Proanthocyanidin trimer gallate modulates lipid deposition and fatty acid desaturation in Caenorhabditis elegans

The incidence of obesity is rising at an alarming rate. Despite its recognition as an urgent healthcare concern, obesity remains largely an unsolved medical problem. A comprehensive screen for functional dietary phytochemicals identified proanthocyanidins as putative targets to ameliorate obesity. A...

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Bibliographic Details
Published in:The FASEB journal 2017-11, Vol.31 (11), p.4891-4902
Main Authors: Nie, Yu, Littleton, Brad, Kavanagh, Thomas, Abbate, Vincenzo, Bansal, Sukhvinder S., Richards, David, Hylands, Peter, Stürzenbaum, Stephen R.
Format: Article
Language:English
Subjects:
Animals
Biological activity
Caenorhabditis elegans
Caenorhabditis elegans - genetics
Caenorhabditis elegans - metabolism
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - metabolism
CARS
Coherent scattering
Deposition
Desaturation
Diet
Down-regulation
Exposure
Fat metabolism
Fatty acids
Fatty Acids - genetics
Fatty Acids - metabolism
foam cell
Gallates
Gene regulation
Health care
Lipase
Lipid Metabolism - drug effects
Lipid Metabolism - physiology
Lipids
Metabolism
Microscopy
natural product
Nematodes
Obesity
Plant extracts
Proanthocyanidins
Proanthocyanidins - pharmacology
procyanidin
Purification
Raman spectra
Receptors, Cytoplasmic and Nuclear - genetics
Receptors, Cytoplasmic and Nuclear - metabolism
Seeds
Storage capacity
Target recognition
Traditional Chinese medicine
Transcription
triglyceride
worm
Worms
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Summary:The incidence of obesity is rising at an alarming rate. Despite its recognition as an urgent healthcare concern, obesity remains largely an unsolved medical problem. A comprehensive screen for functional dietary phytochemicals identified proanthocyanidins as putative targets to ameliorate obesity. A full‐scale purification of oligomeric proanthocyanidins (OPCs) derived from grape seed extract yielded pure OPC dimer, trimer, tetramer, and their gallates (pOPCs). Forward chemical screening conducted in Caenorhabditis elegans suggested that pOPCs reduced the activity of lipase in vitro and triglyceride storage capacity in vivo. Proanthocyanidin trimer gallate in particular modified lipid desaturation in C. elegans, revealed by hyperspectral coherent anti‐Stokes Raman scattering microscopy. Exposure to trimer gallate resulted in the transcriptional down‐regulation of nhr‐49 (an ortholog of the human peroxisome proliferator‐activated receptor‐a), and a key regulator of fat metabolism, and 2 downstream genes: fat‐5 and acs‐2. A combination exposure of 2 or 3 pOPCs (dimer gallate, trimer and/or trimer gallate) suggested the absence of synergistic potential. By using the whole‐organism C. elegans coupled with versatile biochemical, biophysical, and genetic tools, we provide an account of the composition and bioactivity of individual OPCs and more generally highlight the potential of traditional Chinese medicine–derived drug leads.—Nie, Y., Littleton, B., Kavanagh, T., Abbate, V., Bansal, S. S., Richards, D., Hylands, P., Stürzenbaum, S. R. Proanthocyanidin trimer gallate modulates lipid deposition and fatty acid desaturation in Caenorhabditis elegans. FASEB J. 31, 4891–4902 (2017). www.fasebj.org
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.201700438R