Association of scavenger receptors in adipose tissue with insulin resistance in nondiabetic humans.
OBJECTIVE
Scavenger receptors play crucial roles in the pathogenesis of atherosclerosis, but their role in insulin resistance has not been explored. We hypothesized that scavenger receptors are present in human adipose tissue resident macrophages, and their gene expression is regulated by adiponectin and thaizolidinediones.


RESULTS
The gene expression of scavenger receptors including scavenger receptor-A (SRA), CD36, and lectin-like oxidized LDL receptor-1 (LOX-1) were studied in subcutaneous adipose tissue of nondiabetic subjects and in vitro. Adipose tissue SRA expression was independently associated with insulin resistance. Pioglitazone downregulated SRA gene expression in adipose tissue of subjects with impaired glucose tolerance and decreased LOX-1 mRNA in vitro. Macrophage LOX-1 expression was decreased when macrophages were cocultured with adipocytes or when exposed to adipocyte conditioned medium. Adding adiponectin neutralizing antibody resulted in a 2-fold increase in LOX-1 gene expression demonstrating that adiponectin regulates LOX-1 expression.


CONCLUSIONS
Adipose tissue scavenger receptors are strongly associated with insulin resistance. Pioglitazone and adiponectin regulate gene expression of SRA and LOX-1, and this may have clinical implications in arresting the untoward sequalae of insulin resistance and diabetes, including accelerated atherosclerosis.
Rasouli
Neda
N
Central Arkansas Veterans Healthcare System, 111J, 4300 West 7th Street, Little Rock, AR 72205, USA. Rasoulineda@uams.edu
Yao-Borengasser
Aiwei
A
Varma
Vijayalakshmi
V
Spencer
Horace J
HJ
McGehee
Robert E
RE
Peterson
Charlotte A
CA
Mehta
Jawahar L
JL
Kern
Philip A
PA
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism; D000328:Adult; D000368:Aged; D018955:CD36 Antigens / Q000187:drug effects; D002460:Cell Line; D018920:Coculture Techniques; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000378:metabolism; D051116:Receptors, Scavenger / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000187:drug effects; D051127:Scavenger Receptors, Class E / Q000187:drug effects; D050151:Subcutaneous Fat / Q000187:drug effects* / Q000378:metabolism; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
C499918:ADIPOQ protein, human; D052242:Adiponectin; D018955:CD36 Antigens; D007004:Hypoglycemic Agents; C495137:OLR1 protein, human; D012333:RNA, Messenger; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051127:Scavenger Receptors, Class E; D045162:Thiazolidinediones; D008687:Metformin; D000077205:Pioglitazone