title: Astragaloside IV improves lipid metabolism in obese mice by alleviation of leptin resistance and regulation of thermogenic network.
abstract: Obesity is a worldwide threat to public health in modern society, which may result from leptin resistance and disorder of thermogenesis. The present study investigated whether astragaloside IV (ASI) could prevent obesity in high-fat diet (HFD)-fed and db/db mice. In HFD-fed mice, ASI prevented body weight gain, lowered serum triglyceride and total cholesterol levels, mitigated liver lipid accumulation, reduced fat tissues and decreased the enlargement of adipose cells. In metabolic chambers, ASI lessened appetite of the mice, decreased their respiratory exchange ratio and elevated VCO2 and VO2 without altering circadian motor activity. Moreover, ASI modulated thermogenesis associated gene expressions in liver and brawn fat tissues, as well as leptin resistance evidenced by altered expressions of leptin, leptin receptor (ObR) or appetite associated genes. In SH-SY5Y cells, ASI enhanced leptin signaling transduction. However, in db/db mice, ASI did not change body weight gain and appetite associated genes. But it decreased serum triglyceride and total cholesterol levels as well as liver triglyceride. Meanwhile, it significantly modulated gene expressions of PPARα, PGC1-α, UCP2, ACC, SCD1, LPL, AP2, CD36 and SREBP-1c. Collectively, our study suggested that ASI could efficiently improve lipid metabolism in obese mice probably through enhancing leptin sensitivity and modulating thermogenic network.
authors.affiliation: Shanghai Key Laboratory of Complex Prescription, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: Shanghai Key Laboratory of Complex Prescription, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Shanghai Key Laboratory of Complex Prescription, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
authors.forename: Hai-Lian
authors.initials: HL
authors.lastname: Shi
authors.affiliation: Shanghai Key Laboratory of Complex Prescription, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
authors.forename: Li-Yue
authors.initials: LY
authors.lastname: Qin
authors.affiliation: Shanghai Key Laboratory of Complex Prescription, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Huang
authors.affiliation: Shanghai Key Laboratory of Complex Prescription, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
authors.forename: Yun-Yi
authors.initials: YY
authors.lastname: Lan
authors.affiliation: Shanghai Key Laboratory of Complex Prescription, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Complex Prescription, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
authors.forename: Zhi-Bi
authors.initials: ZB
authors.lastname: Hu
authors.affiliation: Shanghai Key Laboratory of Complex Prescription, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Wu
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D059305:Diet, High-Fat / Q000009:adverse effects; D015870:Gene Expression / Q000187:drug effects; D020738:Leptin / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism*; D054411:Receptors, Leptin / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D022722:Thermogenesis / Q000187:drug effects*; D014280:Triglycerides / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D012503:Saponins; D014280:Triglycerides; D014315:Triterpenes; C052064:astragaloside A