Regulation of glucose metabolism via hepatic forkhead transcription factor 1 (FoxO1) by Morinda citrifolia (noni) in high-fat diet-induced obese mice.
Renewed interest in alternative medicine among diabetic individuals prompted us to investigate anti-diabetic effects of Morinda citrifolia (noni) in high-fat diet (HFD)-fed mice. Type 2 diabetes is associated with increased glucose production due to the inability of insulin to suppress hepatic gluconeogenesis and promote glycolysis. Insulin inhibits gluconeogenesis by modulating transcription factors such as forkhead box O (FoxO1). Based on microarray analysis data, we tested the hypothesis that fermented noni fruit juice (fNJ) improves glucose metabolism via FoxO1 phosphorylation. C57BL/6 male mice were fed a HFD and fNJ for 12 weeks. Body weights and food intake were monitored daily. FoxO1 expression was analysed by real-time PCR and Western blotting. Specificity of fNJ-associated FoxO1 regulation of gluconeogenesis was confirmed by small interfering RNA (siRNA) studies using human hepatoma cells, HepG2. Supplementation with fNJ inhibited weight gain and improved glucose and insulin tolerance and fasting glucose in HFD-fed mice. Hypoglycaemic properties of fNJ were associated with the inhibition of hepatic FoxO1 mRNA expression, with a concomitant increase in FoxO1 phosphorylation and nuclear expulsion of the proteins. Gluconeogenic genes, phosphoenolpyruvate C kinase (PEPCK) and glucose-6-phosphatase (G6P), were significantly inhibited in mice fed a HFD+fNJ. HepG2 cells demonstrated more than 80 % inhibition of PEPCK and G6P mRNA expression in cells treated with FoxO1 siRNA and fNJ. These data suggest that fNJ improves glucose metabolism via FoxO1 regulation in HFD-fed mice.
Laboratory of Metabolic Disorders and Alternative Medicine, Department of Molecular Biosciences and Bioengineering (MBBE), College of Tropical Agriculture and Human Resources (CTAHR), University of Hawaii at Manoa, Honolulu, HI 96822, USA.
Pratibha V
PV
Nerurkar
Laboratory of Metabolic Disorders and Alternative Medicine, Department of Molecular Biosciences and Bioengineering (MBBE), College of Tropical Agriculture and Human Resources (CTAHR), University of Hawaii at Manoa, Honolulu, HI 96822, USA.
Adrienne
A
Nishioka
Laboratory of Metabolic Disorders and Alternative Medicine, Department of Molecular Biosciences and Bioengineering (MBBE), College of Tropical Agriculture and Human Resources (CTAHR), University of Hawaii at Manoa, Honolulu, HI 96822, USA.
Philip O
PO
Eck
Laboratory of Metabolic Disorders and Alternative Medicine, Department of Molecular Biosciences and Bioengineering (MBBE), College of Tropical Agriculture and Human Resources (CTAHR), University of Hawaii at Manoa, Honolulu, HI 96822, USA.
Lisa M
LM
Johns
Retrovirology Research Laboratory, Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA.
Esther
E
Volper
Retrovirology Research Laboratory, Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA.
Vivek R
VR
Nerurkar
D000818:Animals; D001628:Beverages / Q000032:analysis; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005638:Fruit / Q000737:chemistry; D005943:Gluconeogenesis; D006019:Glycolysis; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032066:Morinda / Q000737:chemistry*; D009765:Obesity / Q000097:blood / Q000178:diet therapy / Q000378:metabolism* / Q000503:physiopathology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation
C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D012333:RNA, Messenger