The effect of obesity and aging on NAD+/Sirtuin metabolism transcription and DNA methylation in subcutaneous adipose tissue of monozygotic twin pairs discordant for BMI
Impaired NAD<sup>+</sup>/SIRT metabolism in AT may play a key role in obesity- and aging-related diseases. Both conditions are characterized by downregulation of NAD<sup>+</sup>/SIRT pathway genes, correlating with increased adiposity, insulin resistance, inflammation, and dyslipidemia. Obesity uniquely disrupts expression of NAD<sup>+</sup>/SIRT regulated mitochondrial genes, while aging is characterized by altered PARP expression, particularly increased PARP1, likely exacerbating metabolic dysfunction in AT.
Authors
- Riikka Jokinen
- Taru Tukiainen (ORCID: https://orcid.org/0000-0002-5404-8398)
- Birgitta W. van der Kolk (ORCID: https://orcid.org/0000-0001-8608-541X)
- Eija Pirinen (ORCID: https://orcid.org/0000-0003-1495-3972)
- Aino Heikkinen (ORCID: https://orcid.org/0000-0001-5770-6475)
- Juho Kuula (ORCID: https://orcid.org/0000-0002-5793-9196)
- Seung Hyuk Lee (ORCID: https://orcid.org/0000-0002-0943-6076)
- Helena A. K. Lapatto (ORCID: https://orcid.org/0000-0002-6655-4415)
- Marcus Alvarez (ORCID: https://orcid.org/0000-0002-6369-5028)
- Maheswary Muniandy (ORCID: https://orcid.org/0000-0001-7624-7948)
- Päivi Pajukanta
- Jesper Lundbom
- Kirsi H. Pietiläinen
- Per-Henrik Groop
- Sini Heinonen
- Antti Hakkarainen
- Jaakko Kaprio
- Miina Ollikainen
Institutions
- University of Helsinki (FI)
- University of California, Los Angeles (US)
- Oulu University Hospital (FI)
- Helsinki University Hospital (FI)
- Finnish Institute for Health and Welfare (FI)
- Minerva Foundation (FI)
- Institute for Molecular Medicine Finland (FI)
- Folkhälsans Forskningscentrum (FI)
- Monash University (AU)
- University of Oulu (FI)
Publication Details
- Journal
- International Journal of Obesity
- Published
- 2026-01-05
- DOI
- https://doi.org/10.1038/s41366-025-02007-w
- Primary Topic
- Sirtuins and Resveratrol in Medicine
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Howard Hughes Medical Institute
- Foundation for Cardiovascular Research
- Helsingin Yliopisto
- Suomen Lääketieteen Säätiö
- Finska Läkaresällskapet
- European Foundation for the Study of Diabetes
- Novo Nordisk
- Sydäntutkimussäätiö
- Sigrid Juséliuksen Säätiö
- Orionin Tutkimussäätiö
- Paavo Nurmen Säätiö
- Novo Nordisk Fonden
- Diabetestutkimussäätiö