Subtherapeutic dose of pioglitazone reduces expression of inflammatory adipokines in db/db mice.
Agonists of the thiazolidinedione class of peroxisome proliferator-activated receptor-gamma exhibit both insulin-sensitizing and anti-inflammatory effects. We hypothesized that pioglitazone might be able to exert its anti-inflammatory properties at a lower dose than that required for its insulin-sensitizing effect. In order to investigate this hypothesis, we evaluated the effects of pioglitazone on inflammatory as well as metabolic biomarkers in serum and white adipose tissue (WAT) at 2 different doses. Female db/db mice were treated orally with therapeutic (30 mg/kg) and subtherapeutic (3 mg/kg) doses of pioglitazone for 14 days followed by an oral glucose tolerance test. Other parameters measured were inflammatory markers such as tumor necrosis factor (TNF)-alpha, interleukin-6 (IL-6) and metabolic biomarkers in serum (insulin, glucose and adiponectin). Moreover, adiponectin, fatty acid-binding protein (aP2) and lipoprotein lipase (LPL) mRNA expression in WAT were determined by real-time PCR. A subtherapeutic dose of pioglitazone significantly suppresses the expression of TNF-alpha and IL-6 mRNA in WAT, but does not alter the serum glucose, insulin and WAT expression of adiponectin, adipocyte aP2 and LPL. A therapeutic dose of pioglitazone improves insulin sensitivity, enhances LPL, aP2 and adiponectin expression, and also suppresses TNF-alpha and IL-6 expression. In conclusion, the current study indicates that the anti-inflammatory effect of pioglitazone is produced at a subtherapeutic dose, which is considerably lower than the dose needed to produce any desired metabolic effects. Anti-inflammatory effects of pioglitazone may precede its insulin-sensitizing effects in db/db mice.
Mohapatra
Jogeswar
J
Zydus Research Centre, Ahmedabad, India.
Sharma
Manoranjan
M
Singh
Satinder
S
Chatterjee
Abhijit
A
Swain
Prabodha
P
Balaraman
R
R
Patel
Pankaj R
PR
Jain
Mukul R
MR
D054392:Adipokines / Q000097:blood / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008071:Lipoprotein Lipase / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*
D054392:Adipokines; D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D050556:Fatty Acid-Binding Proteins; D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D007328:Insulin; D045162:Thiazolidinediones; D008071:Lipoprotein Lipase; D000077205:Pioglitazone