title: Reactive oxygen species facilitate translocation of hormone sensitive lipase to the lipid droplet during lipolysis in human differentiated adipocytes.
abstract: In obesity, there is an increase in reactive oxygen species (ROS) within adipose tissue caused by increases in inflammation and overnutrition. Hormone sensitive lipase (HSL) is part of the canonical lipolytic pathway and critical for complete lipolysis. This study hypothesizes that ROS is a signal that integrates regulation of lipolysis by targeting HSL. Experiments were performed with human differentiated adipocytes from the subcutaneous depot. Antioxidants were employed as a tool to decrease ROS, and it was found that scavenging ROS with diphenyliodonium, N-acetyl cysteine, or resveratrol decreased lipolysis in adipocytes. HSL phosphorylation of a key serine residue, Ser552, as well as translocation of this enzyme from the cytosol to the lipid droplet upon lipolytic stimulation were both abrogated by scavenging ROS. The phosphorylation status of other serine residues on HSL were not affected. These findings are significant because they document that ROS contributes to the physiological regulation of lipolysis via an effect on translocation. Such regulation could be useful in developing new obesity therapies.
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America. krawczyk@bu.edu
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Krawczyk
authors.forename: Jorge F
authors.initials: JF
authors.lastname: Haller
authors.forename: Tom
authors.initials: T
authors.lastname: Ferrante
authors.forename: Raphael A
authors.initials: RA
authors.lastname: Zoeller
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Corkey
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000975:Antioxidants / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D005576:Colforsin / Q000009:adverse effects; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008066:Lipolysis / Q000187:drug effects; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D009861:Onium Compounds / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D021381:Protein Transport / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077185:Resveratrol; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D002787:Sterol Esterase / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D008055:Lipids; D009861:Onium Compounds; D017382:Reactive Oxygen Species; D013267:Stilbenes; C031291:diphenyliodonium; D005576:Colforsin; D012694:Serine; D002787:Sterol Esterase; D000077185:Resveratrol; D000111:Acetylcysteine