Scutellaria baicalensis Alleviates Insulin Resistance in Diet-Induced Obese Mice by Modulating Inflammation
Abstract
:1. Introduction
2. Results
2.1. Effects of SB on BW and Epididymal Fat and Liver Weight Changes
2.2. Effects of SB on Insulin Resistance and Glucose and Lipid Metabolism
2.3. Effects of SB on Adipose Tissue Macrophages (ATMs) and Liver Kupffer Cells
2.4. Effects of SB on Inflammatory Gene Expression
3. Discussion
4. Materials and Methods
4.1. Preparation of Scutellaria baicalensis (SB)
4.2. Animals and Treatments
4.3. Oral Glucose Tolerance Test (OGTT)
4.4. Oral Fat Tolerance Test (OFTT)
4.5. Biochemical Assays
4.6. RNA Extraction and Analysis of Gene Expression
4.7. Isolation of Stromal Vascular Cells (SVCs) and Liver Immune Cells
4.8. Fluorescence Activated Cell Sorting (FACS) Analysis of Adipose tissue macrophages (ATMs) and Kupffer Cells
4.9. Histological Analyses of Adipose Tissue and Liver
4.10. Statistical Analysis
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Lteif, A.A.; Han, K.; Mather, K.J. Obesity, insulin resistance, and the metabolic syndrome: Determinants of endothelial dysfunction in whites and blacks. Circulation 2005, 112, 32–38. [Google Scholar] [CrossRef] [PubMed]
- Lee, B.C.; Lee, J. Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. Biochim. Biophys. Acta 2014, 1842, 446–462. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, H.; Barnes, G.T.; Yang, Q.; Tan, G.; Yang, D.; Chou, C.J.; Sole, J.; Nichols, A.; Ross, J.S.; Tartaglia, L.A.; Chen, H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Investig. 2003, 112, 1821–1830. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shoelson, S.E.; Herrero, L.; Naaz, A. Obesity, inflammation, and insulin resistance. Gastroenterology 2007, 132, 2169–2180. [Google Scholar] [CrossRef] [PubMed]
- Cai, D.; Yuan, M.; Frantz, D.F.; Melendez, P.A.; Hansen, L.; Lee, J.; Shoelson, S.E. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat. Med. 2005, 11, 183–190. [Google Scholar] [CrossRef] [PubMed]
- Medicine, C.K. Herbology; Yeonglim-sa: Seoul, Korea, 2000; pp. 178–179. [Google Scholar]
- Yoon, S.B.; Lee, Y.J.; Park, S.K.; Kim, H.C.; Bae, H.; Kim, H.M.; Ko, S.G.; Choi, H.Y.; Oh, M.S.; Park, W. Anti-inflammatory effects of Scutellaria baicalensis water extract on LPS-activated RAW 264.7 macrophages. J. Ethnopharmacol. 2009, 125, 286–290. [Google Scholar] [CrossRef] [PubMed]
- Kim, O.S.; Seo, C.S.; Kim, Y.; Shin, H.K.; Ha, H. Extracts of Scutellariae Radix inhibit low-density lipoprotein oxidation and the lipopolysaccharide-induced macrophage inflammatory response. Mol. Med. Rep. 2015, 12, 1335–1341. [Google Scholar] [CrossRef] [PubMed]
- Song, K.H.; Lee, S.H.; Kim, B.Y.; Park, A.Y.; Kim, J.Y. Extracts of Scutellaria baicalensis reduced body weight and blood triglyceride in db/db Mice. Phytother. Res. 2013, 27, 244–250. [Google Scholar] [CrossRef] [PubMed]
- Chen, Q.; Liu, M.; Yu, H.; Li, J.; Wang, S.; Zhang, Y.; Qiu, F.; Wang, T. Scutellaria baicalensis regulates FFA metabolism to ameliorate NAFLD through the AMPK-mediated SREBP signaling pathway. J. Nat. Med. 2018, 72, 655–666. [Google Scholar] [CrossRef] [PubMed]
