West Sacramento Research Articles

Bayer outsources biologicals research

Restructuring an existing partnership, Bayer will fully outsource to Ginkgo Bioworks the R&D for its biologicals business, which is focused on using microbes to fix nitrogen in soils, fight pests, and sequester carbon. The two companies formed a joint venture called Joyn Bio in 2017, primarily to develop nitrogen-fixing microbes for cereal crops. Ginkgo will now absorb Joyn, while Bayer will market the product concepts that emerged from the partnership. As part of the deal, Ginkgo is getting Bayer’s biologicals research site in West Sacramento, California, complete with the existing team. Ginkgo’s biologicals research arm will offer services to other agricultural companies, but Bayer will remain an anchor customer. Joyn Bio CEO Michael Miille says the firm is about a third of the way to commercializing a microbial seed treatment that would fix nitrogen in soil for cereal crops like corn and wheat. He estimates that it will take roughly

Genotypic Distribution and Antimicrobial Susceptibilities of Carbapenemase-Producing Enterobacteriaceae Isolated From Rectal and Clinical Samples in Korean University Hospitals Between 2016 and 2019.

BackgroundThe emergence of carbapenemase-producing Enterobacteriaceae (CPE) represents a major clinical problem. Recently, the occurrence of CPE has increased globally, but epidemiological patterns vary across region. We report the trends in the genotypic distribution and antimicrobial susceptibility of CPE isolated from rectal and clinical samples during a four-year period.MethodsBetween January 2016 and December 2019, 1,254 nonduplicated CPE isolates were obtained from four university hospitals in Korea. Carbapenemase genotypes were determined by multiplex real-time PCR. Antimicrobial susceptibility was profiled using the Vitek 2 system (bioMérieux, Hazelwood, MO, USA) or MicroScan Walkaway-96 system (Siemens West Sacramento, CA, USA). The proportions of carbapenemase genotypes and nonsusceptibility were analyzed using Pearson’s chi-square test.ResultsAmong the 1,254 CPE isolates, 486 (38.8%), 371 (29.6%), 357 (28.5%), 8 (0.6%), 8 (0.6%), and 24 (1.9%) were Klebsiella pneumoniae carbapenemase (KPC), oxacillinase (OXA)-48-like, New Delhi metallo-β-lactamase (NDM), imipenemase (IMP), Verona integron-encoded metallo-β-lactamase (VIM), and multiple producers, respectively. The predominant species was K. pneumoniae (72.6%), followed by Escherichia coli (6.5%). More than 90% of the isolates harboring KPC, NDM, and OXA-48-like were nonsusceptible to cephalosporins, aztreonam, and carbapenems.ConclusionsThe impact of CPE is primarily due to KPC-, NDM-, and OXA-48-like-producing K. pneumoniae isolates. Isolates carrying these carbapenemase are mostly multidrug-resistant. Control strategies based on these genotypic distributions and antimicrobial susceptibilities of CPE isolates are required.

A Conversation with John Bissell

A Conversation with John Bissell

Industrial Biotechnology is Firing on All Cylinders

Industrial Biotechnology is Firing on All Cylinders

Examining the Effects of the Sacramento Dockless E-Bike Share on Bicycling and Driving

One way cities are looking to promote bicycling is by providing publicly or privately operated bike-share services, which enable individuals to rent bicycles for one-way trips. Although many studies have examined the use of bike-share services, little is known about how these services influence individual-level travel behavior more generally. In this study, we examine the behavior of users and non-users of a dockless, electric-assisted bike-share service in the Sacramento region of California. This service, operated by Jump until suspended due to the coronavirus pandemic, was one of the largest of its kind in the U.S., and spanned three California cities: Sacramento, West Sacramento, and Davis. We combine data from a repeat cross-sectional before-and-after survey of residents and a longitudinal panel survey of bike-share users with the goal of examining how the service influenced individual-level bicycling and driving. Results from multilevel regression models suggest that the effect of bike-share on average bicycling and driving at the population level is likely small. However, our results indicate that people who have used-bike share are likely to have increased their bicycling because of bike-share.

Project Spotlight: All–precast concrete design gives Stanford student housing traditional campus look

The Escondido Village Graduate Residences at Stanford University in Palo Alto, Calif., comprise four graduate housing buildings. A creative solution was used to replace the seismic joints and maintain the campus’s traditional architecture look. To meet the university’s requirements, the architect opted for precast concrete. Clark Pacific of West Sacramento, Calif., was selected for the job.

