title: Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes.
abstract: Low-grade chronic inflammation (metaflammation) is a major contributing factor for the onset and development of metabolic diseases, such as type 2 diabetes, obesity, and cardiovascular disease. Nicotinamide riboside (NR), which is present in milk and beer, is a functional vitamin B3 having advantageous effects on metabolic regulation. However, the anti-inflammatory capacity of NR is unknown. This study evaluated whether NR modulates hepatic nucleotide binding and oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Male, 8-week-old KK/HlJ mice were allocated to the control or NR group. NR (100 mg/kg/day) or vehicle (phosphate-buffered saline) was administrated by an osmotic pump for 7 days. Glucose control, lipid profiles, NLRP3 inflammasome, and inflammation markers were analyzed, and structural and histological analyses were conducted. NR treatment did not affect body weight gain, food intake, and liver function. Glucose control based on the oral glucose tolerance test and levels of serum insulin and adiponectin was improved by NR treatment. Among tested lipid profiles, NR lowered the total cholesterol concentration in the liver. Histological and structural analysis by hematoxylin and eosin staining and transmission electron microscopy, respectively, showed that NR rescued the disrupted cellular integrity of the mitochondria and nucleus in the livers of obese and diabetic KK mice. In addition, NR treatment significantly improved hepatic proinflammatory markers, including tumor necrosis factor-alpha, interleukin (IL)-6, and IL-1. These ameliorations were accompanied by significant shifts of NLRP3 inflammasome components (NLRP3, ASC, and caspase1). These results demonstrate that NR attenuates hepatic metaflammation by modulating the NLRP3 inflammasome.
authors.affiliation: 1 Division of Food and Nutrition, Human Ecology Research Institute, Chonnam National University , Gwangju, Korea.
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: 1 Division of Food and Nutrition, Human Ecology Research Institute, Chonnam National University , Gwangju, Korea.
authors.forename: Young-Shick
authors.initials: YS
authors.lastname: Hong
authors.affiliation: 1 Division of Food and Nutrition, Human Ecology Research Institute, Chonnam National University , Gwangju, Korea.
authors.forename: Woojin
authors.initials: W
authors.lastname: Jun
authors.affiliation: 2 Department of Food and Nutrition, Seoul Women's University , Seoul, Korea.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Yang
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy*; D007328:Insulin / Q000097:blood; D053583:Interleukin-1beta / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011726:Pyridinium Compounds; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014803:Vitamin B Complex / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D052242:Adiponectin; D000893:Anti-Inflammatory Agents; D051017:Apoptosis Regulatory Proteins; D001786:Blood Glucose; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D058847:Inflammasomes; D007328:Insulin; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C498534:Pycard protein, mouse; D011726:Pyridinium Compounds; D014409:Tumor Necrosis Factor-alpha; C018613:nicotinamide-beta-riboside; D014803:Vitamin B Complex; D009536:Niacinamide; D002784:Cholesterol; D020170:Caspase 1
keywords: NLRP3 inflammasome; hepatic metaflammation; nicotinamide riboside