- Scherer, P.E. Adipose tissue: From lipid storage compartment to endocrine organ. Diabetes 2006, 55, 1537–1545. [Google Scholar] [CrossRef] [PubMed]
- Fried, S.K.; Bunkin, D.A.; Greenberg, A.S. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: Depot difference and regulation by glucocorticoid. J. Clin. Endocrinol. Metab. 1998, 83, 847–850. [Google Scholar] [CrossRef]
- Guo, H.X.; Liu, D.H.; Ma, Y.; Liu, J.F.; Wang, Y.; Du, Z.Y.; Wang, X.; Shen, J.K.; Peng, H.L. Long-term baicalin administration ameliorates metabolic disorders and hepatic steatosis in rats given a high-fat diet. Acta Pharmacol. Sin. 2009, 30, 1505–1512. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bak, E.J.; Kim, J.; Choi, Y.H.; Kim, J.H.; Lee, D.E.; Woo, G.H.; Cha, J.H.; Yoo, Y.J. Wogonin ameliorates hyperglycemia and dyslipidemia via PPARalpha activation in db/db mice. Clin. Nutr. 2014, 33, 156–163. [Google Scholar] [CrossRef] [PubMed]
- Pu, P.; Wang, X.A.; Salim, M.; Zhu, L.H.; Wang, L.; Chen, K.J.; Xiao, J.F.; Deng, W.; Shi, H.W.; Jiang, H.; et al. Baicalein, a natural product, selectively activating AMPKalpha(2) and ameliorates metabolic disorder in diet-induced mice. Mol. Cell Endocrinol. 2012, 362, 128–138. [Google Scholar] [CrossRef] [PubMed]
- Eckel, R.H.; Grundy, S.M.; Zimmet, P.Z. The metabolic syndrome. Lancet 2005, 365, 1415–1428. [Google Scholar] [CrossRef]
- Kahn, B.B.; Flier, J.S. Obesity and insulin resistance. J. Clin. Investig. 2000, 106, 473–481. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cornier, M.A.; Dabelea, D.; Hernandez, T.L.; Lindstrom, R.C.; Steig, A.J.; Stob, N.R.; Van Pelt, R.E.; Wang, H.; Eckel, R.H. The metabolic syndrome. Endocrine Rev. 2008, 29, 777–822. [Google Scholar] [CrossRef] [PubMed]
- Ginsberg, H.N.; Zhang, Y.L.; Hernandez-Ono, A. Regulation of plasma triglycerides in insulin resistance and diabetes. Arch. Med. Res. 2005, 36, 232–240. [Google Scholar] [CrossRef]
- Matsuo, Y.; Matsumoto, K.; Inaba, N.; Mimaki, Y. Daisaikoto Inhibits Pancreatic Lipase Activity and Decreases Serum Triglyceride Levels in Mice. Biol. Pharma. Bull. 2018, 41, 1485–1488. [Google Scholar] [CrossRef]
- Altintas, M.M.; Azad, A.; Nayer, B.; Contreras, G.; Zaias, J.; Faul, C.; Reiser, J.; Nayer, A. Mast cells, macrophages, and crown-like structures distinguish subcutaneous from visceral fat in mice. J. Lipid Res. 2011, 52, 480–488. [Google Scholar] [CrossRef]
- Makki, K.; Froguel, P.; Wolowczuk, I. Adipose tissue in obesity-related inflammation and insulin resistance: Cells, cytokines, and chemokines. ISRN Inflamm. 2013, 2013, 139239. [Google Scholar] [CrossRef] [PubMed]
- Fu, Y.; Luo, J.; Jia, Z.; Zhen, W.; Zhou, K.; Gilbert, E.; Liu, D. Baicalein Protects against Type 2 Diabetes via Promoting Islet beta-Cell Function in Obese Diabetic Mice. Int. J. Endocrinol. 2014, 2014, 846742. [Google Scholar] [CrossRef] [PubMed]
