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Topical Area: Dietary Bioactive Components

Dietary Bioactive Components (Poster Session)

(P03-046-23) Transcriptomic Analysis Revealed Tissue-Specific Effects of Short-Term Nicotinamide Mononucleotide Treatment in Liver and Adipose Tissue

Saturday, July 22, 2023

12:00 PM – 1:00 PM ET

Location: Poster Board 461

Presenting Author(s)

SK

So Young Kwon, Master's degree (she/her/hers)

Student
Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Republic of Korea, Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, Republic of Korea
Seoul, Seoul-t'ukpyolsi, Republic of Korea

Co-Author(s)

KN

Khu Hee Na

Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Republic of Korea, Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, Republic of Korea
SS

Seung Min Song

Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Republic of Korea, Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, Republic of Korea
YP

Yoon Jung Park, Ph.D.

Department of Nutritional Science and Food Management, Ewha Womans University, Republic of Korea, Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, Korea
Seodaemun-gu, Seoul-t'ukpyolsi, Republic of Korea

Disclosure(s):

So Young Kwon, Master's degree: No relevant financial relationship(s) with ineligible companies to disclose.

Objectives: Supplementation of nicotinamide adenine dinucleotide (NAD) precursors, such as nicotinamide mononucleotide (NMN), is known as anti-aging and anti-obesity properties, mainly through a long-term intervention. This study investigated tissue-specific metabolic effects of short-term NMN treatment in the liver and WAT using multiple transcriptomic analysis.

Methods: 10-week-old male wild type mice, fed control diet (CD) or high fat diet (HFD) for 6 weeks, were administrated every other day with NMN (500mg/kg) for 4 weeks. Body weight, food and water intake were measured every week and glucose tolerance test was conducted at the end of the intervention. Liver and inguinal WAT were collected for further analysis. RNA-sequencing data analysis was conducted to analyze differentially expressed genes (DEGs), followed by RT-PCR validation. Public data on NMN supplements (GSE31647 and GSE86718 for a short-term with HFD and a long-term on CD, respectively) were analyzed for comparison with our DEGs and EnrichR analysis.

Results: NMN supplement significantly reduced body weight and fat mass in both CD and HFD groups and marginally improved glucose tolerance in HFD group. In the liver, it alleviated HFD-induced endoplasmic reticulum (ER) stress. EnrichR analysis indicated the motif for a core circadian clock component ARNTL was enriched, suggesting the alleviation from ER stress might be mediated by boosting circadian rhythm. The effect likely sustained for a long term as well, since the same motif was enriched in the hepatic transcriptome after 12-month treatment. On the other hand, NMN supplement had slightly different molecular phenotypes in WAT between CD and HFD groups. NMN in CD group elevated de novo lipogenesis, while that in HFD group reduced lipid biosynthesis pathway and upregulated genes related with muscle development and thermogenesis, including Sirt1.

Conclusions: NMN supplement attenuated hepatic HFD-induced ER stress likely via boosting circadian oscillation, while regulated adipocytic lipid biosynthesis and thermogenesis depending on metabolic status (CD vs HFD).

Funding Sources: This study was supported by Basic Research Programs and the BK21 FOUR (Fostering Outstanding Universities for Research) through the National Research Foundation (NRF) funded by the Ministry of Education.