Behind closed doors: What happens when pharmacies close?

Behind closed doors: What happens when pharmacies close?

Distributed Acoustic Sensing Using Dark Fiber for Near-Surface Characterization and Broadband Seismic Event Detection

We present one of the first case studies demonstrating the use of distributed acoustic sensing deployed on regional unlit fiber-optic telecommunication infrastructure (dark fiber) for broadband seismic monitoring of both near-surface soil properties and earthquake seismology. We recorded 7 months of passive seismic data on a 27 km section of dark fiber stretching from West Sacramento, CA to Woodland, CA, densely sampled at 2 m spacing. This dataset was processed to extract surface wave velocity information using ambient noise interferometry techniques; the resulting VS profiles were used to map both shallow structural profiles and groundwater depth, thus demonstrating that basin-scale variations in hydrological state could be resolved using this technique. The same array was utilized for detection of regional and teleseismic earthquakes and evaluated for long period response using records from the M8.1 Chiapas, Mexico 2017, Sep 8th event. The combination of these two sets of observations conclusively demonstrates that regionally extensive fiber-optic networks can effectively be utilized for a host of geoscience observation tasks at a combination of scale and resolution previously inaccessible.

Bayer, Ginkgo launch microbe company

Bayer and Ginkgo Bioworks are forming a company to exploit the potential of synthetic biology to improve microbes that help plants grow. The as yet unnamed firm launches with a $100 million investment from the parent companies and Viking Global Investors. Plants such as soybeans, peas, and peanuts benefit from symbiotic microbes that fix nitrogen from the air and make it available to plant roots. The new company seeks to boost the abilities of these microbes. It will be based at Gingko’s Boston labs and the West Sacramento, Calif., home of Bayer’s plant biologic activities.

Project Spotlight: Resilient city hall annex in California uses hybrid moment frame design

The City Hall Annex in Roseville, Calif., features an earthquake-resistant precast concrete hybrid moment frame design manufactured and installed by West Sacramento, Calif.–based Clark Pacific.

Fusobacterium Isolates Recovered From Colonic Biopsies of Inflammatory Bowel Disease Patients in Korea.

Dear Editor, Inflammatory bowel diseases (IBDs) such as Crohn's disease (CD) and ulcerative colitis (UC) are chronic relapsing inflammatory disorders of the intestine that are characterized by abdominal pain and diarrhea [1,2]. The incidence of IBD is increasing globally and has also increased in Korea recently [2,3]. Although the etiology is unknown, the relationship between the colonic microbiota and IBD has been indicated as a possible contributor. Fusobacterium varium and F. nucleatum have emerged as compelling candidates responsible for IBD exacerbation [4,5]. The colonization by these strains is possibly a useful biomarker for diagnosing gastrointestinal diseases [5]. We aimed to determine the prevalence of Fusobacterium spp. from colonic biopsies of IBD patients in Korea. All 54 patients fulfilling the diagnostic criteria for IBD including 26 of CD, 25 of UC, or 3 of Behcet's disease (BD), at Hanyang University Guri Hospital between June 2014 and June 2015 were included in this study. Among them, 41 (76%) were male. The patient ages ranged from 14 to 75 yr (median: 31 yr). The Institutional Review Board of Hanyang University Guri Hospital approved this study. Biopsy material was obtained from patients undergoing colonoscopy for assessment of IBD status or for confirmation of gastrointestinal disease. Tissues were put into pre-reduced phosphate-buffered saline and immediately transported to the laboratory for bacterial culture. The specimens were ground, inoculated on crystal violet erythromycin (CVE) agar supplemented with tryptophan, and incubated at 37℃ for 48 hr in an anaerobic jar [6]. All isolates showing a different colony morphology were identified by 16S rRNA gene sequencing by using PCR predicted to yield a product of 1,300 bp [7]. The PCR conditions were as follows: 95℃ for 5 min; 30 cycles at 95℃ for 30 sec, 55℃ for 30 sec, and 72℃ for 1 min; and a final 10-min step at 72℃. The sequencing of the amplification products were performed in a commercial facility (Macrogen, Seoul, Korea). The sequencing analysis was completed using the GenBank and EzTaxon databases. Some strains were identified using the MicroScan WalkAway automated system (Dade Behring, West Sacramento, CA, USA) and the Vitek MS system (bioMerieux, Marcy l'Etoile, France). Ten Fusobacterium isolates were recovered from nine of the 54 patients as follows: six F. mortiferum, two F. varium, and one F. nucleatum and F. mortiferum (Table 1). Table 1 Fusobacterium species and other bacteria isolated from nine patients, identified by using 16S rRNA gene sequencing Clinically, the most important Fusobacterium species are F. nucleatum and F. necrophorum, but F. ulcerans and the F. mortiferum–F. varium group have occasionally been isolated from human. Ohkusa et al. [4] suggested that F. varium might be one of the elusive pathogenic factors in UC. In addition, Strauss et al. [5] reported that an F. nucleatum strain isolated from IBD tissues was more invasive than strains isolated from normal tissues. A correlation between UC and colonization with F. varium has also been noted in a cohort of Japanese patients [4]. F. nucleatum has been linked to colorectal cancer as well as IBD, which has been recognized as a risk factor of colorectal cancer [8]. Fusobacterium spp. were isolated from 63.6% and 53.1% of IBD patients in Canada and Japan, where F. nucleatum was more prevalent in the Canadian patients (43%) than in the Japanese patients (4%) [5,9]. The prevalence of Fusobacterium in our study cohort was 17%, which was lower than that in Canada and Japan. There were limitations of our study that could have affected the low recovery rate. First, whereas we allowed only two days of incubation time for anaerobic culture, Strauss et al. [5] allowed five days. Hence, it was possible that some Fusobacterium spp. were lost owing to early termination of the incubation. Furthermore, with a longer incubation time, the anaerobic chamber may be more optimal than the anaerobic jar that we used. Second, for the specific recovery of Fusobacterium spp. from clinical specimens, the josamycin, vancomycin, and norfloxacin in JVN agar are better than the CVE agar that we used [10]. Further studies are necessary because of our small sample size and the absence of strains isolated from healthy controls. Although it is not possible to draw any strong conclusions from this small data subset, it is likely that there are differences of isolated species according to the country of origin, supporting the notion that no single bacterial species is a biomarker of IBD. In conclusion, this study is the first attempt to assess the prevalence of Fusobacterium spp. in colonic tissues of IBD patients in Korea, revealing that only 17% of the patients carried species of this genus.