- Chawla, A.; Nguyen, K.D.; Goh, Y.P. Macrophage-mediated inflammation in metabolic disease. Nat. Rev. Immunol. 2011, 11, 738–749. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bays, H.E.; Gonzalez-Campoy, J.M.; Bray, G.A.; Kitabchi, A.E.; Bergman, D.A.; Schorr, A.B.; Rodbard, H.W.; Henry, R.R. Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity. Expert Rev. Cardiovas. Ther. 2008, 6, 343–368. [Google Scholar] [CrossRef] [PubMed]
- Bahceci, M.; Gokalp, D.; Bahceci, S.; Tuzcu, A.; Atmaca, S.; Arikan, S. The correlation between adiposity and adiponectin, tumor necrosis factor alpha, interleukin-6 and high sensitivity C-reactive protein levels. Is adipocyte size associated with inflammation in adults? J. Endocrinol. Investig. 2007, 30, 210–214. [Google Scholar] [CrossRef]
- Weisberg, S.P.; McCann, D.; Desai, M.; Rosenbaum, M.; Leibel, R.L.; Ferrante, A.W., Jr. Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Investig. 2003, 112, 1796–1808. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kinoshita, M.; Uchida, T.; Sato, A.; Nakashima, M.; Nakashima, H.; Shono, S.; Habu, Y.; Miyazaki, H.; Hiroi, S.; Seki, S. Characterization of two F4/80-positive Kupffer cell subsets by their function and phenotype in mice. J. Hepatol. 2010, 53, 903–910. [Google Scholar] [CrossRef]
- Lanthier, N.; Molendi-Coste, O.; Horsmans, Y.; van Rooijen, N.; Cani, P.D.; Leclercq, I.A. Kupffer cell activation is a causal factor for hepatic insulin resistance. Am. J. Physiol. Gastrointest. Liver Physiol. 2010, 298, G107–G116. [Google Scholar] [CrossRef]
- Nathan, C.F.; Murray, H.W.; Wiebe, M.E.; Rubin, B.Y. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J. Exp. Med. 1983, 158, 670–689. [Google Scholar] [CrossRef] [Green Version]
- Tarantino, G.; Costantini, S.; Citro, V.; Conforti, P.; Capone, F.; Sorice, A.; Capone, D. Interferon-alpha 2 but not Interferon-gamma serum levels are associated with intramuscular fat in obese patients with nonalcoholic fatty liver disease. J. Transl. Med. 2019, 17, 8. [Google Scholar] [CrossRef]
- Parekh, P.I.; Petro, A.E.; Tiller, J.M.; Feinglos, M.N.; Surwit, R.S. Reversal of diet-induced obesity and diabetes in C57BL/6J mice. Metabolism 1998, 47, 1089–1096. [Google Scholar] [CrossRef]
- Yun, J.; Jung, Y.S. A Scutellaria baicalensis radix water extract inhibits morphine-induced conditioned place preference. Pharm. Biol. 2014, 52, 1382–1387. [Google Scholar] [CrossRef] [PubMed]
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Na, H.-Y.; Lee, B.-C. Scutellaria baicalensis Alleviates Insulin Resistance in Diet-Induced Obese Mice by Modulating Inflammation. Int. J. Mol. Sci. 2019, 20, 727. https://doi.org/10.3390/ijms20030727
Na H-Y, Lee B-C. Scutellaria baicalensis Alleviates Insulin Resistance in Diet-Induced Obese Mice by Modulating Inflammation. International Journal of Molecular Sciences. 2019; 20(3):727. https://doi.org/10.3390/ijms20030727
Chicago/Turabian StyleNa, Hyun-Young, and Byung-Cheol Lee. 2019. "Scutellaria baicalensis Alleviates Insulin Resistance in Diet-Induced Obese Mice by Modulating Inflammation" International Journal of Molecular Sciences 20, no. 3: 727. https://doi.org/10.3390/ijms20030727