Administration of Nicotinamide Mononucleotide (NMN) Reduces Metabolic Impairment in Male Mouse Offspring from Obese Mothers.

Neil A Youngson,Sabiha S Chowdhury,Christopher Hagan,Golam M Uddin,David A Sinclair,Margaret J Morris

doi:10.3390/cells9040791

Neil A Youngson, Sabiha S Chowdhury + Show 4 more

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https://doi.org/10.3390/cells9040791

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Journal: Cells	Publication Date: Mar 25, 2020
Citations: 23	License type: CC BY 4.0

Affiliation: UNSW Sydney, Harvard University

Abstract

Maternal obesity impacts offspring metabolism. We sought to boost mitochondrial energy metabolism using the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) to treat metabolic impairment induced by maternal and long-term post weaning over-nutrition. Male offspring of lean or obese mothers, fed chow or high fat diet (HFD) for 30 weeks post-weaning, were given NMN injection, starting at 31 weeks of age, daily for 3 weeks before sacrifice. Glucose tolerance was tested at 10, 29 and 32 weeks of age to measure short and long term effects of post-weaning HFD, and NMN treatment. Plasma insulin and triglycerides, liver triglycerides and expression of mitochondrial metabolism-related genes were measured at 34 weeks. Impaired glucose tolerance due to maternal and post weaning HFD was significantly improved by only 8 days of NMN treatment. Furthermore, in offspring of obese mothers hepatic lipid accumulation was reduced due to NMN treatment by 50% and 23% in chow and HFD fed offspring respectively. Hepatic genes involved in fat synthesis, transport and uptake were reduced, while those involved in fatty acid oxidation were increased by NMN. Overall this finding suggests short term administration of NMN could be a therapeutic approach for treating metabolic disease due to maternal and post weaning over-nutrition, even in late adulthood.

Highlights

Prior to the end of the 19th century, health concerns in developed countries were largely focused on poverty, malnutrition, and communicable diseases
We demonstrated that only 18 days of nicotinamide mononucleotide (NMN) injection improved glucose tolerance, reduced lipid accumulation and upregulated genes responsible for fatty acid metabolism in female offspring of obese mothers [18]
The impact of maternal obesity was exacerbated in those pups eating high fat diet (HFD); a significant interaction between maternal and post-weaning diet was observed

Summary

Introduction

Prior to the end of the 19th century, health concerns in developed countries were largely focused on poverty, malnutrition, and communicable diseases. At the beginning of the 21st century, the World Health Organization (WHO) considers obesity to be a major health problem [1]. As with obesity in adults, the prevalence of childhood obesity is rising across the world [2]. Childhood obesity can lead to serious complications and lifelong diseases like cardiac disorders, type 2 diabetes (T2D), psychological complications, pulmonary disorders, and exercise intolerance [3]. Parental overweight (body mass index (BMI) > 25) is considered as a key contributor to the risk of being overweight or obese in early life [4]. It has been reported that early life developmental issues strongly associate with the prevalence of obesity and related metabolic disorders later in life [5,6]. Extensive evidence links increased maternal BMI to adverse offspring metabolic and cardiovascular outcomes, Cells 2020, 9, 791; doi:10.3390/cells9040791 www.mdpi.com/journal/cells

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