{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:33:31Z","timestamp":1784759611554,"version":"3.55.0"},"reference-count":53,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2015,12,2]],"date-time":"2015-12-02T00:00:00Z","timestamp":1449014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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\u201316. The results show that levels of serum insulin, glucose, triglyceride, and free fatty acid were significantly decreased in VA-treated HFD rats (p &lt; 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.<\/jats:p>","DOI":"10.3390\/nu7125514","type":"journal-article","created":{"date-parts":[[2015,12,2]],"date-time":"2015-12-02T10:44:27Z","timestamp":1449053067000},"page":"9946-9959","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":106,"title":["Protective Effect of Vanillic Acid against Hyperinsulinemia, Hyperglycemia and Hyperlipidemia via Alleviating Hepatic Insulin Resistance and Inflammation in High-Fat Diet (HFD)-Fed Rats"],"prefix":"10.3390","volume":"7","author":[{"given":"Wen-Chang","family":"Chang","sequence":"first","affiliation":[{"name":"Graduate Institute of Food Science and Technology, National Taiwan University, P.O. Box 23-14, Taipei 10672, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Wu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Food Science and Technology, National Taiwan University, P.O. Box 23-14, Taipei 10672, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Food Science and Technology, National Taiwan University, P.O. Box 23-14, Taipei 10672, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Ling","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Human Development and Family Studies, National Taiwan Normal University, No. 162, Sec. 1, Heping East Road, Taipei 10610, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsu-Min","family":"Chien","sequence":"additional","affiliation":[{"name":"Department of Nursing, Taipei City Hospital, Renai Branch, No. 10, Sec. 4, Renai Road, Taipei 10629, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuh-Tai","family":"Wang","sequence":"additional","affiliation":[{"name":"Life Science Center, Hsing Wu Institute of Technology, No. 101, Sec. 1, Fen-Liao Road, Lin-Kou District, New Taipei City 244, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szu-Chuan","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Human Development and Family Studies, National Taiwan Normal University, No. 162, Sec. 1, Heping East Road, Taipei 10610, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,12,2]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization Preventing Diabetes is Essential for Keeping Health and Well-Being in Tajikistan. 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