Evaluation of Verigene Blood Culture Test Systems for Rapid Identification of Positive Blood Cultures.

The performance of molecular tests using the Verigene Gram-Positive and Gram-Negative Blood Culture nucleic acid tests (BC-GP and BC-GN, resp.; Naosphere, Northbrook, IL, USA) was evaluated for the identification of microorganisms detected from blood cultures. Ninety-nine blood cultures containing Gram-positive bacteria and 150 containing Gram-negative bacteria were analyzed using the BC-GP and BC-GN assays, respectively. Blood cultures were performed using the Bactec blood culture system (BD Diagnostic Systems, Franklin Lakes, NJ, USA) and conventional identification and antibiotic-susceptibility tests were performed using a MicroScan system (Siemens, West Sacramento, CA, USA). When a single strain of bacteria was isolated from the blood culture, Verigene assays correctly identified 97.9% (94/96) of Gram-positive bacteria and 93.8% (137/146) of Gram-negative bacteria. Resistance genes mecA and vanA were correctly detected by the BC-GP assay, while the extended-spectrum β-lactamase CTX-M and the carbapenemase OXA resistance gene were detected from 30 cases cultures by the BC-GN assay. The BC-GP and BC-GN assays showed high agreement with conventional identification and susceptibility tests. These tests are useful for rapid identification of microorganisms and the detection of clinically important resistance genes from positive Bactec blood cultures.

From Hopelessness to Expectation: An Interview with Christopher Cabaldon, Mayor of West Sacramento

Christopher Cabaldon is the mayor of West Sacramento, a small town just over the river from California’s capital city, Sacramento. Mayor Cabaldon received his Master of Public Policy and Administration (MPPA) in 1994 as part of the inaugural class of the program at California State University, Sacramento. He first became mayor of West Sacramento in 1998, and he was the first mayor directly elected by the citizens of West Sacramento in 2004.West Sacramento is growing rapidly. Since 2000, the population has increased by over 50 percent, nearly reaching 50,000 at the time of the 2010 US Census. Changes in West Sacramento have come from the development of Southport, a new master-planned residential neighborhood on the south side of the city, as well as infill development in the center of town and in established neighborhoods. Retail has also moved into West Sacramento where there previously had been very little, anchored by Ikea and Target. In 2000, the River Cats, a minor league baseball team, came to town and moved into a new stadium in West Sacramento.On March 13, Mayor Cabaldon spoke with Monika Jansen of Policy Perspectives over the phone to discuss his MPPA, executive leadership and democracy at the city level, his TEDx Talk from 2014, and his vision for West Sacramento.

