title: Effect of pioglitazone on metabolic features in endotoxemia model in obese diabetic db/db mice.
abstract: BACKGROUND
  Infectious diseases are more frequent in diabetic patients, leading to increased morbidity and mortality. Endotoxemia affects glucose metabolism and lipolytic capacity. The aims of the present study were to determine whether endotoxemia exacerbates metabolic features (adipose inflammation, adipogenesis, and insulin resistance [IR]) in an animal model of diabetes (i.e. db/db mice) after acute infection and the effects of pioglitazone.
  
  
  METHODS
  Female db/db mice treated with pioglitazone (3 and 30 mg/kg, p.o.) for 14 days were challenged with lipopolysaccharide (LPS; 200 μg/kg), followed by an oral glucose tolerance test (OGTT). Quantitative real-time polymerase chain reaction (PCR) was used to evaluate the expression of genes in white adipose tissue (WAT) involved in: (i) adipogenesis (lipoprotein lipase [Lpl], fatty acid binding protein-4 [Ap2] and adiponectin [Adipoq]); (ii) insulin signaling (peroxisome proliferator-activated receptor gamma [Pparg], suppressor of cytokine signaling 3 [Socs3], solute carrier family 2 [facilitated glucose transporter], member 4 [Slc2a4]); and (iii) inflammation (tumor necrosis factor [Tnf], interleukin-6 [Il6], monocyte chemoattractant protein-1 [Ccl2], cyclo-oxygenase-2 [prostaglandin-endoperoxide synthase 2; Ptgs2]).
  
  
  RESULTS
  Experimental endotoxemia downregulated mRNA expression of Pparg, Slc2a4, Adipoq, Lpl, and Ap2, which coincided with upregulation of Il6, Tnf, Ccl2, Ptgs2, and Socs3 expression. Pioglitazone dose-dependently decreased Tnf, Il6, Ccl2, Ptgs2, and Socs3 expression in WAT, in association with upregulation of Lpl, Ap2, Slc2a4, and Adipoq expression, indicating improvement in endotoxin-induced IR.
  
  
  CONCLUSIONS
  The findings suggest that LPS challenge exacerbates IR in db/db mice by altering the expression of genes in WAT involved in adipogenesis and inflammation, which is effectively controlled by pioglitazone treatment.
authors.affiliation: Department of Pharmacology & Toxicology, Zydus Research Centre, Ahmedabad, India.
authors.forename: Manoranjan
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Department of Pharmacology & Toxicology, Zydus Research Centre, Ahmedabad, India.
authors.forename: Jogeswar
authors.initials: J
authors.lastname: Mohapatra
authors.affiliation: Department of Pharmacology & Toxicology, Zydus Research Centre, Ahmedabad, India.
authors.forename: Umar
authors.initials: U
authors.lastname: Malik
authors.affiliation: Department of Pharmacology & Toxicology, Zydus Research Centre, Ahmedabad, India.
authors.forename: Jignesh
authors.initials: J
authors.lastname: Nagar
authors.affiliation: Department of Pharmacology & Toxicology, Zydus Research Centre, Ahmedabad, India.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Chatterjee
authors.affiliation: Pharmacy Department, Sumandeep Vidyapeeth University, Vadodara, India.
authors.forename: Balaraman
authors.initials: B
authors.lastname: Ramachandran
authors.affiliation: Department of Pharmacology & Toxicology, Zydus Research Centre, Ahmedabad, India.
authors.forename: Mukul R
authors.initials: MR
authors.lastname: Jain
mesh_terms: D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism*; D019446:Endotoxemia / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D007333:Insulin Resistance / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone
keywords: adipocytokines; adipogenesis; infection; inflammation; insulin resistance; 感染; 炎症; 胰岛素抵抗; 脂肪生成; 脂肪细胞因子