Lipid Droplet-Derived Monounsaturated Fatty Acids Traffic via PLIN5 to Allosterically Activate SIRT1

Charles P. Najt; Salmaan A. Khan; Timothy D. Heden; Bruce A. Witthuhn; Minervo Perez; Jason L. Heier; Linnea E. Mead; Mallory P. Franklin; Kenneth K. Karanja; Mark J. Graham; Mara T. Mashek; David A. Bernlohr; Laurie Parker; Lisa S. Chow; Douglas G. Mashek

doi:10.1016/j.molcel.2019.12.003

Lipid Droplet-Derived Monounsaturated Fatty Acids Traffic via PLIN5 to Allosterically Activate SIRT1

Charles P. Najt, Salmaan A. Khan, Timothy D. Heden, Bruce A. Witthuhn, Minervo Perez, Jason L. Heier, Linnea E. Mead, Mallory P. Franklin, Kenneth K. Karanja, Mark J. Graham, Mara T. Mashek, David A. Bernlohr, Laurie Parker, Lisa S. Chow, Douglas G. Mashek

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Najt et al. identify the first-known endogenous allosteric modulator of SIRT1 and characterize a lipid droplet-nuclear signaling axis that underlies the known metabolic benefits of monounsaturated fatty acids and PLIN5.

Original language	English (US)
Pages (from-to)	810-824.e8
Journal	Molecular Cell
Volume	77
Issue number	4
DOIs	https://doi.org/10.1016/j.molcel.2019.12.003
State	Published - Feb 20 2020

Bibliographical note

Funding Information:
We would like to thank Candace Guerrero, Mitchell Fuller, Michael Autry, Colleen Forster, and Guillermo Marques for their technical assistance. We thank the University of Minnesota Imaging Center, Center for Mass Spectrometry and Proteomics, Clinical and Translational Science Biospecimen Support Center, and the Biophysical Technology Center for providing instrumentation and expertise. We thank Eduarado Chini for help with initial SIRT1 assays, Barbara Atshaves for antibodies and protocols, and Ann Hertzel for scientific discussions. Funding was provided for C.P.N. (NIH: T32DK007203 and T32AG029796), T.D.H. (NIH: F32DK109556 and L30DK110338), M.P. (NIH: R01CA182543-S1), M.P.F. (NIH: T32DK083250), D.A.B. (NIH: R01DK053189 and the University of Minnesota E-0917-2), L.S.C. (NIH: R01DK098203), and D.G.M. (NIH: R01AG055452, R01DK108790, R01DK114401, and the American Diabetes Association: 1-16-IBS-203). D.G.M. C.P.N. T.D.H. L.S.C. and S.A.K. conception and design of research; C.P.N. T.D.H. S.A.K. M.P. J.L.H. L.E.M. M.P.K. K.K.K. and M.T.M. performed experiments; C.P.N. T.D.H. S.A.K. D.G.M. and B.A.W. analyzed data; C.P.N. T.D.H. L.S.C. D.A.B. and D.G.M. interpreted results of experiments; C.P.N. S.A.K. and D.G.M. prepared figures; C.P.N. and D.G.M. drafted manuscript; M.J.G. J.L.H. and L.P. contributed materials and regents necessary for completion of studies; C.P.N. D.G.M. D.A.B. L.S.C. T.D.H. and B.A.W. edited and revised manuscript; C.P.N. S.A.K. T.D.H. B.A.W. M.P. J.L.H, L.E.M. M.P.F. K.K.K. M.J.G. M.T.M. D.A.B. L.P. L.S.C. and D.G.M. approved final version of manuscript. The authors declare no competing interests.

Funding Information:
We would like to thank Candace Guerrero, Mitchell Fuller, Michael Autry, Colleen Forster, and Guillermo Marques for their technical assistance. We thank the University of Minnesota Imaging Center, Center for Mass Spectrometry and Proteomics, Clinical and Translational Science Biospecimen Support Center, and the Biophysical Technology Center for providing instrumentation and expertise. We thank Eduarado Chini for help with initial SIRT1 assays, Barbara Atshaves for antibodies and protocols, and Ann Hertzel for scientific discussions. Funding was provided for C.P.N. ( NIH : T32DK007203 and T32AG029796 ), T.D.H. ( NIH : F32DK109556 and L30DK110338 ), M.P. ( NIH : R01CA182543-S1 ), M.P.F. ( NIH : T32DK083250 ), D.A.B. ( NIH : R01DK053189 and the University of Minnesota E-0917-2 ), L.S.C. ( NIH : R01DK098203 ), and D.G.M. ( NIH : R01AG055452 , R01DK108790 , R01DK114401 , and the American Diabetes Association : 1-16-IBS-203 ).

