Caulis Spatholobi Ameliorates Obesity through Activating Brown Adipose Tissue and Modulating the Composition of Gut Microbiota
Abstract
:1. Introduction
2. Results
2.1. WECS Ameliorates Obesity in DIO Mice
2.2. WECS Augments Whole-Body Energy Metabolism
2.3. WECS Induces BAT Activity and Beige Generation in sWAT
2.4. WECS Increases Mitochondrial Biogenesis And Oxygen Consumption
2.5. WECS Improves Glucose Homeostasis and Insulin Resistance
2.6. WECS Relieves Hepatic Steatosis
2.7. WECS Modulated the Composition of the Gut Microbiota
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Glucose Tolerance Test and Insulin Tolerance Test
4.3. Rectal Temperature and Energy Expenditure
4.4. Metabolic Rate and Physical Activity
4.5. Body Composition Measurements
4.6. PET-CT Imaging
4.7. Histology and BODIPY Staining
4.8. Gut Microbiota Analysis
4.9. Brown Adipocyte Differentiation
4.10. Measurements of Cellular Respiration
4.11. Quantitative Real-Time PCR
4.12. Western Blot Analysis
4.13. Immunofluorescence Staining
4.14. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
- Ng, M.; Fleming, T.; Robinson, M.; Thomson, B.; Graetz, N.; Margono, C.; Mullany, E.C.; Biryukov, S.; Abbafati, C.; Abera, S.F.; et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014, 384, 766–781. [Google Scholar] [CrossRef]
- Jin, W.Z.; Patti, M.E. Genetic determinants and molecular pathways in the pathogenesis of Type 2 diabetes. Clin. Sci. 2009, 116, 99–111. [Google Scholar] [CrossRef] [PubMed]
- Lowell, B.B.; Spiegelman, B.M. Towards a molecular understanding of adaptive thermogenesis. Nature 2000, 404, 652–660. [Google Scholar] [CrossRef] [PubMed]
- Ravussin, E.; Galgani, J.E. The implication of brown adipose tissue for humans. Annu. Rev. Nutr. 2011, 31, 33–47. [Google Scholar] [CrossRef] [PubMed]
- Tseng, Y.H.; Cypess, A.M.; Kahn, C.R. Cellular bioenergetics as a target for obesity therapy. Nat. Rev. Drug Discov. 2010, 9, 465–482. [Google Scholar] [CrossRef] [Green Version]
- Harms, M.; Seale, P. Brown and beige fat: Development, function and therapeutic potential. Nat. Med. 2013, 19, 1252–1263. [Google Scholar] [CrossRef]
- Kajimura, S.; Spiegelman, B.M.; Seale, P. Brown and beige fat: Physiological roles beyond heat generation. Cell Metab. 2015, 22, 546–559. [Google Scholar] [CrossRef]
- Van Marken Lichtenbelt, W.D.; Vanhommerig, J.W.; Smulders, N.M.; Drossaerts, J.M.; Kemerink, G.J.; Bouvy, N.D.; Schrauwen, P.; Teule, G.J. Cold-activated brown adipose tissue in healthy men. N. Engl. J. Med. 1944, 360, 1500–1508. [Google Scholar] [CrossRef]
- Virtanen, K.; Lidell, M.J.; Heglind, M.; Westergren, R.; Niemi, T.; Taittonen, M.; Laine, J.; Savisto, N.; Enerback, S.; Nuutila, P. Functional brown adipose tissue in healthy adults. N. Engl. J. Med. 2009, 360, 1518–1525. [Google Scholar] [CrossRef]
- Kajimura, S.; Seale, P.; Spiegelman, B.M. Transcriptional control of brown fat development. Cell Metab. 2010, 11, 257–262. [Google Scholar] [CrossRef]
- Kajimura, S.; Seale, P.; Kubota, K.; Lunsford, E.; Frangioni, J.V.; Gygi, S.P.; Spiegelman, B.M. Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature 2009, 460, 1154–1158. [Google Scholar] [CrossRef] [PubMed]
