ApoA-I Milano stimulates lipolysis in adipose cells independently of cAMP/PKA activation.

Summary, in English

ApoA-I, the main protein component of high-density lipoprotein (HDL), is suggested to be involved in metabolic homeostasis. We examined the effects of Milano, a naturally occurring ApoA-I variant, about which little mechanistic information is available. Remarkably, high fat-fed mice treated with Milano displayed a rapid weight loss greater than ApoA-I WT treated mice, and a significantly reduced adipose tissue mass, without an inflammatory response. Further, lipolysis in adipose cells isolated from mice treated with either WT or Milano was increased. In primary rat adipose cells, Milano stimulated cholesterol efflux and increased glycerol release, independently of β-adrenergic stimulation and phosphorylation of hormone sensitive lipase (Ser563) and perilipin (Ser522). Stimulation with Milano had a significantly greater effect on glycerol release compared with WT but similar effect on cholesterol efflux. Pharmacological inhibition or siRNA silencing of ABCA-1 did not diminish Milano-stimulated lipolysis, although binding to the cell surface was decreased, as analyzed by fluorescence microscopy. Interestingly, methyl-β-cyclodextrin, a well-described cholesterol acceptor, dose-dependently stimulated lipolysis. Together, these results suggest that decreased fat mass and increased lipolysis following Milano treatment in vivo is partly explained by a novel mechanism at the adipose cell level comprising stimulation of lipolysis independently of the canonical cAMP/PKA signaling pathway.

• Author: Maria Lindahl; Jitka Petrlova; Jonathan Dalla-Riva; Sebastian Wasserstrom; Catarina Rippe; Joan Domingo-Espin; Dorota Kotowska; Ewa Krupinska; Christine Berggreen; Helena Jones; Karl Swärd; Jens Lagerstedt; Olga Göransson; Karin Stenkula
• Department/s: Glucose Transport and Protein Trafficking; Dermatology and Venereology (Lund); Medical Protein Science; Cellular Biomechanics; Molecular Cell Biology; Protein Phosphorylation; Molecular Endocrinology; EXODIAB: Excellence of Diabetes Research in Sweden
• Publishing year: 2015
• Language: English
• Pages: 2248-2259
• Publication/Series: Journal of Lipid Research
• Volume: 56
• Issue: 12
• Links: http://www.ncbi.nlm.nih.gov/pubmed/26504176?dopt=Abstract; http://dx.doi.org/10.1194/jlr.M054767
• Document type: Journal article
• Publisher: American Society for Biochemistry and Molecular Biology
• Topic: Cell and Molecular Biology
• Status: Published
• Research group: Glucose Transport and Protein Trafficking; Medical Protein Science; Cellular Biomechanics; Protein Phosphorylation; Molecular Endocrinology
• ISBN/ISSN/Other: ISSN: 1539-7262