Effects of lobeglitazone, a novel thiazolidinedione, on adipose tissue remodeling and brown and beige adipose tissue development in db/db mice.

BACKGROUND/OBJECTIVES: We investigated the effect of long-term treatment with lobeglitazone, a novel thiazolidinedione-based activator of peroxisome proliferator-activated receptor gamma, on adipose tissue (AT), focusing on its effects on insulin resistance in obese db/db mice. METHODS: Seven-week-old male db/db mice were assigned to either a vehicle-treated (n=8) or lobeglitazone-treated (n=8) group. Lobeglitazone (1 mg kg-1 daily) was injected intraperitoneally for 20 weeks. RESULTS: Lobeglitazone treatment for 20 weeks resulted in a remarkably improved glycemic index, including significantly decreased glucose levels, enhanced insulin sensitivity and preserved pancreatic beta cells. Both whole body and subcutaneous AT weight increased in the lobeglitazone-treated group. However, lobeglitazone induced an increase in the number of small adipocyte in both epididymal and subcutaneous AT, with a significant weight decrease in the epididymal AT of db/db mice. Using flow cytometry, the CD11c-positive M1 macrophages and CD206-positive M2 macrophages in the epididymal AT were observed to exhibit a decreased M1-to-M2 ratio in lobeglitazone-treated db/db mice. Furthermore, in the lobeglitazone-treated group, interscapular brown AT was clearly visualized by 18F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT) and its mass was significantly greater than that of the vehicle-treated group. In the lobeglitazone-treated group, beige-specific gene expression and the number of mitochondria in white AT were upregulated. Lobeglitazone, with upregulating interferon regulatory factor-4 (a key transcriptional regulator of thermogenesis), promoted the development of brown adipocytes and the differentiation of white adipocytes into beige adipocytes. CONCLUSIONS: Long-term lobeglitazone treatment has a beneficial role in remodeling and ameliorating inflammation in white AT and in glycemic control, in relation to insulin sensitivity in obese db/db mice. Moreover, lobeglitazone induced the differentiation of brown and beige adipocytes. Collectively, our data suggest that lobeglitazone treatment provides promising effects on white and brown AT as well as great improvement in glycemic control, as a potent insulin sensitizer.

Prevalence and characteristics of intimin-producing Escherichia coli strains isolated from healthy chickens in Korea.

Virulent Escherichia coli strains have commonly been associated with diarrheal illness in humans and animals. Typical enteropathogenic Escherichia coli (EPEC) with intimin gene (eaeA) and E. coli adherence factor plasmid, or atypical EPEC with only eaeA have been implicated in human cases. In the present study, we investigated the prevalence of virulence-associated genes including eaeA in the E. coli strains isolated from cloacal specimens of 184 chicken flocks in 7 provinces in Korea between 2009 and 2010. When 7 virulence genes (VT1, VT2, LT, and ST for enterotoxigenic E. coli; eaeA and bfpA for enteropathogenic E. coli; and aggR for enteroaggregative E. coli) were screened by multiplex PCR, a total of 30 E. coli strains carrying only the eaeA gene were detected from 184 flocks that were identified as atypical enteropathogenic Escherichia coli (aEPEC). The aEPEC strains were analyzed by eae subtyping, phylogenetic grouping PCR, and serotyping. Twelve (40%) of 30 aEPEC strains possessed an eae-ß subtype, followed by θ (30%), ε (16.7%), and ß1 (13.3%). Eight (26.7%) of 30 aEPEC strains were designated into the phylogenetic group A. Two (6.7%) and 3 (10%) aEPEC strains were classified into the phylogenetic group B2 and D, respectively. A total of 15 (50%) aEPEC strains were serotyped to groups O24, O25, O26, O71, O80, O103, and O157, and the remaining strains were nontypeable. In analyzing the genetic diversity among the 30 aEPEC isolates by the pulsed-field gel electrophoresis method with XbaI-digestion, the pulsed-field gel electrophoresis profiling produced 20 different patterns, but isolates within the same group did not show clear geographic or breed relationships. Our data indicate that healthy chickens may constitute an important natural reservoir of aEPEC strains, and suggest that transmission to humans could not be excluded.

The embryo lethality of Escherichia coli isolates and its relationship to the presence of virulence-associated genes.

The aims of this study were to determine if the chicken embryo lethality assay and the presence of 9 virulence-associated genes of Escherichia coli were correlated and to discover which virulence genes contributed most to embryo lethality. We examined 58 E. coli strains isolated from visceral organs of chickens with colibacillosis for the presence of 9 virulence genes (fimC, tsh, fyuA, irp2, iucD, cvi/cva, iss, astA, and vat) by PCR. The gene FimC (type I fimbriae) was detected with the highest prevalence in 93.1% of the isolates, followed by iucD (67.24%), iss (58.62%), tsh (34.48%), cvi/cva (34.48%), fyuA (32.76%), astA (31.0%), irp2 (27.59%), and vat (17.24%). The embryo mortality ranged from 5 to 100%; however, most of the isolates were moderately or highly virulent. High positive correlations were observed between the presence of virulence genes and chicken embryo lethality. In addition, presence of the iucD (aerobactin) gene was the trait that best contributed to embryo mortality by using the multivariate model. These results suggest that expression frequency of these 9 virulence genes is associated with embryo mortality, and the gene that best predicted embryo mortality was iucD.

Characterization of Escherichia coli isolates from laying hens with colibacillosis on 2 commercial egg-producing farms in Korea.

The present study reports on layer chickens with colibacillosis in 2 commercial egg-producing farms (referred to as farm A and farm B, which were managed by the same owner and were about 1 km apart) in the middle region of the Korean peninsula. The 2 flocks were infected at the initiation of egg laying. They were characterized by no previous clinical signs but sudden mortality (2.7-4.0%), with severe lesions of septicemia and fibrinous polyserositis. Escherichia coli was isolated from the lesions of the infected birds. Serotyping tests identified isolates that belonged to somatic groups O1 (12/17), O46 (2/17), O78 (1/17), and O84 (1/17) or that were unidentified (1/17). Thirteen of 17 E. coli isolates (76.4%) obtained from 11 birds in the 2 flocks showed similar pulsed-field gel electrophoresis patterns that were arbitrarily designated as pattern A. The isolates had high frequencies of putative virulence genes including 100% [fimC (type 1 fimbriae), iucD (aerobactin synthesis), and iss (increased serum survival)], 94.1% [cva/cvi (structural genes of colicin V operon) and vat (vacuolating autotransporter toxin)], 88.2% [irp2, iron-repressible protein (yersinia bactin) synthesis, and fyuA, ferric yersinia uptake], and 82.3% [tsh (temperature-sensitive hemagglutinin)]; astA (encoding a heat-stable cytotoxin associated with enteroaggregative E. coli) was not associated with the enteric disorder. These data suggest that all chickens with colibacillosis on farms A and B were likely infected by E. coli strains that are highly pathogenic in avian species.