Protective effect of vanillic acid against hyperinsulinemia, hyperglycemia and hyperlipidemia via alleviating hepatic insulin resistance and inflammation in High-Fat Diet (HFD)-fed rats

Wen Chang Chang, James Swi Bea Wu, Chen Wen Chen, Po Ling Kuo, Hsu Min Chien, Yuh Tai Wang, Szu Chuan Shen

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Excess free fatty acid accumulation from abnormal lipid metabolism results in the insulin resistance in peripheral cells, subsequently causing hyperinsulinemia, hyperglycemia and/or hyperlipidemia in diabetes mellitus (DM) patients. Herein, we investigated the effect of phenolic acids on glucose uptake in an insulin-resistant cell-culture model and on hepatic insulin resistance and inflammation in rats fed a high-fat diet (HFD). The results show that vanillic acid (VA) demonstrated the highest glucose uptake ability among all tested phenolic acids in insulin-resistant FL83B mouse hepatocytes. Furthermore, rats fed HFD for 16 weeks were orally administered with VA daily (30 mg/kg body weight) at weeks 13–16. The results show that levels of serum insulin, glucose, triglyceride, and free fatty acid were significantly decreased in VA-treated HFD rats (p< 0.05), indicating the protective effects of VA against hyperinsulinemia, hyperglycemia and hyperlipidemia in HFD rats. Moreover, VA significantly reduced values of area under the curve for glucose (AUCglucose) in oral glucose tolerance test and homeostasis model assessment-insulin resistance (HOMA-IR) index, suggesting the improving effect on glucose tolerance and insulin resistance in HFD rats. The Western blot analysis revealed that VA significantly up-regulated expression of hepatic insulin-signaling and lipid metabolism-related protein, including insulin receptor, phosphatidylinositol-3 kinase, glucose transporter 2, and phosphorylated acetyl CoA carboxylase in HFD rats. VA also significantly down-regulated hepatic inflammation-related proteins, including cyclooxygenase-2 and monocyte chemoattractant protein-1 expressions in HFD rats. These results indicate that VA might ameliorate insulin resistance via improving hepatic insulin signaling and alleviating inflammation pathways in HFD rats. These findings also suggest the potential of VA in preventing the progression of DM.

Original languageEnglish
Pages (from-to)9946-9959
Number of pages14
JournalNutrients
Volume7
Issue number12
DOIs
Publication statusPublished - Dec 2 2015
Externally publishedYes

Fingerprint

Vanillic Acid
vanillic acid
hyperinsulinemia
Hyperinsulinism
High Fat Diet
hyperlipidemia
hyperglycemia
high fat diet
Hyperlipidemias
insulin resistance
Hyperglycemia
protective effect
Insulin Resistance
inflammation
Inflammation
liver
Liver
rats
Insulin
Glucose

Keywords

  • Hyperglycemia
  • Hyperinsulinemia
  • Hyperlipidemia
  • Insulin resistance
  • Vanillic acid

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

Cite this

Protective effect of vanillic acid against hyperinsulinemia, hyperglycemia and hyperlipidemia via alleviating hepatic insulin resistance and inflammation in High-Fat Diet (HFD)-fed rats. / Chang, Wen Chang; Wu, James Swi Bea; Chen, Chen Wen; Kuo, Po Ling; Chien, Hsu Min; Wang, Yuh Tai; Shen, Szu Chuan.

In: Nutrients, Vol. 7, No. 12, 02.12.2015, p. 9946-9959.

Research output: Contribution to journalArticle

Chang, Wen Chang ; Wu, James Swi Bea ; Chen, Chen Wen ; Kuo, Po Ling ; Chien, Hsu Min ; Wang, Yuh Tai ; Shen, Szu Chuan. / Protective effect of vanillic acid against hyperinsulinemia, hyperglycemia and hyperlipidemia via alleviating hepatic insulin resistance and inflammation in High-Fat Diet (HFD)-fed rats. In: Nutrients. 2015 ; Vol. 7, No. 12. pp. 9946-9959.
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AU - Chen, Chen Wen

AU - Kuo, Po Ling

AU - Chien, Hsu Min

AU - Wang, Yuh Tai

AU - Shen, Szu Chuan

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AB - Excess free fatty acid accumulation from abnormal lipid metabolism results in the insulin resistance in peripheral cells, subsequently causing hyperinsulinemia, hyperglycemia and/or hyperlipidemia in diabetes mellitus (DM) patients. Herein, we investigated the effect of phenolic acids on glucose uptake in an insulin-resistant cell-culture model and on hepatic insulin resistance and inflammation in rats fed a high-fat diet (HFD). The results show that vanillic acid (VA) demonstrated the highest glucose uptake ability among all tested phenolic acids in insulin-resistant FL83B mouse hepatocytes. Furthermore, rats fed HFD for 16 weeks were orally administered with VA daily (30 mg/kg body weight) at weeks 13–16. The results show that levels of serum insulin, glucose, triglyceride, and free fatty acid were significantly decreased in VA-treated HFD rats (p< 0.05), indicating the protective effects of VA against hyperinsulinemia, hyperglycemia and hyperlipidemia in HFD rats. Moreover, VA significantly reduced values of area under the curve for glucose (AUCglucose) in oral glucose tolerance test and homeostasis model assessment-insulin resistance (HOMA-IR) index, suggesting the improving effect on glucose tolerance and insulin resistance in HFD rats. The Western blot analysis revealed that VA significantly up-regulated expression of hepatic insulin-signaling and lipid metabolism-related protein, including insulin receptor, phosphatidylinositol-3 kinase, glucose transporter 2, and phosphorylated acetyl CoA carboxylase in HFD rats. VA also significantly down-regulated hepatic inflammation-related proteins, including cyclooxygenase-2 and monocyte chemoattractant protein-1 expressions in HFD rats. These results indicate that VA might ameliorate insulin resistance via improving hepatic insulin signaling and alleviating inflammation pathways in HFD rats. These findings also suggest the potential of VA in preventing the progression of DM.

KW - Hyperglycemia

KW - Hyperinsulinemia

KW - Hyperlipidemia

KW - Insulin resistance

KW - Vanillic acid

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