Audit report on O’Brien County, Iowa for the year ended June 30, 2010

Audit report on O’Brien County, Iowa for the year ended June 30, 2010

Audit report on Page County, Iowa for the year ended June 30, 2010

Audit report on Page County, Iowa for the year ended June 30, 2010

Audit report on Story County, Iowa for the year ended June 30, 2010

Audit report on Story County, Iowa for the year ended June 30, 2010

Audit report on the Pocahontas County Solid Waste Commission for the year ended June 30, 2010

Audit report on the Pocahontas County Solid Waste Commission for the year ended June 30, 2010

Audit report on Warren County, Iowa for the year ended June 30, 2010

Audit report on Warren County, Iowa for the year ended June 30, 2010

Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) but not PPARalpha serves as a plasma free fatty acid sensor in liver.

Peroxisome proliferator-activated receptor alpha (PPARalpha) is an important transcription factor in liver that can be activated physiologically by fasting or pharmacologically by using high-affinity synthetic agonists. Here we initially set out to elucidate the similarities in gene induction between Wy14643 and fasting. Numerous genes were commonly regulated in liver between the two treatments, including many classical PPARalpha target genes, such as Aldh3a2 and Cpt2. Remarkably, several genes induced by Wy14643 were upregulated by fasting independently of PPARalpha, including Lpin2 and St3gal5, suggesting involvement of another transcription factor. Using chromatin immunoprecipitation, Lpin2 and St3gal5 were shown to be direct targets of PPARbeta/delta during fasting, whereas Aldh3a2 and Cpt2 were exclusive targets of PPARalpha. Binding of PPARbeta/delta to the Lpin2 and St3gal5 genes followed the plasma free fatty acid (FFA) concentration, consistent with activation of PPARbeta/delta by plasma FFAs. Subsequent experiments using transgenic and knockout mice for Angptl4, a potent stimulant of adipose tissue lipolysis, confirmed the stimulatory effect of plasma FFAs on Lpin2 and St3gal5 expression levels via PPARbeta/delta. In contrast, the data did not support activation of PPARalpha by plasma FFAs. The results identify Lpin2 and St3gal5 as novel PPARbeta/delta target genes and show that upregulation of gene expression by PPARbeta/delta is sensitive to plasma FFA levels. In contrast, this is not the case for PPARalpha, revealing a novel mechanism for functional differentiation between PPARs.

Audit report on the Shelby County Area Solid Waste Agency for the year ended June 30, 2010

Audit report on the Shelby County Area Solid Waste Agency for the year ended June 30, 2010

Audit report on the Fremont County Landfill Commission for the year ended June 30, 2010

Audit report on the Fremont County Landfill Commission for the year ended June 30, 2010

Audit report on Audubon County, Iowa for the year ended June 30, 2010

Audit report on Audubon County, Iowa for the year ended June 30, 2010

County Medical Examiners, February 11, 2011

A directory of County Medical Examiners from the Iowa Office of the State Medical Examiner.

Audit report on the Crawford County Area Solid Waste Agency Commission for the year ended June 30, 2010

Audit report on the Crawford County Area Solid Waste Agency Commission for the year ended June 30, 2010

Audit report on the Page County Landfill Association for the year ended June 30, 2010

Audit report on the Page County Landfill Association for the year ended June 30, 2010

Activation of peroxisome proliferator-activated receptor beta/delta inhibits lipopolysaccharide-induced cytokine production in adipocytes by lowering nuclear factor-kappaB activity via extracellular signal-related kinase 1/2.

OBJECTIVE: Chronic activation of the nuclear factor-kappaB (NF-kappaB) in white adipose tissue leads to increased production of pro-inflammatory cytokines, which are involved in the development of insulin resistance. It is presently unknown whether peroxisome proliferator-activated receptor (PPAR) beta/delta activation prevents inflammation in adipocytes. RESEARCH DESIGN AND METHODS AND RESULTS: First, we examined whether the PPARbeta/delta agonist GW501516 prevents lipopolysaccharide (LPS)-induced cytokine production in differentiated 3T3-L1 adipocytes. Treatment with GW501516 blocked LPS-induced IL-6 expression and secretion by adipocytes and the subsequent activation of the signal transducer and activator of transcription 3 (STAT3)-Suppressor of cytokine signaling 3 (SOCS3) pathway. This effect was associated with the capacity of GW501516 to impede LPS-induced NF-kappaB activation. Second, in in vivo studies, white adipose tissue from Zucker diabetic fatty (ZDF) rats, compared with that of lean rats, showed reduced PPARbeta/delta expression and PPAR DNA-binding activity, which was accompanied by enhanced IL-6 expression and NF-kappaB DNA-binding activity. Furthermore, IL-6 expression and NF-kappaB DNA-binding activity was higher in white adipose tissue from PPARbeta/delta-null mice than in wild-type mice. Because mitogen-activated protein kinase-extracellular signal-related kinase (ERK)1/2 (MEK1/2) is involved in LPS-induced NF-kappaB activation in adipocytes, we explored whether PPARbeta/delta prevented NF-kappaB activation by inhibiting this pathway. Interestingly, GW501516 prevented ERK1/2 phosphorylation by LPS. Furthermore, white adipose tissue from animal showing constitutively increased NF-kappaB activity, such as ZDF rats and PPARbeta/delta-null mice, also showed enhanced phospho-ERK1/2 levels. CONCLUSIONS: These findings indicate that activation of PPARbeta/delta inhibits enhanced cytokine production in adipocytes by preventing NF-kappaB activation via ERK1/2, an effect that may help prevent insulin resistance.

Audit report on Butler County, Iowa for the year ended June 30, 2010

Audit report on Butler County, Iowa for the year ended June 30, 2010

Audit report on Appanoose County, Iowa for the year ended June 30, 2010

Audit report on Appanoose County, Iowa for the year ended June 30, 2010