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Leucine and Omega‐3 Fatty Acids Regulate Cell Bioenergetics via mTOR
Author(s) -
Baum Jamie,
Shouse Stephanie,
Lassiter Kentu,
Bottje Walter,
Dridi Sami
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.742.16
Subject(s) - bioenergetics , ucp3 , mitochondrion , medicine , endocrinology , oxidative phosphorylation , biology , chemistry , microbiology and biotechnology , biochemistry , adipose tissue , brown adipose tissue , uncoupling protein
Obesity occurs when energy intake exceeds energy expenditure (EE). EE decreases with age, which increases obesity rates in older populations. This makes EE (e.g. cellular bioenergetics) an attractive target for treating obesity. Cellular bioenergetics occurs in mitochondria. Increases in muscle can also increase EE, possibly due to the large number of mitochondria. This study determined if 1)leucine (Leu) and ω‐3 fatty acids (O3) can alter cellular bioenergetics and improve mitochondria function in muscle cells, 2)this is an mTOR‐mediated process, and 3)age alters efficacy of treatment. Young(Y) and aged(A) C2C12 myotubes were serum and leu starved for 12 hr then treated with rapamycin or DMSO for 1 hr. Cells then received one of four physiological treatments: control, 0.5mM leu, 60μM EPA/240μM DHA, or leu+EPA/DHA for 1 hr. Cellular bioenergetics (measurement of mitochondrial function) was measured using an XF24 Flux Analyzer. Basal O 2 consumption rate (represents mitochondrial OXPHO linked to ATP synthesis was not different b/w Y and A, however O 2 consumption linked to proton leak was higher ( P <0.05) in A. Y had more mitochondria than A. A were more responsive to nutrients and rapamycin inhibited both treatments, suggesting that Leu and O3 act via mTOR to alter mitochondrial function. NRF1 was higher ( P <0.05) in A and ANT1, UCP3, SIRT1 and PGC1a were higher ( P <0.05) in Y. SIRT1, ANT1 and NRF1 were increased with rapamycin ( P <0.05). PGC1a was increased ( P <0.05) with O3 and UCP was increased ( P <0.05) with Leu and O3. Taken together, these data suggest that both Leu and O3 regulate cell bioenergetics via mTOR in Y and A. Funded by AR Biosciences Inst. and UAMS Pepper Center Pilot Grant AG028718.