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The role of liver fructose-1,6-bisphosphatase in regulating appetite and adiposity.

Abstract
Liver fructose-1,6-bisphosphatase (FBPase) is a regulatory enzyme in gluconeogenesis that is elevated by obesity and dietary fat intake. Whether FBPase functions only to regulate glucose or has other metabolic consequences is not clear; therefore, the aim of this study was to determine the importance of liver FBPase in body weight regulation. To this end we performed comprehensive physiologic and biochemical assessments of energy balance in liver-specific transgenic FBPase mice and negative control littermates of both sexes. In addition, hepatic branch vagotomies and pharmacologic inhibition studies were performed to confirm the role of FBPase. Compared with negative littermates, liver-specific FBPase transgenic mice had 50% less adiposity and ate 15% less food but did not have altered energy expenditure. The reduced food consumption was associated with increased circulating leptin and cholecystokinin, elevated fatty acid oxidation, and 3-β-hydroxybutyrate ketone levels, and reduced appetite-stimulating neuropeptides, neuropeptide Y and Agouti-related peptide. Hepatic branch vagotomy and direct pharmacologic inhibition of FBPase in transgenic mice both returned food intake and body weight to the negative littermates. This is the first study to identify liver FBPase as a previously unknown regulator of appetite and adiposity and describes a novel process by which the liver participates in body weight regulation.
AuthorsSherley Visinoni, Nurul Fathiah Izzati Khalid, Christos N Joannides, Arthur Shulkes, Mildred Yim, Jon Whitehead, Tony Tiganis, Benjamin J Lamont, Jenny M Favaloro, Joseph Proietto, Sofianos Andrikopoulos, Barbara C Fam
JournalDiabetes (Diabetes) Vol. 61 Issue 5 Pg. 1122-32 (May 2012) ISSN: 1939-327X [Electronic] United States
PMID22517657 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Agouti-Related Protein
  • Agrp protein, mouse
  • Fatty Acids
  • Hydroxybutyrates
  • Ketone Bodies
  • Leptin
  • Neuropeptide Y
  • Peptide Fragments
  • neuropeptide Y (1-30)
  • Cholecystokinin
  • Fructose-Bisphosphatase
Topics
  • Adiposity (genetics, physiology)
  • Agouti-Related Protein (genetics, metabolism)
  • Animals
  • Appetite (genetics, physiology)
  • Cholecystokinin (metabolism)
  • Dose-Response Relationship, Drug
  • Eating
  • Energy Metabolism
  • Fatty Acids (metabolism)
  • Female
  • Fructose-Bisphosphatase (antagonists & inhibitors, genetics, metabolism)
  • Gene Expression Regulation (drug effects, physiology)
  • Humans
  • Hydroxybutyrates
  • Ketone Bodies
  • Leptin (metabolism)
  • Liver (enzymology)
  • Male
  • Mice
  • Mice, Transgenic
  • Neuropeptide Y (genetics, metabolism)
  • Oxidation-Reduction
  • Peptide Fragments (genetics, metabolism)

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