Cellular and molecular remodeling of inguinal adipose tissue mitochondria by dietary methionine restriction.
Dietary methionine restriction (MR) produces a coordinated series of biochemical and physiological responses that improve biomarkers of metabolic health, increase energy expenditure, limit fat accretion and improve overall insulin sensitivity. Inguinal white adipose tissue (IWAT) is a primary target and site of action where the diet initiates transcriptional programs linked to enhancing both synthesis and oxidation of lipid. Using a combination of ex vivo approaches to assess dietary effects on cell morphology and function, we report that dietary MR produced a fourfold increase in multilocular, UCP1-expressing cells within this depot in conjunction with significant increases in mitochondrial content, size and cristae density. Dietary MR increased expression of multiple enzymes within the citric acid cycle, as well as respiratory complexes I, II and III. The physiological significance of these responses, evaluated in isolated mitochondria by high-resolution respirometry, was a significant increase in respiratory capacity measured using multiple substrates. The morphological, transcriptional and biochemical remodeling of IWAT mitochondria enhances the synthetic and oxidative capacity of this tissue and collectively underlies its expanded role as a significant contributor to the overall increase in metabolic flexibility and uncoupled respiration produced by the diet.
Nutrient Sensing and Adipocyte Signaling Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808.
Yuvraj N
YN
Patil
Nutrient Sensing and Adipocyte Signaling Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808.
Kelly N
KN
Dille
Nutrient Sensing and Adipocyte Signaling Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808.
David H
DH
Burk
Nutrient Sensing and Adipocyte Signaling Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808.
Cory C
CC
Cortez
Nutrient Sensing and Adipocyte Signaling Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808. Electronic address: Thomas.Gettys@pbrc.edu.
Thomas W
TW
Gettys
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D003600:Cytosol / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D000071256:Uncoupling Protein 1 / Q000378:metabolism
D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D008715:Methionine
Adipocyte remodeling; Dietary restriction; Essential amino acid; Mitochondrial ultrastructure; Respirometry