- Boström, P.; Wu, J.; Jedrychowski, M.P.; Korde, A.; Ye, L.; Lo, J.C.; Rasbach, K.A.; Boström, E.A.; Choi, J.H.; Long, J.Z. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012, 481, 463–468. [Google Scholar] [CrossRef] [PubMed]
- Ridaura, V.K.; Faith, J.J.; Rey, F.E.; Cheng, J.; Duncan, A.E.; Kau, A.L.; Griffin, N.W.; Lombard, V.; Henrissat, B.; Bain, J.R.; et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 2013, 341, 1241214. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.J.; Li, S.; Gan, R.Y.; Zhou, T.; Xu, D.P.; Li, H.B. Impacts of gut bacteria on human health and diseases. Int. J. Mol. Sci. 2015, 16, 7493–7519. [Google Scholar] [CrossRef] [PubMed]
- Chang, C.J.; Lin, C.S.; Lu, C.C.; Martel, J.; Ko, Y.F.; Ojcius, D.M.; Tseng, S.F.; Wu, T.R.; Chen, Y.Y.; Young, J.D. Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota. Nat. Commun. 2015, 6, 7489. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gong, T.; Wang, D.X.; Chen, R.Y.; Liu, P.; Yu, D.Q. Novel benzil and isoflavone derivatives from Millettia dielsiana. Planta Medica. 2009, 75, 236–242. [Google Scholar] [CrossRef]
- Chen, S.R.; Wang, A.Q.; Lin, L.G.; Qiu, H.C.; Wang, Y.T.; Wang, Y. In Vitro Study on Anti-Hepatitis C Virus Activity of Spatholobus suberectus Dunn. Molecules 2016, 21, 1367. [Google Scholar] [CrossRef]
- Wang, Z.; Wang, D.; Han, S.; Wang, N.; Mo, F.; Loo, T.Y.; Shen, J.; Huang, H.; Chen, J. Bioactivity-Guided Identification and Cell Signaling Technology to Delineate the Lactate Dehydrogenase A Inhibition Effects of Spatholobus suberectus on Breast Cancer. PLoS ONE 2013, 8, e56631. [Google Scholar] [CrossRef]
- Sun, J.Q.; Zhang, G.L.; Zhang, Y.; Nan, N.; Sun, X.; Yu, M.W.; Wang, H.; Li, J.P.; Wang, X.M. Spatholobus suberectus Column Extract Inhibits Estrogen Receptor Positive Breast Cancer via Suppressing ER MAPK PI3K/AKT Pathway. Evidence-Based Complement. Alter. Med. 2016, 2016, 1–13. [Google Scholar]
- Lee, M.H.; Lin, Y.P.; Hsu, F.L.; Zhan, G.R.; Yen, K.Y. Bioactive constituents of Spatholobus suberectus in regulating tyrosinase-related proteins and mRNA in HEMn cells. Phytochemistry 2006, 67, 1262–1270. [Google Scholar] [CrossRef]
- Crane, J.D.; Palanivel, R.; Mottillo, E.P.; Bujak, A.L.; Wang, H.; Ford, R.J.; Collins, A.; Blumer, R.M.; Fullerton, M.D.; Yabut, J.M.; et al. Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis. Nat. Med. 2015, 21, 166–172. [Google Scholar] [CrossRef] [PubMed]
- Kooijman, S.; van den Heuvel, J.K.; Rensen, P.C.N. Neuronal Control of Brown Fat Activity. Trends Endocrinol. Metab. 2015, 26, 657–668. [Google Scholar] [CrossRef] [PubMed]
- Ren, C.; Zhang, Y.; Cui, W.; Lu, G.; Wang, Y.; Gao, H.; Huang, L.; Mu, Z. A polysaccharide extract of mulberry leaf ameliorates hepatic glucose metabolism and insulin signaling in rats with type 2 diabetes induced by high fat-diet and streptozotocin. Int. J. Biol Macromol. 2015, 72, 951–959. [Google Scholar] [CrossRef] [PubMed]
