title: Nicotinamide improves glucose metabolism and affects the hepatic NAD-sirtuin pathway in a rodent model of obesity and type 2 diabetes.
abstract: Nicotinic acid (NA) and nicotinamide (NAM) are major forms of niacin and exert their physiological functions as precursors of nicotinamide adenine dinucleotide (NAD). Sirtuins, which are NAD-dependent deacetylases, regulate glucose and lipid metabolism and are implicated in the pathophysiology of aging, diabetes, and hepatic steatosis. The aim of this study was to investigate the effects of two NAD donors, NA and NAM, on glucose metabolism and the hepatic NAD-sirtuin pathway. The effects were investigated in OLETF rats, a rodent model of obesity and type 2 diabetes. OLETF rats were divided into five groups: (1) high fat (HF) diet, (2) HF diet and 10 mg NA/kg body weight (BW)/day (NA 10), (3) HF diet and 100 mg NA/kg BW/day (NA 100), (4) HF diet and 10 mg NAM/kg BW/day (NAM 10), and (5) HF diet and 100 mg NAM/kg BW/day (NAM 100). NA and NAM were delivered via drinking water for four weeks. NAM 100 treatment affected glucose control significantly, as shown by lower levels of accumulative area under the curve during oral glucose tolerance test, serum fasting glucose, serum fasting insulin, and homeostasis model assessment of insulin resistance, and higher levels of serum adiponectin. With regard to NAD-sirtuin pathway, intracellular nicotinamide phosphoribosyltransferase, NAD, the NAD/NADH ratio, Sirt1, 2, 3, and 6 mRNA expressions, and Sirt1 activity all increased in livers of NAM 100-treated rats. These alterations were accompanied by the increased levels of proliferator-activated receptor gamma, coactivator 1 alpha and mitochondrial DNA. The effect of NA treatment was less evident than that of NAM 100. These results demonstrate that NAM is more effective than NA on the regulation of glucose metabolism and the NAD-sirtuin pathway, which may relate to the altered mitochondrial biogenesis.
authors: Department of Food and Nutrition and Human Ecology Research Institute, Chonnam National University, Gwangju, South Korea.
authors: Soo Jin
authors: SJ
authors: Yang
authors: Jung Mook
authors: JM
authors: Choi
authors: Lisa
authors: L
authors: Kim
authors: Se Eun
authors: SE
authors: Park
authors: Eun Jung
authors: EJ
authors: Rhee
authors: Won Young
authors: WY
authors: Lee
authors: Ki Won
authors: KW
authors: Oh
authors: Sung Woo
authors: SW
authors: Park
authors: Cheol-Young
authors: CY
authors: Park
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D063269:Mitochondrial Turnover / Q000187:drug effects; D009243:NAD / Q000378:metabolism*; D009536:Niacinamide / Q000494:pharmacology*; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D051381:Rats; D020334:Rats, Inbred OLETF; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; D009243:NAD; D009536:Niacinamide; D054409:Nicotinamide Phosphoribosyltransferase; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D037761:Sirtuins; D005947:Glucose
keywords: NAD; Nicotinamide; Nicotinic acid; PGC-1 alpha; Sirtuin