A ketogenic diet can mitigate SARS-CoV-2 induced systemic reprogramming and inflammation

Amelia Palermo; Shen Li; Johanna Ten Hoeve; Akshay Chellappa; Alexandra Morris; Barbara Dillon; Feiyang Ma; Yijie Wang; Edward Cao; Byourak Shabane; Rebeca Acín-Perez; Anton Petcherski; A Jake Lusis; Stanley Hazen; Orian S Shirihai; Matteo Pellegrini; Vaithilingaraja Arumugaswami; Thomas G Graeber; Arjun Deb

doi:10.1038/s42003-023-05478-7

A ketogenic diet can mitigate SARS-CoV-2 induced systemic reprogramming and inflammation

Commun Biol. 2023 Nov 3;6(1):1115. doi: 10.1038/s42003-023-05478-7.

Authors

Amelia Palermo^#^{1

2

3

4}, Shen Li^#^{5

6

7

8

9

10}, Johanna Ten Hoeve^{2

3

4}, Akshay Chellappa¹, Alexandra Morris¹, Barbara Dillon¹¹, Feiyang Ma¹², Yijie Wang^{6

7

8

9

10}, Edward Cao^{6

7

8

9

10}, Byourak Shabane¹³, Rebeca Acín-Perez¹³, Anton Petcherski¹³, A Jake Lusis^{2

6}, Stanley Hazen¹⁴, Orian S Shirihai^{2

13}, Matteo Pellegrini^{7

8

9}, Vaithilingaraja Arumugaswami^{1

8}, Thomas G Graeber^{15

16

17

18

19}, Arjun Deb^{20

21

22

23

24

25}

Affiliations

¹ Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
² California Nanosystems Institute, University of California, Los Angeles, CA, 90095, USA.
³ UCLA Metabolomics Center, University of California, Los Angeles, CA, 90095, USA.
⁴ Crump Institute for Molecular Imaging, University of California, Los Angeles, CA, 90095, USA.
⁵ Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
⁶ UCLA Cardiovascular Research Theme, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
⁷ Department of Molecular, Cell and Developmental Biology, Division of Life Sciences, University of California, Los Angeles, CA, 90095, USA.
⁸ Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, 90095, USA.
⁹ Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA.
¹⁰ Department of Genetics, David Geffen School of Medicine, Los Angeles, CA, 90095, USA.
¹¹ Department of Environment, Health and Safety, University of California, Los Angeles, CA, 90095, USA.
¹² Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, 48109, USA.
¹³ Department of Medicine, Endocrinology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
¹⁴ Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH, 44195, USA.
¹⁵ Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA. tgraeber@mednet.ucla.edu.
¹⁶ California Nanosystems Institute, University of California, Los Angeles, CA, 90095, USA. tgraeber@mednet.ucla.edu.
¹⁷ UCLA Metabolomics Center, University of California, Los Angeles, CA, 90095, USA. tgraeber@mednet.ucla.edu.
¹⁸ Crump Institute for Molecular Imaging, University of California, Los Angeles, CA, 90095, USA. tgraeber@mednet.ucla.edu.
¹⁹ Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, 90095, USA. tgraeber@mednet.ucla.edu.
²⁰ California Nanosystems Institute, University of California, Los Angeles, CA, 90095, USA. adeb@mednet.ucla.edu.
²¹ Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA. adeb@mednet.ucla.edu.
²² UCLA Cardiovascular Research Theme, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA. adeb@mednet.ucla.edu.
²³ Department of Molecular, Cell and Developmental Biology, Division of Life Sciences, University of California, Los Angeles, CA, 90095, USA. adeb@mednet.ucla.edu.
²⁴ Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, 90095, USA. adeb@mednet.ucla.edu.
²⁵ Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA. adeb@mednet.ucla.edu.

^# Contributed equally.

Abstract

The ketogenic diet (KD) has demonstrated benefits in numerous clinical studies and animal models of disease in modulating the immune response and promoting a systemic anti-inflammatory state. Here we investigate the effects of a KD on systemic toxicity in mice following SARS-CoV-2 infection. Our data indicate that under KD, SARS-CoV-2 reduces weight loss with overall improved animal survival. Muted multi-organ transcriptional reprogramming and metabolism rewiring suggest that a KD initiates and mitigates systemic changes induced by the virus. We observed reduced metalloproteases and increased inflammatory homeostatic protein transcription in the heart, with decreased serum pro-inflammatory cytokines (i.e., TNF-α, IL-15, IL-22, G-CSF, M-CSF, MCP-1), metabolic markers of inflammation (i.e., kynurenine/tryptophane ratio), and inflammatory prostaglandins, indicative of reduced systemic inflammation in animals infected under a KD. Taken together, these data suggest that a KD can alter the transcriptional and metabolic response in animals following SARS-CoV-2 infection with improved mice health, reduced inflammation, and restored amino acid, nucleotide, lipid, and energy currency metabolism.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
COVID-19*
Cytokines
Diet, Ketogenic*
Inflammation
Mice
SARS-CoV-2

Substances

Cytokines

Abstract

Publication types

MeSH terms

Substances

Grants and funding