- Jeszka-Skowron, M.; Flaczyk, E.; Jeszka, J.; Krejpcio, Z.; Król, E.; Buchowski, M.S. Mulberry leaf extract intake reduces hyperglycaemia in streptozotocin (STZ)-induced diabetic rats fed high-fat diet. J. Funct. Foods 2014, 8, 9–17. [Google Scholar] [CrossRef]
- Liu, P.; Wang, D.X.; Chen, G.Y.; Chen, M.L. Effect of compounds extracted from spatholobus suberectus dunn on the proliferation of hematopoietic progenitor cell. Chin. Pharmacol. Bull. 2007, 23, 741–745. [Google Scholar]
- Kahn, S.E.; Hull, R.L.; Utzschneider, K.M. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006, 444, 840–846. [Google Scholar] [CrossRef]
- Sumara, G.; Formentini, I.; Collins, S.; Sumara, I.; Windak, R.; Bodenmiller, B.; Ramracheya, R.; Caille, D.; Jiang, H.; Platt, K.A. Regulation of PKD by the MAPK p38δ in Insulin Secretion and Glucose Homeostasis. Cell 2009, 136, 235–248. [Google Scholar] [CrossRef]
- Hand, G.A. Top 10 Research Questions Related to Energy Balance. Res. Q. Exerc. Sport. 2015, 85, 49–58. [Google Scholar]
- Zingaretti, M.C.; Crosta, F.; Vitali, A.; Guerrieri, M.; Frontini, A.; Cannon, B.; Nedergaard, J.; Cinti, S. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J. 2009, 23, 3113–3120. [Google Scholar] [CrossRef]
- Cannon, B.; Nedergaard, J. Brown Adipose Tissue: Function and Physiological Significance. Physiol. Rev. 2004, 84, 277–359. [Google Scholar] [CrossRef]
- Kajimura, S.; Saito, M. A New Era in Brown Adipose Tissue Biology: Molecular Control of Brown Fat Development and Energy Homeostasis. Annu. Rev. Physiol. 2014, 76, 225–249. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nedergaard, J.; Cannon, B. The Changed Metabolic World with Human Brown Adipose Tissue: Therapeutic Visions. Cell Metab. 2010, 11, 268–272. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, J.; Cohen, P.; Spiegelman, B.M. Adaptive thermogenesis in adipocytes: Is beige the new brown? Genes Dev. 2013, 27, 234–250. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, Z.; Puigserver, P.; Andersson, U.; Zhang, C.; Adelmant, G.; Mootha, V.; Troy, A.; Cinti, S.; Lowell, B.; Scarpulla, R.C. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 1999, 98, 115–124. [Google Scholar] [CrossRef]
- Yuan, X.; Wei, G.; You, Y.; Huang, Y.; Lee, H.J.; Dong, M.; Lin, J.; Hu, T.; Zhang, H.; Zhang, C. Rutin ameliorates obesity through brown fat activation. Faseb J. 2017, 31, 333–345. [Google Scholar] [CrossRef]
- Walker, A.W.; Parkhill, J. Fighting Obesity with Bacteria. Science 2013, 341, 1069–1070. [Google Scholar] [CrossRef]
- Turnbaugh, P.J.; Ley, R.E.; Mahowald, M.A.; Magrini, V.; Mardis, E.R.; Gordon, J.I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006, 444, 1027–1031. [Google Scholar] [CrossRef]
- Qiao, Y.; Sun, J.; Ding, Y.; Le, G.; Shi, Y. Alterations of the gut microbiota in high-fat diet mice is strongly linked to oxidative stress. Appl. Microbiol. Biotechnol. 2013, 97, 1689–1697. [Google Scholar] [CrossRef]
- Gorissen, L.; Raes, K.; Weckx, S.; Dannenberger, D.; Leroy, F.; Vuyst, L.D.; Smet, S.D. Production of conjugated linoleic acid and conjugated linolenic acid isomers by Bifidobacterium species. Appl. Microbiol. Biotechnol. 2010, 87, 2257–2266. [Google Scholar] [CrossRef]