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

ATGL
fatty acids
lipid droplets
lipolysis
MUFA
olive oil
oxidative metabolism
PGC-1α
PLIN5
SIRT1

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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Najt, C. P., Khan, S. A., Heden, T. D., Witthuhn, B. A., Perez, M., Heier, J. L., Mead, L. E., Franklin, M. P., Karanja, K. K., Graham, M. J., Mashek, M. T., Bernlohr, D. A., Parker, L., Chow, L. S., & Mashek, D. G. (2020). Lipid Droplet-Derived Monounsaturated Fatty Acids Traffic via PLIN5 to Allosterically Activate SIRT1. Molecular Cell, 77(4), 810-824.e8. https://doi.org/10.1016/j.molcel.2019.12.003

Lipid Droplet-Derived Monounsaturated Fatty Acids Traffic via PLIN5 to Allosterically Activate SIRT1. / Najt, Charles P.; Khan, Salmaan A.; Heden, Timothy D.; Witthuhn, Bruce A.; Perez, Minervo; Heier, Jason L.; Mead, Linnea E.; Franklin, Mallory P.; Karanja, Kenneth K.; Graham, Mark J.; Mashek, Mara T.; Bernlohr, David A.; Parker, Laurie ; Chow, Lisa S.; Mashek, Douglas G.

In: Molecular Cell, Vol. 77, No. 4, 20.02.2020, p. 810-824.e8.

Research output: Contribution to journal › Article › peer-review

Najt, CP, Khan, SA, Heden, TD , Witthuhn, BA, Perez, M, Heier, JL, Mead, LE, Franklin, MP, Karanja, KK, Graham, MJ, Mashek, MT , Bernlohr, DA , Parker, L , Chow, LS & Mashek, DG 2020, 'Lipid Droplet-Derived Monounsaturated Fatty Acids Traffic via PLIN5 to Allosterically Activate SIRT1', Molecular Cell, vol. 77, no. 4, pp. 810-824.e8. https://doi.org/10.1016/j.molcel.2019.12.003

Najt, Charles P. ; Khan, Salmaan A. ; Heden, Timothy D. ; Witthuhn, Bruce A. ; Perez, Minervo ; Heier, Jason L. ; Mead, Linnea E. ; Franklin, Mallory P. ; Karanja, Kenneth K. ; Graham, Mark J. ; Mashek, Mara T. ; Bernlohr, David A. ; Parker, Laurie ; Chow, Lisa S. ; Mashek, Douglas G. / Lipid Droplet-Derived Monounsaturated Fatty Acids Traffic via PLIN5 to Allosterically Activate SIRT1. In: Molecular Cell. 2020 ; Vol. 77, No. 4. pp. 810-824.e8.

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title = "Lipid Droplet-Derived Monounsaturated Fatty Acids Traffic via PLIN5 to Allosterically Activate SIRT1",

abstract = "Najt et al. identify the first-known endogenous allosteric modulator of SIRT1 and characterize a lipid droplet-nuclear signaling axis that underlies the known metabolic benefits of monounsaturated fatty acids and PLIN5.",

keywords = "ATGL, fatty acids, lipid droplets, lipolysis, MUFA, olive oil, oxidative metabolism, PGC-1α, PLIN5, SIRT1",

author = "Najt, {Charles P.} and Khan, {Salmaan A.} and Heden, {Timothy D.} and Witthuhn, {Bruce A.} and Minervo Perez and Heier, {Jason L.} and Mead, {Linnea E.} and Franklin, {Mallory P.} and Karanja, {Kenneth K.} and Graham, {Mark J.} and Mashek, {Mara T.} and Bernlohr, {David A.} and Laurie Parker and Chow, {Lisa S.} and Mashek, {Douglas G.}",

