NMN may become the next dark horse in the fight against obesity and age-related metabolic decline.
Global population aging is becoming increasingly pronounced. It is estimated that by 2050, the number of people aged 65 and above will reach 1.6 billion—double the 780 million recorded in 2020. As aging progresses, fat in the human body tends to redistribute, leading to ectopic accumulation in organs such as the liver, muscles, and bones.
In modern life, common sedentary habits and high-fat diets further aggravate age-related metabolic disorders. NAD⁺ (nicotinamide adenine dinucleotide), a key molecule in cellular energy metabolism, plays an essential role in glycolysis, the tricarboxylic acid (TCA) cycle, and mitochondrial respiration. However, NAD⁺ levels decline with age. Therefore, promoting NAD⁺ biosynthesis is considered a promising strategy to alleviate the physiological decline associated with aging.
In January 2025, a study published in The Journal of Nutrition reported that NMN supplementation increased NAD⁺ levels in mice, thereby suppressing high-fat diet (HFD)-induced obesity, improving glucose and lipid metabolism, enhancing skeletal muscle function, and alleviating kidney damage. In addition, NMN reduced the levels of aging- and inflammation-related markers such as p16, interleukin-1β, and tumor necrosis factor-α (TNF-α), ultimately mitigating physiological decline associated with aging and diet.
Long-term supplementation with nicotinamide mononucleotide (NMN) can alleviate physiological decline in aging mice induced by a high-fat diet.
NMN can reduce obesity and delay aging
Researchers added NMN (400 mg/kg body weight) to the drinking water of middle-aged mice fed a high-fat diet (HFD) for seven months to observe its effects on various organs. The results showed that long-term NMN supplementation reduced body weight in HFD-fed mice after four months of intervention. Magnetic resonance imaging (MRI) analysis of body composition revealed that NMN treatment significantly decreased total body fat and liver fat content in the mice, indicating that NMN helped slow down the aging process induced by a high-fat diet.
Long-term NMN administration reduces obesity and delays aging in HFD-treated mice
NMN enhances energy metabolism and physical activity
Studies have shown that after seven months of a high-fat diet (HFD), NMN supplementation significantly improved the resulting energy metabolism disorders and reduced physical activity in mice. Mechanistically, NMN intervention not only increased oxygen consumption—thereby enhancing overall energy expenditure—but also elevated the respiratory exchange ratio (RER), indicating a metabolic shift from primarily fatty acid oxidation to greater glucose utilization. Behavioral observations further confirmed that, compared with mice fed only an HFD, those treated with NMN exhibited significantly higher physical activity during the dark phase. Together, these results demonstrate that NMN administration can effectively reverse HFD-induced energy metabolism dysfunction and reduced spontaneous activity.
Long-term NMN administration enhances energy metabolism and physical activity during dark hours in HFD-treated mice
NMN can improve blood sugar and blood lipid status
An oral glucose tolerance test (OGTT) revealed that long-term NMN treatment significantly improved glucose tolerance in mice fed a high-fat diet (HFD). Regarding blood lipid levels, the results showed that NMN administration markedly reduced HFD-induced elevations in triglycerides (TG) and low-density lipoprotein (LDL) cholesterol, while also slightly improving total cholesterol (TC) levels.
Long-term NMN administration improves blood glucose and lipid profiles in HFD-treated mice
NMN improves pathological changes in peripheral tissues of HFD-treated mice
To further evaluate the effects of long-term NMN intervention on organ tissues, researchers conducted histopathological analyses. In adipose tissue, compared with mice fed a normal diet (ND), high-fat diet (HFD) mice exhibited significantly enlarged adipocytes, abnormal morphology, and increased intracellular lipid vacuoles. NMN treatment markedly reduced adipocyte cross-sectional area and improved adipocyte arrangement and morphology. In kidney tissue, NMN intervention not only alleviated HFD-induced glomerular atrophy and tubulointerstitial inflammatory cell infiltration but also significantly reduced the degree of tissue fibrosis.
Long-term administration of NMN improves pathological changes in peripheral tissues of HFD-treated mice
NMN can improve skeletal muscle dysfunction
Researchers used wire-hang and rotarod tests to evaluate the effects of NMN intervention on skeletal muscle function. The results showed that, compared with mice fed a normal diet (ND), high-fat diet (HFD) mice exhibited significantly shorter retention times in both tests, indicating reduced muscle strength and coordination. However, long-term NMN treatment markedly increased the retention times of HFD-fed mice. Correspondingly, H&E-stained morphological analysis of the gastrocnemius muscle revealed that NMN treatment increased muscle fiber cross-sectional area and resulted in more compact alignment. Together, these behavioral and morphological findings demonstrate that NMN effectively improves skeletal muscle function in HFD-fed mice.
Long-term NMN administration improves skeletal muscle dysfunction in HFD-treated mice
Effects of NMN on SIRT1/SIRT3 activities in peripheral organs of HFD mice
After confirming that NMN could reverse the decline in blood NAD⁺ levels induced by a high-fat diet (HFD) in mice, researchers further investigated whether NMN could activate NAD⁺-dependent deacetylases such as SIRT1 and SIRT3. Western blot (WB) analysis showed that long-term NMN treatment not only increased SIRT1 expression in the adipose and skeletal muscle tissues of HFD-fed mice but also elevated SIRT3 protein levels in skeletal muscle.
Effects of long-term NMN administration on SIRT1/SIRT3 activity in peripheral organs of HFD-treated mice
Summary
This study confirmed that NMN, as a bioactive molecule, can effectively alleviate multi-organ physiological decline in mice fed a high-fat diet, including improving metabolism, reducing histopathological damage, and enhancing muscle function. These findings open up new avenues for developing NMN-based anti-aging strategies.
