title: Hepatic autophagy contributes to the metabolic response to dietary protein restriction.
abstract: Autophagy is an essential cellular response which acts to release stored cellular substrates during nutrient restriction, and particularly plays a key role in the cellular response to amino acid restriction. However, there has been limited work testing whether the induction of autophagy is required for adaptive metabolic responses to dietary protein restriction in the whole animal. Here, we found that moderate dietary protein restriction led to a series of metabolic changes in rats, including increases in food intake and energy expenditure, the downregulation of hepatic fatty acid synthesis gene expression and reduced markers of hepatic mitochondrial number. Importantly, these effects were also associated with an induction of hepatic autophagy. To determine if the induction of autophagy contributes to these metabolic effects, we tested the metabolic response to dietary protein restriction in BCL2-AAA mice, which bear a genetic mutation that impairs autophagy induction. Interestingly, BCL2-AAA mice exhibit exaggerated responses in terms of both food intake and energy expenditure, whereas the effects of protein restriction on hepatic metabolism were significantly blunted. These data demonstrate that restriction of dietary protein is sufficient to trigger hepatic autophagy, and that disruption of autophagy significantly alters both hepatic and whole animal metabolic response to dietary protein restriction.
authors.affiliation: Neurosignaling, Imaging and Culture Core, Pennington Biomedical Research Center, Baton Rouge, LA 70808.
authors.forename: Tara M
authors.initials: TM
authors.lastname: Henagan
authors.affiliation: Neurosignaling, Imaging and Culture Core, Pennington Biomedical Research Center, Baton Rouge, LA 70808.
authors.forename: Thomas
authors.initials: T
authors.lastname: Laeger
authors.affiliation: Neurosignaling, Imaging and Culture Core, Pennington Biomedical Research Center, Baton Rouge, LA 70808.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Navard
authors.affiliation: Neurosignaling, Imaging and Culture Core, Pennington Biomedical Research Center, Baton Rouge, LA 70808.
authors.forename: Diana
authors.initials: D
authors.lastname: Albarado
authors.affiliation: Skeletal Muscle Metabolism, Imaging and Culture Core, Pennington Biomedical Research Center, Baton Rouge, LA 70808.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Noland
authors.affiliation: Oxidative Stress and Disease, Imaging and Culture Core, Pennington Biomedical Research Center, Baton Rouge, LA 70808.
authors.forename: Krisztian
authors.initials: K
authors.lastname: Stadler
authors.affiliation: Matrix Biology, Imaging and Culture Core, Pennington Biomedical Research Center, Baton Rouge, LA 70808.
authors.forename: Carrie M
authors.initials: CM
authors.lastname: Elks
authors.affiliation: Cell Biology, Imaging and Culture Core, Pennington Biomedical Research Center, Baton Rouge, LA 70808.
authors.forename: David
authors.initials: D
authors.lastname: Burk
authors.affiliation: Neurosignaling, Imaging and Culture Core, Pennington Biomedical Research Center, Baton Rouge, LA 70808. Electronic address: christopher.morrison@pbrc.edu.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Morrison
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D018753:Diet, Protein-Restricted; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D009154:Mutation; D011488:Protein Deficiency / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Amino acids; Autophagy; Energy expenditure; Food intake; Metabolism