Title | Association of scavenger receptors in adipose tissue with insulin resistance in nondiabetic humans. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Rasouli N, Yao-Borengasser A, Varma V, Spencer HJ, McGehee RE, Peterson CA, Mehta JL, Kern PA |
Journal | Arterioscler Thromb Vasc Biol |
Volume | 29 |
Issue | 9 |
Pagination | 1328-35 |
Date Published | 2009 Sep |
ISSN | 1524-4636 |
Keywords | Adipocytes, Adiponectin, Adult, Aged, CD36 Antigens, Cell Line, Coculture Techniques, Down-Regulation, Female, Humans, Hypoglycemic Agents, Insulin Resistance, Macrophages, Male, Metformin, Middle Aged, Obesity, Pioglitazone, Receptors, Scavenger, RNA, Messenger, Scavenger Receptors, Class A, Scavenger Receptors, Class E, Subcutaneous Fat, Thiazolidinediones, Treatment Outcome, Young Adult |
Abstract | 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. METHODS AND 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. |
DOI | 10.1161/ATVBAHA.109.186957 |
Alternate Journal | Arterioscler. Thromb. Vasc. Biol. |
PubMed ID | 19667111 |
PubMed Central ID | PMC2755066 |
Grant List | R01 DK039176 / DK / NIDDK NIH HHS / United States R37 DK039176 / DK / NIDDK NIH HHS / United States R01 DK071349 / DK / NIDDK NIH HHS / United States DK 71349 / DK / NIDDK NIH HHS / United States DK 39176 / DK / NIDDK NIH HHS / United States DK 71277 / DK / NIDDK NIH HHS / United States R37 DK039176-21 / DK / NIDDK NIH HHS / United States R01 DK071277 / DK / NIDDK NIH HHS / United States R01 DK071277-04 / DK / NIDDK NIH HHS / United States R01 DK071349-04 / DK / NIDDK NIH HHS / United States UL1 TR001998 / TR / NCATS NIH HHS / United States M01 RR014288 / RR / NCRR NIH HHS / United States M01RR14288 / RR / NCRR NIH HHS / United States P20 RR021954 / RR / NCRR NIH HHS / United States P20 RR021954-02 / RR / NCRR NIH HHS / United States |