Anti-inflammatory action of β-hydroxybutyrate via modulation of PGC-1α and FoxO1, mimicking calorie restriction

Aging
Dae Hyun KimHae Young Chung

Abstract

β-Hydroxybutyrate (HB) is a ketone body used as an energy source that has shown anti-inflammatory effects similar to calorie restriction (CR); Here, PGC-1α, an abundantly expressed co-factor in the kidney, was reported to interact with both FoxO1 and NF-κB although the definitive interactive mechanism has not yet been reported. In this study, we investigated whether renal aging-related inflammation is modulated by HB. We compared aged rats administered with HB to calorie restricted rats and examined the modulation of FoxO1 and the NF-κB pathway through interactions with PGC-1α. We found that in aged rats treated with HB, pro-inflammatory signaling changes were reversed and showed effects comparable to CR. As FoxO1 and its target genes catalase/MnSOD were upregulated by HB treatment and PGC-1α selectively interacted with FoxO1, not with NF-κB, and ameliorated the renal inflammatory response. These findings were further confirmed using FoxO1 overexpression and siRNA transfection in vitro. Our findings suggest that HB suppressed aging-related inflammation as a CR mimetic by enabling the co-activation and selective interaction between FoxO1 and PGC-1α. This study demonstrates the potential therapeutic role of HB as a CR mimetic, wh...Continue Reading

References

Jun 1, 1987·The Journal of Nutrition·R N HeitmannS C Sensenig
Sep 18, 2001·JAMA : the Journal of the American Medical Association·A H MokdadJ P Koplan
Sep 25, 2001·IUBMB Life·R L VeechG F Cahill
Sep 20, 2002·Nature·Geert J P L KopsBoudewijn M T Burgering
Jan 25, 2003·Science·Matthias BlüherC Ronald Kahn
May 20, 2003·Nature·Pere PuigserverBruce M Spiegelman
Feb 19, 2004·JAMA : the Journal of the American Medical Association·Caroline S FoxDaniel Levy
May 6, 2004·The Journal of Biological Chemistry·Armando van der HorstBoudewijn M T Burgering
Mar 24, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hyo-Soo KimKenneth Walsh
Apr 30, 2005·Trends in Endocrinology and Metabolism : TEM·Andreas BarthelTerry G Unterman
Aug 27, 2005·Cell·Christoph HandschinBruce M Spiegelman
Jan 15, 2008·Cellular and Molecular Life Sciences : CMLS·A SalminenK Kaarniranta
Jul 11, 2008·Cell·David J PagliariniVamsi K Mootha
Jul 31, 2008·Aging Cell·Mette Damgaard NielsenHeinrich Jasper
Sep 29, 2009·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Ian H de BoerBryan Kestenbaum
Mar 23, 2010·Cell·Kate Schroder, Jurg Tschopp
Jun 4, 2010·Antioxidants & Redox Signaling·Leanne M Redman, Eric Ravussin
Jul 9, 2010·Advances in Chronic Kidney Disease·Jessica R Weinstein, Sharon Anderson
Dec 6, 2012·Aging·Fernando G OsorioJosé M P Freije
Mar 20, 2014·Kidney & Blood Pressure Research·Kosaku NittaSusumu Takahashi
Sep 23, 2014·Archives of Pharmacal Research·Min Hi ParkHae Young Chung
Jul 15, 2015·Biochemical and Biophysical Research Communications·Petra Sabine EiseleChristoph Handschin
Dec 22, 2017·Journal of the Endocrine Society·José O AlemánAndrew J Dannenberg
May 3, 2018·GeroScience·Hak Joo LeeBalakuntalam S Kasinath

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Citations

Aug 14, 2019·European Journal of Preventive Cardiology·Katharina LechnerJohannes Scherr
Feb 6, 2020·Current Pharmaceutical Design·Jeremy J WalshJonathan P Little
May 23, 2020·Nutrients·Keisuke HagiharaTakashi Kijima
Oct 6, 2020·Oxidative Medicine and Cellular Longevity·Patrick C BradshawWilliam M Curtis
Sep 28, 2020·Current Opinion in Pharmacology·Shinsuke NirengiKristin I Stanford
Dec 30, 2020·Obesity Research & Clinical Practice·Muhammad Asyraf AbduramanMei Lan Tan
Jan 14, 2020·Redox Biology·Pedro Rojas-MoralesEdilia Tapia
May 1, 2021·Nutrients·Nicholas G NorwitzRichard S Isaacson
Jul 9, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Alexander ChoiDebra Ehrlich

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Methods Mentioned

BETA
Immunoprecipitation
ELISA
electrophoresis
Assay

Software Mentioned

ATTO Densitograph
GraphPad Prism

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