note = "Funding Information: We would like to thank Candace Guerrero, Mitchell Fuller, Michael Autry, Colleen Forster, and Guillermo Marques for their technical assistance. We thank the University of Minnesota Imaging Center, Center for Mass Spectrometry and Proteomics, Clinical and Translational Science Biospecimen Support Center, and the Biophysical Technology Center for providing instrumentation and expertise. We thank Eduarado Chini for help with initial SIRT1 assays, Barbara Atshaves for antibodies and protocols, and Ann Hertzel for scientific discussions. Funding was provided for C.P.N. (NIH: T32DK007203 and T32AG029796), T.D.H. (NIH: F32DK109556 and L30DK110338), M.P. (NIH: R01CA182543-S1), M.P.F. (NIH: T32DK083250), D.A.B. (NIH: R01DK053189 and the University of Minnesota E-0917-2), L.S.C. (NIH: R01DK098203), and D.G.M. (NIH: R01AG055452, R01DK108790, R01DK114401, and the American Diabetes Association: 1-16-IBS-203). D.G.M. C.P.N. T.D.H. L.S.C. and S.A.K. conception and design of research; C.P.N. T.D.H. S.A.K. M.P. J.L.H. L.E.M. M.P.K. K.K.K. and M.T.M. performed experiments; C.P.N. T.D.H. S.A.K. D.G.M. and B.A.W. analyzed data; C.P.N. T.D.H. L.S.C. D.A.B. and D.G.M. interpreted results of experiments; C.P.N. S.A.K. and D.G.M. prepared figures; C.P.N. and D.G.M. drafted manuscript; M.J.G. J.L.H. and L.P. contributed materials and regents necessary for completion of studies; C.P.N. D.G.M. D.A.B. L.S.C. T.D.H. and B.A.W. edited and revised manuscript; C.P.N. S.A.K. T.D.H. B.A.W. M.P. J.L.H, L.E.M. M.P.F. K.K.K. M.J.G. M.T.M. D.A.B. L.P. L.S.C. and D.G.M. approved final version of manuscript. The authors declare no competing interests. Funding Information: We would like to thank Candace Guerrero, Mitchell Fuller, Michael Autry, Colleen Forster, and Guillermo Marques for their technical assistance. We thank the University of Minnesota Imaging Center, Center for Mass Spectrometry and Proteomics, Clinical and Translational Science Biospecimen Support Center, and the Biophysical Technology Center for providing instrumentation and expertise. We thank Eduarado Chini for help with initial SIRT1 assays, Barbara Atshaves for antibodies and protocols, and Ann Hertzel for scientific discussions. Funding was provided for C.P.N. ( NIH : T32DK007203 and T32AG029796 ), T.D.H. ( NIH : F32DK109556 and L30DK110338 ), M.P. ( NIH : R01CA182543-S1 ), M.P.F. ( NIH : T32DK083250 ), D.A.B. ( NIH : R01DK053189 and the University of Minnesota E-0917-2 ), L.S.C. ( NIH : R01DK098203 ), and D.G.M. ( NIH : R01AG055452 , R01DK108790 , R01DK114401 , and the American Diabetes Association : 1-16-IBS-203 ). Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2020",

month = feb,

day = "20",

doi = "10.1016/j.molcel.2019.12.003",

language = "English (US)",

volume = "77",

pages = "810--824.e8",

journal = "Molecular Cell",

issn = "1097-2765",

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T1 - Lipid Droplet-Derived Monounsaturated Fatty Acids Traffic via PLIN5 to Allosterically Activate SIRT1

AU - Najt, Charles P.

AU - Khan, Salmaan A.

AU - Heden, Timothy D.

AU - Witthuhn, Bruce A.

AU - Perez, Minervo

AU - Heier, Jason L.

AU - Mead, Linnea E.

AU - Franklin, Mallory P.

AU - Karanja, Kenneth K.

AU - Graham, Mark J.

AU - Mashek, Mara T.

AU - Bernlohr, David A.

AU - Parker, Laurie

AU - Chow, Lisa S.

AU - Mashek, Douglas G.

