title: Andrographolide prevents high-fat diet-induced obesity in C57BL/6 mice by suppressing the sterol regulatory element-binding protein pathway.
abstract: Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acids, and triglycerides. We investigated the effect of the specific SREBP suppressor andrographolide, a natural compound isolated from Andrographis paniculata, on the regulation of SREBP signaling by use of Western blot, reporter gene assay, and quantitative real-time polymerase chain reaction analysis. In addition, the antiobesity effects of andrographolide were evaluated in C57BL/6 mice with high-fat diet (HFD)-induced obesity. Our results showed that andrographolide downregulated the expressions of SREBPs target genes and decreased cellular lipid accumulation in vitro. Further, andrographolide (100 mg/kg per day) attenuated HFD-induced body weight gain and fat accumulation in liver or adipose tissues, and improved serum lipid levels and insulin or glucose sensitivity in HFD-induced obese mice. Andrographolide effectively suppressed the respiratory quotient, energy expenditure, and oxygen consumption, which may have contributed to the decreased body-weight gain of the obese mice fed with a HFD. Consistently, andrographolide regulated SREBP target genes and metabolism-associated genes in liver or brown adipose tissue, which may have directly contributed to the lower lipid levels and enhanced insulin sensitivity. Taken together, our results indicated that andrographolide ameliorated lipid metabolism and improved glucose use in mice with HFD-induced obesity. Andrographolide has potential as a leading compound in the prevention or treatment of obesity and insulin resistance.
authors.affiliation: Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China (B.S., X.X.); Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, California (W.H.); and Department of Pharmacognosy, China Pharmaceutical University, Nanjing, People's Republic of China (J.L.).
authors.forename: Lili
authors.initials: L
authors.lastname: Ding
authors.affiliation: Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China (B.S., X.X.); Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, California (W.H.); and Department of Pharmacognosy, China Pharmaceutical University, Nanjing, People's Republic of China (J.L.).
authors.forename: Jinmei
authors.initials: J
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China (B.S., X.X.); Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, California (W.H.); and Department of Pharmacognosy, China Pharmaceutical University, Nanjing, People's Republic of China (J.L.).
authors.forename: Baoliang
authors.initials: B
authors.lastname: Song
authors.affiliation: Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China (B.S., X.X.); Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, California (W.H.); and Department of Pharmacognosy, China Pharmaceutical University, Nanjing, People's Republic of China (J.L.).
authors.forename: Xu
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China (B.S., X.X.); Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, California (W.H.); and Department of Pharmacognosy, China Pharmaceutical University, Nanjing, People's Republic of China (J.L.).
authors.forename: Wendong
authors.initials: W
authors.lastname: Huang
authors.affiliation: Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China (B.S., X.X.); Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, California (W.H.); and Department of Pharmacognosy, China Pharmaceutical University, Nanjing, People's Republic of China (J.L.).
authors.forename: Binfeng
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China (B.S., X.X.); Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, California (W.H.); and Department of Pharmacognosy, China Pharmaceutical University, Nanjing, People's Republic of China (J.L.).
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Tang
authors.affiliation: Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China (B.S., X.X.); Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, California (W.H.); and Department of Pharmacognosy, China Pharmaceutical University, Nanjing, People's Republic of China (J.L.).
authors.forename: Meng
authors.initials: M
authors.lastname: Qi
authors.affiliation: Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China (B.S., X.X.); Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, California (W.H.); and Department of Pharmacognosy, China Pharmaceutical University, Nanjing, People's Republic of China (J.L.).
authors.forename: Qiming
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China (B.S., X.X.); Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, California (W.H.); and Department of Pharmacognosy, China Pharmaceutical University, Nanjing, People's Republic of China (J.L.).
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China (B.S., X.X.); Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, California (W.H.); and Department of Pharmacognosy, China Pharmaceutical University, Nanjing, People's Republic of China (J.L.) yangli7951@hotmail.com wangzht@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, People's Republic of China (L.D., J.L., B.Z., X.T., M.Q., Qim.Y., Qia.Y., L.Y., Z.W.); State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China (B.S., X.X.); Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center, Duarte, California (W.H.); and Department of Pharmacognosy, China Pharmaceutical University, Nanjing, People's Republic of China (J.L.) yangli7951@hotmail.com wangzht@hotmail.com.
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Wang
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D059305:Diet, High-Fat / Q000009:adverse effects*; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D004224:Diterpenes; D007328:Insulin; D008055:Lipids; D051779:Sterol Regulatory Element Binding Proteins; C030419:andrographolide; D005947:Glucose