title: Curcumin inhibits lipolysis via suppression of ER stress in adipose tissue and prevents hepatic insulin resistance.
abstract: Curcumin is natural polyphenol with beneficial effects on lipid and glucose metabolism and this study aimed to investigate the effects of curcumin on lipolysis and hepatic insulin resistance. Endoplasmic reticulum (ER) stress and lipolysis signaling in adipose and FFA influx, lipid deposits, and glucose production in liver were examined. Palmitate challenge and high-fat diet feeding evoked ER stress-associated lipolysis with cAMP accumulation in adipose tissue. Curcumin treatment inhibited adipose tissue ER stress by dephosphorylation of inositol-requiring enzyme 1α and eukaryotic initiation factor 2α and reduced cAMP accumulation by preserving phosphodiesterase 3B induction. Knockdown of mitogen-activated protein kinase α1/2α with siRNAs diminished such effects of curcumin. As a result from downregulation of cAMP, curcumin blocked protein kinase (PK)A/hormone-sensitive lipase lipolysis signaling, and thereby reduced glycerol and FFA release from adipose tissue. Curcumin reduced FFA influx into the liver by blocking FFA trafficking, and then prevented diacylglycerol deposits and PKCε translocation in the liver, resultantly improving insulin action in the suppression of hepatic gluconeogenesis. Curcumin decreased adipose lipolysis by attenuating ER stress through the cAMP/PKA pathway, reduced FFA influx into the liver by blocking FFA trafficking, and thereby improved insulin sensitivity to inhibit hepatic glucose production. These findings suggested a novel pathway of curcumin to prevent lipid deposits and insulin resistance in liver by beneficial regulation of adipose function.
authors.affiliation: Jiangsu Key Laboratory of Traditional Chinese Medicine Evaluation and Translational Research, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, China State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Traditional Chinese Medicine Evaluation and Translational Research, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, China.
authors.forename: Bangling
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Traditional Chinese Medicine Evaluation and Translational Research, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.affiliation: Jiangsu Key Laboratory of Traditional Chinese Medicine Evaluation and Translational Research, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, China.
authors.forename: Baolin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Traditional Chinese Medicine Evaluation and Translational Research, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, China Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China yuanxie58@yahoo.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xie
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003474:Curcumin / Q000008:administration & dosage*; D059305:Diet, High-Fat; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008049:Lipase / Q000096:biosynthesis / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects*; D008066:Lipolysis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005230:Fatty Acids, Nonesterified; D008049:Lipase; D003474:Curcumin; D005947:Glucose
keywords: adenosine 3′,5′-cyclic monophosphate; endoplasmic reticulum; gluconeogenesis; insulin resistance; lipolysis; mitogen-activated protein kinase