- Million, M.; Maraninchi, M.; Henry, M.; Armougom, F.; Richet, H.; Carrieri, P.; Valero, R.; Raccah, D.; Vialettes, B.; Raoult, D. Obesity-associated gut microbiota is enriched in Lactobacillus reuteri and depleted in Bifidobacterium animalis and Methanobrevibacter smithii. Int. J. Obes. 2012, 36, 817–825. [Google Scholar] [CrossRef]
- Frankenfeld, C.L.; Atkinson, C.; Wahala, K.; Lampe, J.W. Obesity prevalence in relation to gut microbial environments capable of producing equol or O-desmethylangolensin from the isoflavone daidzein. Eur. J. Clin. Nutr. 2014, 68, 526–530. [Google Scholar] [CrossRef] [PubMed]
- Lee, E.-H.; Son, W.-C.; Lee, S.-E.; Kim, B.-H. Anti-obesity effects of poly-gamma-glutamic acid with or without isoflavones on high-fat diet induced obese mice. Biosci. Biotechnol. Biochem. 2013, 77, 1694–1702. [Google Scholar] [CrossRef] [PubMed]
- Wang, S.; Moustaid-Moussa, N.; Chen, L.; Mo, H.; Shastri, A.; Su, R.; Bapat, P.; Kwun, I.; Shen, C.-L. Novel insights of dietary polyphenols and obesity. J. Nutr. Biochem. 2014, 25, 1–18. [Google Scholar] [CrossRef] [PubMed]
- Hursel, R.; Westerterp-Plantenga, M.S. Catechin- and caffeine-rich teas for control of body weight in humans. Am. J. Clin. Nutr. 2013, 98, 1682S–1693S. [Google Scholar] [CrossRef] [PubMed] [Green Version]
OTU that Changed by the Water Extract of Caulis Spatholobi | Increase/Decrease Of The HFD+CSH Group Compared with the HFD Group | p-Value | |
---|---|---|---|
Level of family | Clostridiaceae | ↑ | 0.036487607 |
Lachnospiraceae | ↓ | <0.0001 | |
Ruminococcaceae | ↑ | 0.033080246 | |
Erysipelotrichaceae | ↑ | 0.047428491 | |
Level of genus | Facklamia | ↓ | 0.0142127 |
Enterococcus | ↓ | 0.0035 | |
Lactobacillus | ↑ | 0.002309373 | |
Candidatus Arthromitus | ↑ | 0.028112884 | |
Ruminococcus | ↑ | 0.036487607 | |
Bacteroides | ↓ | <0.0001 | |
Prevotella | ↓ | <0.0001 | |
Adlercreutzia | ↑ | 0.010054934 | |
Dehalobacterium | ↓ | 0.011452914 | |
Lactococcus | ↓ | <0.0001 | |
Oscillospira | ↑ | 0.005455646 | |
Leuconostoc | ↓ | <0.0001 | |
Anaerotruncus | ↑ | 0.0159 | |
Roseburia | ↓ | 0.029076172 | |
Parabacteroides | ↑ | 0.0018 |
© 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
Zhang, C.; Liu, J.; He, X.; Sheng, Y.; Yang, C.; Li, H.; Xu, J.; Xu, W.; Huang, K. Caulis Spatholobi Ameliorates Obesity through Activating Brown Adipose Tissue and Modulating the Composition of Gut Microbiota. Int. J. Mol. Sci. 2019, 20, 5150. https://doi.org/10.3390/ijms20205150
Zhang C, Liu J, He X, Sheng Y, Yang C, Li H, Xu J, Xu W, Huang K. Caulis Spatholobi Ameliorates Obesity through Activating Brown Adipose Tissue and Modulating the Composition of Gut Microbiota. International Journal of Molecular Sciences. 2019; 20(20):5150. https://doi.org/10.3390/ijms20205150
Chicago/Turabian StyleZhang, Chuanhai, Junyu Liu, Xiaoyun He, Yao Sheng, Cui Yang, Haoyu Li, Jia Xu, Wentao Xu, and Kunlun Huang. 2019. "Caulis Spatholobi Ameliorates Obesity through Activating Brown Adipose Tissue and Modulating the Composition of Gut Microbiota" International Journal of Molecular Sciences 20, no. 20: 5150. https://doi.org/10.3390/ijms20205150