Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Metabolic effects of chronic dihydronicotinamide riboside (NRH) administration in mice - Microbiome 16S rRNA sequencing of murine feces (NRH treatment)

ABSTRACT: NAD+ is a crucial cofactor for the activity of various enzymes, including sirtuins and ADP-ribosyl transferases, and its decline is associated with aging and metabolic-related diseases. Therefore, a strong interest has been raised in the therapeutic use of NAD+ precursors (Vitamin B3s), but many suffer from poor bioavailability and adverse effects. This study characterizes the metabolic impact of dihydronicotinamide riboside, a recently identified novel form of NAD+ precursor. Upon oral administration in mice, NRH reaches all tissues examined. Chronic administration in low-fat diet-fed mice showed negligible metabolic effects, while high-fat diet-fed mice were protected against body weight gain and glucose intolerance. However, our study also unveiled potential side effects at higher doses. Thus, NRH could constitute an alternative NAD+ boosting strategy to prevent diet-induced metabolic complications and conditions associated with low NAD+ levels, but the therapeutic window must be optimized to maximize benefits and minimize risks.

INSTRUMENT(S): Illumina MiSeq

ORGANISM(S): Mus musculus

SUBMITTER: Marie Rumpler

PROVIDER: E-MTAB-14177 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Obesity is associated with a chronic, low-grade, systemic inflammation that may contribute to the development of insulin resistance and type 2 diabetes. Resveratrol, a natural compound with anti-inflammatory properties, is shown to improve glucose tolerance and insulin sensitivity in obese mice and humans. Here we tested the effect of a 2-year resveratrol administration on the pro-inflammatory profile and insulin resistance caused by a high-fat, high-sugar (HFS) diet in white adipose tissue (WAT) from rhesus monkeys. Eighty mg/day of resveratrol for 12-month followed by 480 mg/day for the second year decreased adipocyte size, increased sirtuin 1 expression, decreased NF-kB activation and improved insulin sensitivity in visceral but not subcutaneous WAT from HFS-fed animals. These effects were reproduced in 3T3-L1 adipocytes cultured in media supplemented with serum from monkeys fed HFS +/- resveratrol diets. In conclusion, chronic administration of resveratrol exerts beneficial metabolic and inflammatory adaptations in visceral WAT from diet-induced obese monkeys. Twenty-four adult (7-13 years old) male rhesus monkeys (Macaca mulatta) were housed individually in standard nonhuman primate caging on a 12h light/12h dark cycle, room temperature (78 +/- 2 degrees F), and humidity at 60 +/- 20%. One pairing was maintained throughout the study; all other monkeys had extensive visual, auditory, and olfactory but limited tactile contact with monkeys housed in the same room. Monkeys received 2 meals per day at estimated ad libitum levels throughout the study. Water was always available ad libitum. Monkeys were monitored minimally 3 times daily by trained animal care staff. During baseline assessments, all monkeys were maintained on a commercially available closed formula monkey chow. After baseline assessment, four male rhesus monkeys remained on the healthy standard diet (SD), 10 male rhesus monkeys were begun on a high fat/high sucrose (HFS) diet and 10 male rhesus monkeys were begun on a high fat/high sucrose (HFS) diet plus Resveratrol, 80mg/day. After one year of dietary intervention, the amount of resveratrol was increased to 480mg/day for one additional year. Tissues were then harvested for the array experiments.

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Metabolic effects of chronic dihydronicotinamide riboside (NRH) administration in mice - Microbiome 16S rRNA sequencing of murine feces (NRH treatment)

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