N1 - Funding Information: We would like to thank Candace Guerrero, Mitchell Fuller, Michael Autry, Colleen Forster, and Guillermo Marques for their technical assistance. We thank the University of Minnesota Imaging Center, Center for Mass Spectrometry and Proteomics, Clinical and Translational Science Biospecimen Support Center, and the Biophysical Technology Center for providing instrumentation and expertise. We thank Eduarado Chini for help with initial SIRT1 assays, Barbara Atshaves for antibodies and protocols, and Ann Hertzel for scientific discussions. Funding was provided for C.P.N. (NIH: T32DK007203 and T32AG029796), T.D.H. (NIH: F32DK109556 and L30DK110338), M.P. (NIH: R01CA182543-S1), M.P.F. (NIH: T32DK083250), D.A.B. (NIH: R01DK053189 and the University of Minnesota E-0917-2), L.S.C. (NIH: R01DK098203), and D.G.M. (NIH: R01AG055452, R01DK108790, R01DK114401, and the American Diabetes Association: 1-16-IBS-203). D.G.M. C.P.N. T.D.H. L.S.C. and S.A.K. conception and design of research; C.P.N. T.D.H. S.A.K. M.P. J.L.H. L.E.M. M.P.K. K.K.K. and M.T.M. performed experiments; C.P.N. T.D.H. S.A.K. D.G.M. and B.A.W. analyzed data; C.P.N. T.D.H. L.S.C. D.A.B. and D.G.M. interpreted results of experiments; C.P.N. S.A.K. and D.G.M. prepared figures; C.P.N. and D.G.M. drafted manuscript; M.J.G. J.L.H. and L.P. contributed materials and regents necessary for completion of studies; C.P.N. D.G.M. D.A.B. L.S.C. T.D.H. and B.A.W. edited and revised manuscript; C.P.N. S.A.K. T.D.H. B.A.W. M.P. J.L.H, L.E.M. M.P.F. K.K.K. M.J.G. M.T.M. D.A.B. L.P. L.S.C. and D.G.M. approved final version of manuscript. The authors declare no competing interests. Funding Information: We would like to thank Candace Guerrero, Mitchell Fuller, Michael Autry, Colleen Forster, and Guillermo Marques for their technical assistance. We thank the University of Minnesota Imaging Center, Center for Mass Spectrometry and Proteomics, Clinical and Translational Science Biospecimen Support Center, and the Biophysical Technology Center for providing instrumentation and expertise. We thank Eduarado Chini for help with initial SIRT1 assays, Barbara Atshaves for antibodies and protocols, and Ann Hertzel for scientific discussions. Funding was provided for C.P.N. ( NIH : T32DK007203 and T32AG029796 ), T.D.H. ( NIH : F32DK109556 and L30DK110338 ), M.P. ( NIH : R01CA182543-S1 ), M.P.F. ( NIH : T32DK083250 ), D.A.B. ( NIH : R01DK053189 and the University of Minnesota E-0917-2 ), L.S.C. ( NIH : R01DK098203 ), and D.G.M. ( NIH : R01AG055452 , R01DK108790 , R01DK114401 , and the American Diabetes Association : 1-16-IBS-203 ). Publisher Copyright: © 2019 Elsevier Inc.

PY - 2020/2/20

Y1 - 2020/2/20

N2 - Najt et al. identify the first-known endogenous allosteric modulator of SIRT1 and characterize a lipid droplet-nuclear signaling axis that underlies the known metabolic benefits of monounsaturated fatty acids and PLIN5.

AB - Najt et al. identify the first-known endogenous allosteric modulator of SIRT1 and characterize a lipid droplet-nuclear signaling axis that underlies the known metabolic benefits of monounsaturated fatty acids and PLIN5.

KW - ATGL

KW - fatty acids

KW - lipid droplets

KW - lipolysis

KW - MUFA

KW - olive oil

KW - oxidative metabolism

KW - PGC-1α

KW - PLIN5

KW - SIRT1

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JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

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Lipid Droplet-Derived Monounsaturated Fatty Acids Traffic via PLIN5 to Allosterically Activate SIRT1

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

Access

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Nikon A1RSI Confocal with SIM Super Resolution

University Imaging Centers

Cite this