Antimicrobial drug-resistant bacteria isolated from Syrian war-injured patients, August 2011-March 2013.

Antimicrobial drug-resistant bacteria isolated from Syrian war-injured patients, August 2011-March 2013.

Abstract LB-32: Patient-derived xenograft (PDX) paraclinical platform to guide precision medicine in urothelial cancer

Abstract BACKGROUND: The overall efficiency in personalizing medicine by pairing targeted therapy with specific genomic alterations identified through omics technologies is disappointing as current computational biology methods have difficulty in distinguishing “driver” alterations from “passenger” ones. We have developed PDXs that share essentially the same genetic background as the parental human cancer, and use this platform to screen for most effective drugs and perform mechanistic study of drug resistance in order to guide design of precision medicine in urothelial cancer. MATERIALS AND METHODS: PDXs were developed by direct implantation of fresh clinical tumor specimens in immunocompromised NSG mice (The Jackson Laboratory, West Sacramento, CA). Whole exome, transcriptome and microRNA sequencing was performed, followed by computational biological analysis to identify druggable genetic alterations that were further validated with immunofluorescence (IF) and immunohistochemical (IHC) staining. Efficacy tests to determine response to treatment by targeted therapy, together with analyses to determine the mechanisms of resistance were performed in NSG mice carrying PDXs. RESULTS: The engraftment rate of PDX was 41 % (13/42). The fidelity between the PDXs and the parental patient cancers was confirmed with cell morphology, tissue microarray IHC/IF staining and mutation profiles. Cell morphology was maintained during passaging in both the subcutaneous and orthotopic PDXs. All PDXs had multiple druggable genetic alterations. Of the first 8 PDXs, 2 harbored PIK3CA mutations (H1047R at the kinase domain and D549Y at the helical domain); 5 had ERBB2 mRNA overexpression determined by transcriptome sequencing, and protein overexpression (3+ by IHC), and 5 had EphB4 overexpression. sEphB4-HSA is an experimental drug developed by Gill (co-author). In PDXs overexpressing EphB4, blockade of EphB4 with sEphB4-HSA significantly prolonged the progression-free survival (PFS) from 9.5 days in the control group to 16.7 days (p=3.17 X 10e-5). Western blot, IHC, and deep sequencing analyses in PDX tissue specimens collected before/during treatment, and after the development of resistance were used to determine the mechanism of resistance. CONCLUSION: PDXs can potentially serve as a para-clinical model for drug efficacy screening, study of resistance mechanisms, and drug development. Citation Format: Chong-xian Pan, Hongyong Zhang, Clifford Tepper, Paramita Ghosh, Sheri Kuslak-Meyer, Susie Airhart, Parkash Gill, David Gandara, Edison Liu, Ralph de Vere White. Patient-derived xenograft (PDX) paraclinical platform to guide precision medicine in urothelial cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-32. doi:10.1158/1538-7445.AM2014-LB-32

Anatomic sites of colonization with community-associated methicillin-resistant Staphylococcus aureus.

Anatomic sites of colonization with community-associated methicillin-resistant Staphylococcus aureus.

Light Chain of Factor VIII Is Sufficient for Accelerating Cleavage of von Willebrand Factor by ADAMTS13 Metalloprotease

We previously demonstrated that coagulation factor VIII (FVIII) accelerates proteolytic cleavage of von Willebrand factor (VWF) by A disintegrin and metalloprotease with thrombospondin type 1 repeats (ADAMTS13) under fluid shear stress. In this study, the structural elements of FVIII required for the rate-enhancing effect and the biological relevance of this cofactor activity are determined using a murine model. An isolated light chain of human FVIII (hFVIII-LC) increases proteolytic cleavage of VWF by ADAMTS13 under shear in a concentration-dependent manner. The maximal rate-enhancing effect of hFVIII-LC is ∼8-fold, which is comparable with human full-length FVIII and B-domain deleted FVIII (hFVIII-BDD). The heavy chain (hFVIII-HC) and the light chain lacking the acidic (a3) region (hFVIII-LCΔa3) have no effect in accelerating VWF proteolysis by ADAMTS13 under the same conditions. Although recombinant hFVIII-HC and hFVIII-LCΔa3 do not detectably bind immobilized VWF, recombinant hFVIII-LC binds VWF with high affinity (K(D), ∼15 nM). Moreover, ultra-large VWF multimers accumulate in the plasma of fVIII(-/-) mice after hydrodynamic challenge but not in those reconstituted with either hFVIII-BDD or hFVIII-LC. These results suggest that the light chain of FVIII, which is not biologically active for clot formation, is sufficient for accelerating proteolytic cleavage of VWF by ADAMTS13 under fluid shear stress and (patho) physiological conditions. Our findings provide novel insight into the molecular mechanism of how FVIII regulates VWF homeostasis.