In modern life, common sedentary habits and high-fat diets further aggravate age-related metabolic disorders. NAD⁺ (nicotinamide adenine dinucleotide), a key molecule in cellular energy metabolism, plays an essential role in glycolysis, the tricarboxylic acid (TCA) cycle, and mitochondrial respiration. However, NAD⁺ levels decline with age. Therefore, promoting NAD⁺ biosynthesis is considered a promising strategy to alleviate the physiological decline associated with aging.
In January 2025, a study published in The Journal of Nutrition reported that NMN supplementation increased NAD⁺ levels in mice, thereby suppressing high-fat diet (HFD)-induced obesity, improving glucose and lipid metabolism, enhancing skeletal muscle function, and alleviating kidney damage. In addition, NMN reduced the levels of aging- and inflammation-related markers such as p16, interleukin-1β, and tumor necrosis factor-α (TNF-α), ultimately mitigating physiological decline associated with aging and diet.
Long-term supplementation with nicotinamide mononucleotide (NMN) can alleviate physiological decline in aging mice induced by a high-fat diet.
NMN can reduce obesity and delay aging
Researchers added NMN (400 mg/kg body weight) to the drinking water of middle-aged mice fed a high-fat diet (HFD) for seven months to observe its effects on various organs. The results showed that long-term NMN supplementation reduced body weight in HFD-fed mice after four months of intervention. Magnetic resonance imaging (MRI) analysis of body composition revealed that NMN treatment significantly decreased total body fat and liver fat content in the mice, indicating that NMN helped slow down the aging process induced by a high-fat diet.
Long-term NMN administration reduces obesity and delays aging in HFD-treated mice
NMN enhances energy metabolism and physical activity
Studies have shown that after seven months of a high-fat diet (HFD), NMN supplementation significantly improved the resulting energy metabolism disorders and reduced physical activity in mice. Mechanistically, NMN intervention not only increased oxygen consumption—thereby enhancing overall energy expenditure—but also elevated the respiratory exchange ratio (RER), indicating a metabolic shift from primarily fatty acid oxidation to greater glucose utilization. Behavioral observations further confirmed that, compared with mice fed only an HFD, those treated with NMN exhibited significantly higher physical activity during the dark phase. Together, these results demonstrate that NMN administration can effectively reverse HFD-induced energy metabolism dysfunction and reduced spontaneous activity.
Long-term NMN administration enhances energy metabolism and physical activity during dark hours in HFD-treated mice
NMN can improve blood sugar and blood lipid status
An oral glucose tolerance test (OGTT) revealed that long-term NMN treatment significantly improved glucose tolerance in mice fed a high-fat diet (HFD). Regarding blood lipid levels, the results showed that NMN administration markedly reduced HFD-induced elevations in triglycerides (TG) and low-density lipoprotein (LDL) cholesterol, while also slightly improving total cholesterol (TC) levels.
Long-term NMN administration improves blood glucose and lipid profiles in HFD-treated mice
NMN improves pathological changes in peripheral tissues of HFD-treated mice
To further evaluate the effects of long-term NMN intervention on organ tissues, researchers conducted histopathological analyses. In adipose tissue, compared with mice fed a normal diet (ND), high-fat diet (HFD) mice exhibited significantly enlarged adipocytes, abnormal morphology, and increased intracellular lipid vacuoles. NMN treatment markedly reduced adipocyte cross-sectional area and improved adipocyte arrangement and morphology. In kidney tissue, NMN intervention not only alleviated HFD-induced glomerular atrophy and tubulointerstitial inflammatory cell infiltration but also significantly reduced the degree of tissue fibrosis.
Long-term administration of NMN improves pathological changes in peripheral tissues of HFD-treated mice
NMN can improve skeletal muscle dysfunction
Researchers used wire-hang and rotarod tests to evaluate the effects of NMN intervention on skeletal muscle function. The results showed that, compared with mice fed a normal diet (ND), high-fat diet (HFD) mice exhibited significantly shorter retention times in both tests, indicating reduced muscle strength and coordination. However, long-term NMN treatment markedly increased the retention times of HFD-fed mice. Correspondingly, H&E-stained morphological analysis of the gastrocnemius muscle revealed that NMN treatment increased muscle fiber cross-sectional area and resulted in more compact alignment. Together, these behavioral and morphological findings demonstrate that NMN effectively improves skeletal muscle function in HFD-fed mice.
Long-term NMN administration improves skeletal muscle dysfunction in HFD-treated mice
Effects of NMN on SIRT1/SIRT3 activities in peripheral organs of HFD mice
After confirming that NMN could reverse the decline in blood NAD⁺ levels induced by a high-fat diet (HFD) in mice, researchers further investigated whether NMN could activate NAD⁺-dependent deacetylases such as SIRT1 and SIRT3. Western blot (WB) analysis showed that long-term NMN treatment not only increased SIRT1 expression in the adipose and skeletal muscle tissues of HFD-fed mice but also elevated SIRT3 protein levels in skeletal muscle.
Effects of long-term NMN administration on SIRT1/SIRT3 activity in peripheral organs of HFD-treated mice
Summary
This study confirmed that NMN, as a bioactive molecule, can effectively alleviate multi-organ physiological decline in mice fed a high-fat diet, including improving metabolism, reducing histopathological damage, and enhancing muscle function. These findings open up new avenues for developing NMN-based anti-aging strategies.
