A Key Role for NMN in Alleviating Organelle Miscommunication in HFD Mouse Liver

A Key Role for NMN in Alleviating Organelle Miscommunication in HFD Mouse Liver


Recent research unveils that hepatic insulin resistance (IR) and steatosis in obesity have a strong association with endoplasmic reticulum (ER)-mitochondria miscommunication. Notably, β-nicotinamide mononucleotide (NMN) can ameliorate hepatic IR and steatosis to regulate obesity via reinforcing the interaction between ER and mitochondria.


About ER-mitochondria miscommunication

ER and mitochondria interact at contact sites called mitochondria-associated membranes (MAMs), where they exchange phospholipids and calcium (Ca2+). MAM acts as a bridge between the ER and mitochondria, participating in the regulation of calcium signaling, lipid homeostasis, mitochondrial dynamics, mitochondrial autophagy, and ER stress response. Disrupting ER-mitochondria communication may induce hepatic IR and steatosis.


Research protocol

In vivo, thirty 8-week-old male C57BL/6 J specific pathogen-free mice are fed with normal/high-fat diet (HFD) and normal/NMN-containing drinking water for 30 weeks.  During the experiments, the body weight, diet, food intake, appearance, and behavior characteristics of the experimental mice are recorded weekly. A week prior to the end of study, 12-h-fasting mice are subjected with intraperitoneal injection of glucose (2 mg/g body weight) or insulin (0.75 mU/g body weight) for glucose tolerance test and insulin tolerance test, followed by the measurement of glycemia using a glucometer.

In vitro, mouse normal hepatocytes NCTC1469 are seeded in 96-well microtiter plates for 12-h culture, then blended with specific palmitic acid (PA) for 36 h to establish the HFD model, and treated with NMN (500, 50, 5, 0.5, and 0.05 μM) for 24 h, followed by detection of physiological indicators.

Regulatory impacts of NMN upon obesity

In vivo, NMN ameliorates hyperlipidemia, hepatic steatosis, liver physiological metabolic damage, liver lipid metabolic abnormalities, and ER-mitochondrial miscommunication in the liver of HFD mice.
In vitro, NMN reduces PA-induced lipid accumulation, yet promotes PA-induced mitochondrial-ER communication in NCTC1469 cells.



NMN alleviates organelle miscommunication by increasing MAMs in HFD mice liver. Concretely, NMN ameliorates mitochondrial dysfunction and ER oxidative stress in the liver of HFD mice by increasing hepatic nicotinamide adenine dinucleotide (NAD+) level. This effect increases the MAMs between ER and mitochondria, thereby promoting intracellular ATP production and mitigating lipid metabolic disturbances in the liver of HFD mice.


NMN enhances the dynamic properties of MAMs to increase the communication between mitochondria and ER, ultimately reversing HFD-induced glycolipid metabolic disorder, IR and hepatic steatosis. 


[1] Beaulant A, Dia M, Pillot B, et al. Endoplasmic reticulum-mitochondria miscommunication is an early and causal trigger of hepatic insulin resistance and steatosis. J Hepatol. 2022;77(3):710-722. DOI:10.1016/j.jhep.2022.03.017
[2] Lam BCC, Lim AYL, Chan SL, et al. The impact of obesity: a narrative review. Singapore Med J. 2023;64(3):163-171. DOI: 10.4103/singaporemedj.SMJ-2022-232
[3] Li Y, Tian X, Yu Q, et al. Alleviation of hepatic insulin resistance and steatosis with NMN via improving endoplasmic reticulum-mitochondria miscommunication in the liver of HFD mice. Biomed Pharmacother. Published online May 3, 2024. DOI:10.1016/j.biopha.2024.116682


BONTAC is the pioneer of NMN industry and the first manufacturer to launch NMN mass production, with the first whole-enzyme catalysis technology around the world. BONTAC NMN is patent-grade and has obtained the self-affirmed GRAS certification of FDA. At present, BONTAC has become the leading enterprise in niche areas of coenzyme. Our services and products have been highly recognized by global partners. Furthermore, BONTAC has the first national and the only provincial independent coenzyme engineering technology research center in Guangdong, China. The coenzyme products of BONTAC are widely used in fields such as nutritional health, biomedicine, medical beauty, daily chemicals and green agriculture.


This article is based on the reference in the academic journal. The relevant information is provided for sharing and learning purposes only, and does not represent any medical advice purposes. If there is any infringement, please contact the author for deletion. The views expressed in this article do not represent the position of BONTAC. Under no circumstances will BONTAC be responsible for any claims, damages, losses, expenses or costs resulting directly or indirectly from your reliance on the information and material on this website.

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