Dietary Nicotinamide Mononucleotide, a Key NAD<sup>+</sup> Intermediate, Alleviates Body Fat Mass and Hypertriglyceridemia by Enhancing Energy Expenditure with Promotion of Fat Oxidation and Hepatic Lipolysis and Suppressing Hepatic Lipogenesis in <i>db/db</i> Mice
<b>Background/Objectives</b>: Supplementation with nicotinamide mononucleotide (NMN), a key nicotinamide adenine dinucleotide (NAD<sup>+</sup>) intermediate, exerts anti-aging, anti-obesity, and anti-diabetic effects in animal experiments. However, previous studies have evalu...
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| author | Bungo Shirouchi Sarasa Mitsuta Mina Higuchi Mai Okumura Kazunari Tanaka |
| author_facet | Bungo Shirouchi Sarasa Mitsuta Mina Higuchi Mai Okumura Kazunari Tanaka |
| author_sort | Bungo Shirouchi |
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| description | <b>Background/Objectives</b>: Supplementation with nicotinamide mononucleotide (NMN), a key nicotinamide adenine dinucleotide (NAD<sup>+</sup>) intermediate, exerts anti-aging, anti-obesity, and anti-diabetic effects in animal experiments. However, previous studies have evaluated NMN supplementation using oral administration in drinking water or by intraperitoneal administration. No studies have reported whether NMN exerts beneficial effects when incorporated into the diet. The diet is a multicomponent mixture of many nutrients that may interact with each other, thus weakening the effects of NMN. In the present study, we evaluated whether dietary NMN intake protects obese diabetic <i>db/db</i> mice from obesity-related metabolic disorders, such as dyslipidemia, hepatic steatosis, hyperglycemia, and hyperinsulinemia. <b>Methods</b>: Five-week-old male <i>db/db</i> mice were randomly assigned to two groups and fed for four weeks either a control diet containing 7% corn oil and 0.1% cholesterol (CON group, <i>n</i> = 6) or a diet supplemented with 0.5% NMN (NMN group, <i>n</i> = 5). <b>Results</b>: After 4 weeks of feeding, dietary NMN intake alleviated obesity, hypertriglyceridemia, and hepatic triglyceride accumulation in <i>db/db</i> mice. Respiratory gas analysis indicated that dietary NMN intake significantly enhanced energy expenditure by suppressing carbohydrate oxidation and increasing fat oxidation after 3 weeks of feeding. Additionally, the suppression of the increase in plasma triglyceride (TG) levels by dietary NMN intake was attributable to a reduction in hepatic TG levels through the suppression of fatty acid synthesis and the enhancement of fatty acid β-oxidation in the liver. Furthermore, the improvement in hepatic fatty acid metabolism induced by dietary NMN intake was partially responsible for the significant increase in plasma adiponectin and soluble T-cadherin levels. <b>Conclusions</b>: This is the first report to show that dietary NMN intake but not oral administration in drinking water or intraperitoneal administration alleviates body fat mass and hypertriglyceridemia by enhancing energy expenditure, with preferential promotion of fat oxidation, the enhancement of hepatic lipolysis, and the suppression of hepatic lipogenesis in <i>db/db</i> mice. |
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| institution | DOAJ |
| issn | 2218-1989 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-35340572df5a4d4cbfeae807c321d3ec2025-08-20T03:14:39ZengMDPI AGMetabolites2218-19892025-05-0115533310.3390/metabo15050333Dietary Nicotinamide Mononucleotide, a Key NAD<sup>+</sup> Intermediate, Alleviates Body Fat Mass and Hypertriglyceridemia by Enhancing Energy Expenditure with Promotion of Fat Oxidation and Hepatic Lipolysis and Suppressing Hepatic Lipogenesis in <i>db/db</i> MiceBungo Shirouchi0Sarasa Mitsuta1Mina Higuchi2Mai Okumura3Kazunari Tanaka4Department of Nutrition Science, Faculty of Nursing and Nutrition, University of Nagasaki, Siebold, 1-1-1 Manabino, Nagayo-cho, Nishi-Sonogi-gun, Nagasaki 851-2195, JapanNutrition Science Course, Division of Human Health Science, Graduate School of Regional Design and Creation, University of Nagasaki, Siebold, 1-1-1 Manabino, Nagayo-cho, Nishi-Sonogi-gun, Nagasaki 851-2195, JapanNutrition Science Course, Division of Human Health Science, Graduate School of Regional Design and Creation, University of Nagasaki, Siebold, 1-1-1 Manabino, Nagayo-cho, Nishi-Sonogi-gun, Nagasaki 851-2195, JapanNutrition Science Course, Division of Human Health Science, Graduate School of Regional Design and Creation, University of Nagasaki, Siebold, 1-1-1 Manabino, Nagayo-cho, Nishi-Sonogi-gun, Nagasaki 851-2195, JapanRegional Partnership Center, University of Nagasaki, Siebold, 1-1-1 Manabino, Nagayo-cho, Nishi-Sonogi-gun, Nagasaki 851-2195, Japan<b>Background/Objectives</b>: Supplementation