ESBL-Positive Enterobacteria Isolates in Drinking Water

To the Editor: Extended-spectrum β-lactamase (ESBL)–producing members of the family Enterobacteriaceae (enterobacteria) are a worldwide problem (1), but little data are available from central Africa (2). In recent years, ESBL-producing Enterobacteriaceae isolates have shifted from the hospital to the community and the environment (1). The aim of this study was to assess the presence of ESBL-producing Enterobacteriaceae isolates in sachet-packaged water bags sold as drinking water in the streets of Kinshasa, the capital of Democratic Republic of the Congo. In November 2009 and June 2010, a total of 101 sachet-packaged water bags were bought from street vendors in 9 of 24 municipalities (covering residential areas and slums) of the city of Kinshasa. The bags were transported in ice coolers and processed within 4 hours of collection. We filtered 100 mL of each sample through 0.45-µm pore size filters (Sartorius, Goettingen, Germany). The filters were then transferred to an agar plate containing mEndoLES agar (Difco, Franklin Lakes, NJ, USA) and incubated at 35°C for 24 hours. Growing colonies were subcultured on Kligler iron agar (Oxoid, Cambridge, UK), and gram-negative glucose-fermenting isolates were identified to the species level and assessed for antimicrobial drug susceptibility with Microscan NBC42 panels (Siemens Healthcare Diagnostics Inc., West Sacramento, CA, USA). Isolates labeled by Microscan as ESBL producers were confirmed by the double-disk method, which compared 1 disk containing cefotaxime with 1 disk containing cefotaxime and clavulanic acid and 1 disk containing ceftazidime with 1 disk containing ceftazidime and clavulanic acid (Rosco Diagnostica, Taastrup, Denmark), according to the Clinical and Laboratory Standards Institute guidelines (3). We used Escherichia coli ATCC 25922 and Klebsiella pneumoniae ATCC 700603 as control strains. Detection and identification of ESBL-producing bla genes were carried out by using a commercial multiplex ligation PCR microarray CT 101 (Check-Points Health BV, Wageningen, the Netherlands) (4). A total of 101 sachet-packaged water bags were purchased at random from different vendors: 88 sealed and branded bags (of 68 different brands) and 13 hand-tied unbranded bags. The precise origin of the water could not be determined because vendors are unlicensed resellers and most producers are not registered. Water bags lacked essential information such as contact addresses, batch number, and production and expiration dates. Because we also observed empty branded sheets of bags for sale on the market, we assumed that many of the branded bags are simply filled with tap water or water from other supplies without any prior treatment. None of the water bags tested for chlorine (36 of 101) contained free chlorine levels >0.1 mg/L. Nearly one third of the water bags were contaminated with Enterobacteriaceae isolates (22/88 branded bags and 9/13 hand-tied bags). The bags were obtained in townships and residential quarters. Overall, 150 nonduplicate Enterobacteriaceae isolates were recovered. The main species were K. pneumoniae (56.0% of isolates found in 23/101 of water bags) and Enterobacter spp. (30.6%, in 20/101 water bags); Citrobacter spp. accounted for 4.7% of isolates and E. coli for 3.3%. Eight isolates (5.3 %) were confirmed as ESBL producers by antimicrobial drug susceptibility tests, and they were recovered from 2 branded and 2 hand-tied bags. The species, microarray results, and the associated drug resistance are listed in the Table. Five isolates carried blaCTX-M genes belonging to CTX-M1 group, and 3 isolates carried blaSHV variants. No TEM-ESBL genes were detected. On the basis of checkpoint results and previously validated data, we further categorized the SHV G238S mutation as SHV-2-like and the double SHV G238A + SHV E240K mutation as SHV-18 (5). Table ESBL-producing Enterobacteriaceae recovered from sachet-packaged water bags in Kinshasa, Democratic Republic of the Congo* ESBL-producing Enterobacteriaceae isolates constitute a major public health concern in industrialized and resource-poor settings. Few reports are available from Africa, although hospital-associated ESBL producers have been described in Cameroon and the Central African Republic (6,7). ESBL-producing bacteria have been recovered from different sources in the community, including food and companion animals (8,9), and 1 recent study from India reported that a substantial number of tap water samples were contaminated with carbapenemase blaNDM-1 producing organisms (10). Kinshasa is the second-largest city in sub-Saharan Africa. In 2008, of its estimated 8.7 million inhabitants, only 46%had access to safe drinking water, and 23% had access to improved sanitation facilities according to the World Bank. Opportunistic pathogens in drinking water and poor sanitary conditions may increase the risk of developing infectious enterocolitis for consumers, especially for those who are immunocompromised. It can eventually lead to chronic intestinal carriage of multidrug-resistant organisms. The presence of ESBL producers in the intestinal flora could also lead to horizontal transfer of drug resistance genes from commensal flora to enteric pathogens. This emergence of ESBL-producing bacteria and further community-associated infections poses a public threat, especially in low-resource countries where surveillance is suboptimal and empiric treatment of invasive infections often includes third-generation cephalosporins.

