Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states.
Dietary methionine restriction (MR) is a mimetic of chronic dietary restriction (DR) in the sense that MR increases rodent longevity, but without food restriction. We report here that MR also persistently increases total energy expenditure (EE) and limits fat deposition despite increasing weight-specific food consumption. In Fischer 344 (F344) rats consuming control or MR diets for 3, 9, and 20 mo, mean EE was 1.5-fold higher in MR vs. control rats, primarily due to higher EE during the night at all ages. The day-to-night transition produced a twofold higher heat increment of feeding (3.0 degrees C vs. 1.5 degrees C) in MR vs. controls and an exaggerated increase in respiratory quotient (RQ) to values greater than 1, indicative of the interconversion of glucose to lipid by de novo lipogenesis. The simultaneous inhibition of glucose utilization and shift to fat oxidation during the day was also more complete in MR (RQ approximately 0.75) vs. controls (RQ approximately 0.85). Dietary MR produced a rapid and persistent increase in uncoupling protein 1 expression in brown (BAT) and white adipose tissue (WAT) in conjunction with decreased leptin and increased adiponectin levels in serum, suggesting that remodeling of the metabolic and endocrine function of adipose tissue may have an important role in the overall increase in EE. We conclude that the hyperphagic response to dietary MR is matched to a coordinated increase in uncoupled respiration, suggesting the engagement of a nutrient-sensing mechanism, which compensates for limited methionine through integrated effects on energy homeostasis.
Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
Barbara E
BE
Hasek
Laura K
LK
Stewart
Tara M
TM
Henagan
Anik
A
Boudreau
Natalie R
NR
Lenard
Corey
C
Black
Jeho
J
Shin
Peter
P
Huypens
Virginia L
VL
Malloy
Eric P
EP
Plaisance
Rozlyn A
RA
Krajcik
Norman
N
Orentreich
Thomas W
TW
Gettys
D000273:Adipose Tissue; D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology; D002940:Circadian Rhythm; D004032:Diet; D004041:Dietary Fats; D004734:Energy Metabolism / Q000187:drug effects*; D005508:Food Deprivation; D005786:Gene Expression Regulation / Q000502:physiology; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000172:deficiency*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009043:Motor Activity; D009765:Obesity; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains; D000071256:Uncoupling Protein 1
D004041:Dietary Fats; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; D008715:Methionine