with nicotinamide mononucleotide (NMN), a key nicotinamide adenine dinucleotide (NAD<sup>+</sup>) intermediate, exerts anti-aging, anti-obesity, and anti-diabetic effects in animal experiments. However, previous studies have evaluated NMN supplementation using oral administration in drinking water or by intraperitoneal administration. No studies have reported whether NMN exerts beneficial effects when incorporated into the diet. The diet is a multicomponent mixture of many nutrients that may interact with each other, thus weakening the effects of NMN. In the present study, we evaluated whether dietary NMN intake protects obese diabetic <i>db/db</i> mice from obesity-related metabolic disorders, such as dyslipidemia, hepatic steatosis, hyperglycemia, and hyperinsulinemia. <b>Methods</b>: Five-week-old male <i>db/db</i> mice were randomly assigned to two groups and fed for four weeks either a control diet containing 7% corn oil and 0.1% cholesterol (CON group, <i>n</i> = 6) or a diet supplemented with 0.5% NMN (NMN group, <i>n</i> = 5). <b>Results</b>: After 4 weeks of feeding, dietary NMN intake alleviated obesity, hypertriglyceridemia, and hepatic triglyceride accumulation in <i>db/db</i> mice. Respiratory gas analysis indicated that dietary NMN intake significantly enhanced energy expenditure by suppressing carbohydrate oxidation and increasing fat oxidation after 3 weeks of feeding. Additionally, the suppression of the increase in plasma triglyceride (TG) levels by dietary NMN intake was attributable to a reduction in hepatic TG levels through the suppression of fatty acid synthesis and the enhancement of fatty acid β-oxidation in the liver. Furthermore, the improvement in hepatic fatty acid metabolism induced by dietary NMN intake was partially responsible for the significant increase in plasma adiponectin and soluble T-cadherin levels. <b>Conclusions</b>: This is the first report to show that dietary NMN intake but not oral administration in drinking water or intraperitoneal administration alleviates body fat mass and hypertriglyceridemia by enhancing energy expenditure, with preferential promotion of fat oxidation, the enhancement of hepatic lipolysis, and the suppression of hepatic lipogenesis in <i>db/db</i> mice.https://www.mdpi.com/2218-1989/15/5/333NMNobesitydyslipidemiarespiratory gas analysismetabolic profilehepatic fatty acid metabolism |
| spellingShingle | Bungo Shirouchi Sarasa Mitsuta Mina Higuchi Mai Okumura Kazunari Tanaka Dietary Nicotinamide Mononucleotide, a Key NAD<sup>+</sup> Intermediate, Alleviates Body Fat Mass and Hypertriglyceridemia by Enhancing Energy Expenditure with Promotion of Fat Oxidation and Hepatic Lipolysis and Suppressing Hepatic Lipogenesis in <i>db/db</i> Mice Metabolites NMN obesity dyslipidemia respiratory gas analysis metabolic profile hepatic fatty acid metabolism |
| title | Dietary Nicotinamide Mononucleotide, a Key NAD<sup>+</sup> Intermediate, Alleviates Body Fat Mass and Hypertriglyceridemia by Enhancing Energy Expenditure with Promotion of Fat Oxidation and Hepatic Lipolysis and Suppressing Hepatic Lipogenesis in <i>db/db</i> Mice |
| title_full | Dietary Nicotinamide Mononucleotide, a Key NAD<sup>+</sup> Intermediate, Alleviates Body Fat Mass and Hypertriglyceridemia by Enhancing Energy Expenditure with Promotion of Fat Oxidation and Hepatic Lipolysis and Suppressing Hepatic Lipogenesis in <i>db/db</i> Mice |
| title_fullStr | Dietary Nicotinamide Mononucleotide, a Key NAD<sup>+</sup> Intermediate, Alleviates Body Fat Mass and Hypertriglyceridemia by Enhancing Energy Expenditure with Promotion of Fat Oxidation and Hepatic Lipolysis and Suppressing Hepatic Lipogenesis in <i>db/db</i> Mice |
| title_full_unstemmed | Dietary Nicotinamide Mononucleotide, a Key NAD<sup>+</sup> Intermediate, Alleviates Body Fat Mass and Hypertriglyceridemia by Enhancing Energy Expenditure with Promotion of Fat Oxidation and Hepatic Lipolysis and Suppressing Hepatic Lipogenesis in <i>db/db</i> Mice |
| title_short | Dietary Nicotinamide Mononucleotide, a Key NAD<sup>+</sup> Intermediate, Alleviates Body Fat Mass and Hypertriglyceridemia by Enhancing Energy Expenditure with Promotion of Fat Oxidation and Hepatic Lipolysis and Suppressing Hepatic Lipogenesis in <i>db/db</i> Mice |
| title_sort | dietary nicotinamide mononucleotide a key nad sup sup intermediate alleviates body fat mass and hypertriglyceridemia by enhancing energy expenditure with promotion of fat oxidation and hepatic lipolysis and suppressing hepatic lipogenesis in i db db i mice |
| topic | NMN obesity dyslipidemia respiratory gas analysis metabolic profile hepatic fatty acid metabolism |
| url | https://www.mdpi.com/2218-1989/15/5/333 |
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