Epigenetic Regulation of Cancer Stem Cell Genes in Triple-Negative Breast Cancer

Expression of specific breast cancer stem cells (BCSCs) is seen in aggressive tumors, but their regulation is unclear. Epigenetic changes influence gene expression and are implicated in breast cancer progression. We hypothesized that promoter methylation regulates specific BCSC-related genes [CD44, CD133, CD24, MSH1 (alias, Musashi-1), and ALDH1] and that this epigenetic profile can identify aggressive subtypes, such as triple-negative breast cancer (TNBC). Methylation analysis was performed using MassARRAY EpiTYPER sequencing; CpG-rich sites were identified in the promoter regions of BCSC genes, except ALDH1. These sites were screened by treatment with 5-aza-2'-deoxycytidine in four TN and five non-TNBC cell lines. The specific regulatory CpG site demonstrating the most significant inverse correlation between CpG site methylation and mRNA expression was identified for CD44, CD133, and Musashi-1, but not for CD24. Methylation of CD44, CD133, and Musashi-1 was evaluated in 91 American Joint Committee on Cancer stage I to III primary breast cancer tumors, and these sites were significantly hypomethylated in TNBC versus non-TNBC. The IHC staining of primary tumors with the highest and lowest methylation levels revealed the strongest staining in hypomethylated specimens, suggesting that hypomethylation leads to gene activation. We demonstrate that methylation is a significant mechanism regulating CD44, CD133, and Musashi-1, and that gene hypomethylation correlates with TNBC. Assessment of epigenetic changes in BCSC genes may provide a more accurate classification of TNBC and could be developed as potential therapeutic targets.

Roles for Peroxisome Proliferator-activated Receptor γ (PPARγ) and PPARγ Coactivators 1α and 1β in Regulating Response of White and Brown Adipocytes to Hypoxia

Obese white adipose tissue is hypoxic but is incapable of inducing compensatory angiogenesis. Brown adipose tissue is highly vascularized, facilitating delivery of nutrients to brown adipocytes for heat production. In this study, we investigated the mechanisms by which white and brown adipocytes respond to hypoxia. Brown adipocytes produced lower amounts of hypoxia-inducible factor 1α (HIF-1α) than white adipocytes in response to low O(2) but induced higher levels of hypoxia-associated genes. The response of white adipocytes to hypoxia required HIF-1α, but its presence alone was incapable of inducing target gene expression under normoxic conditions. In addition to the HIF-1α targets, hypoxia also induced many inflammatory genes. Exposure of white adipocytes to a peroxisome proliferator-activated receptor γ (PPARγ) ligand (troglitazone) attenuated induction of these genes but enhanced expression of the HIF-1α targets. Knockdown of PPARγ in mature white adipocytes prevented the usual robust induction of HIF-1α targets in response to hypoxia. Similarly, knockdown of PPARγ coactivator (PGC) 1β in PGC-1α-deficient brown adipocytes eliminated their response to hypoxia. These data demonstrate that the response of white adipocytes requires HIF-1α but also depends on PPARγ in white cells and the PPARγ cofactors PGC-1α and PGC-1β in brown cells.