamide (OEA). Interventions that disable this sequence of reactions markedly impair ketogenesis, but do not affect lipolysis. The results reveal an unexpected role for histamine in the control of bioenergetics homeostasis, and suggest that dysfunctions in histamine-dependent OEA signaling might contribute to metabolic disease.
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