title: Effect of endoplasmic reticulum stress on inflammation and adiponectin regulation in human adipocytes.
abstract: The endoplasmic reticulum (ER) of adipocytes plays a major role in the assembly and secretion of adipokines. The levels of serum adiponectin, secreted by adipocytes, are decreased in insulin resistance, diabetes, and obesity. The role of ER stress in downregulating adiponectin levels has been demonstrated in mouse models of obesity. Studies examining human adipose tissue have indicated that there is an increase in the ER stress transcript HSPA5 with increased body mass index (BMI). However, it is not established whether ER stress results in changes in adiponectin levels or multimerization in human adipocytes. We examined whether the induction of ER stress using tunicamycin, thapsigargin, or palmitate alters the messenger RNA (mRNA) and protein expression of adiponectin and the mRNA expression of chaperones ERP44 and ERO1 in adult-derived human adipocyte stem (ADHAS) cells. ER stress was measured using key indicators of ER stress-HSPA5, ERN1, CHOP, and GADD34, as well as changes in eIF2α phosphorylation. Because ER stress is suggested to be the proximal cause of inflammation in adipocytes, we further examined the change in inflammatory status by quantitating the change in Iκβ-α protein following the induction of ER stress. Our studies indicate that: (1) ER stress markers were increased to a higher degree using tunicamycin or thapsigargin compared to palmitate; (2) ER stress significantly decreased adiponectin mRNA in response to tunicamycin and thapsigargin, but palmitate did not decrease adiponectin mRNA levels. In all three instances, the induction of ER stress was accompanied by a decrease in adiponectin protein as well as adiponectin multimerization. All three inducers of ER stress increased tumor necrosis factor-α (TNF-α) mRNA and decreased Iκβ-α protein in adipocytes. The data suggest that ER stress modifies adiponectin secretion and induces inflammation in ADHAS cells.
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Ashis K
authors.initials: AK
authors.lastname: Mondal
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Das
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Varma
authors.forename: Greg T
authors.initials: GT
authors.lastname: Nolen
authors.forename: Robert E
authors.initials: RE
authors.lastname: McGehee
authors.forename: Steven C
authors.initials: SC
authors.lastname: Elbein
authors.forename: Jeanne Y
authors.initials: JY
authors.lastname: Wei
authors.forename: Gouri
authors.initials: G
authors.lastname: Ranganathan
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D052242:Adiponectin / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D015992:Body Mass Index; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism; D010766:Phosphorylation; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D019284:Thapsigargin / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D052242:Adiponectin; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; D012333:RNA, Messenger; D014415:Tunicamycin; D019308:Palmitic Acid; D012313:RNA; D019284:Thapsigargin