• O-GlcNAcylation and oxidation of proteins: is signalling in the cardiovascular system becoming sweeter?

      Lima, Victor V.; Spitler, Kathryn M.; Choi, Hyehun; Webb, R. Clinton; Tostes, Rita C.; Department of Physiology (2012-10-1)
      O-GlcNAcylation is an unusual form of protein glycosylation, where a single-sugar [GlcNAc (N-acetylglucosamine)] is added (via β-attachment) to the hydroxyl moiety of serine and threonine residues of nuclear and cytoplasmic proteins. A complex and extensive interplay exists between O-GlcNAcylation and phosphorylation. Many phosphorylation sites are also known glycosylation sites, and this reciprocal occupancy may produce different activities or alter the stability in a target protein. The interplay between these two post-translational modifications is not always reciprocal, as some proteins can be concomitantly phosphorylated and O-GlcNAcylated, and the adjacent phosphorylation or O-GlcNAcylation can regulate the addition of either moiety. Increased cardiovascular production of ROS (reactive oxygen species), termed oxidative stress, has been consistently reported in various chronic diseases and in conditions where O-GlcNAcylation has been implicated as a contributing mechanism for the associated organ injury/protection (for example, diabetes, Alzheimer's disease, arterial hypertension, aging and ischaemia). In the present review, we will briefly comment on general aspects of O-GlcNAcylation and provide an overview of what has been reported for this post-translational modification in the cardiovascular system. We will then specifically address whether signalling molecules involved in redox signalling can be modified by O-GlcNAc (O-linked GlcNAc) and will discuss the critical interplay between O-GlcNAcylation and ROS generation. Experimental evidence indicates that the interactions between O-GlcNAcylation and oxidation of proteins are important not only for cell regulation in physiological conditions, but also under pathological states where the interplay may become dysfunctional and thereby exacerbate cellular injury.
    • Object recognition in clutter: cortical responses depend on the type of learning

      Hegéd, Jay; Thompson, Serena K.; Brady, Mark; Kersten, Daniel; Department of Ophthalmology; Vision Discovery Institute; Brain & Behavior Discovery Institute (2012-06-19)
      Theoretical studies suggest that the visual system uses prior knowledge of visual objects to recognize them in visual clutter, and posit that the strategies for recognizing objects in clutter may differ depending on whether or not the object was learned in clutter to begin with. We tested this hypothesis using functional magnetic resonance imaging (fMRI) of human subjects. We trained subjects to recognize naturalistic, yet novel objects in strong or weak clutter. We then tested subjects' recognition performance for both sets of objects in strong clutter. We found many brain regions that were differentially responsive to objects during object recognition depending on whether they were learned in strong or weak clutter. In particular, the responses of the left fusiform gyrus (FG) reliably reflected, on a trial-to-trial basis, subjects' object recognition performance for objects learned in the presence of strong clutter. These results indicate that the visual system does not use a single, general-purpose mechanism to cope with clutter. Instead, there are two distinct spatial patterns of activation whose responses are attributable not to the visual context in which the objects were seen, but to the context in which the objects were learned.
    • Online Teaching

      Barefield, Amanda; Department of Health Management and Informatics (2016-10-24)
      "Have you ever wandered what it would be like to teach online, or do you cringe at the sound of the words? In this session, Dr. Barefield will share insights from her 15+ years of teaching in an online environment. Topics of discussion will include learning in the 21st century, planning an online course, developing the online course, and teaching the online course. Whether you are a newby or old pro, there will be something for everyone to discuss." Ms. Barefield has 20 years experience teaching in hybrid and online environments. She received her EdD in Instructional Technology and Distance Education from Nova Southeastern University. Her research includes evaluating student support services in online environments and comparisons of student performance in traditional and online environments. She currently teaches in both traditional and online formats for the Health Information Administration and Master of Public Health Programs.
    • ONTOGENETIC CHANGES OF PROTEINS OF ENDOPLASMIC RETICULUM

      Black, Owen; Bresnick, Edward; Department of Cellular Biology and Anatomy (1972-03-1)
      The proteins of the smooth and rough endoplasmic reticulum from fetal, immature, and adult male rats were compared after incorporation of two radioactively labeled precursors, 14C-labeled amino acids and δ-aminolevulinic acid-3H by means of gel electrophoresis. The labeling patterns indicated that protein components present in two major electrophoretic bands underwent significant synthesis in fetal tissue while three actively incorporating protein bands were noted in adult tissue. Although the uptake of the amino acids-14C decreased for the smooth and rough elements of the endoplasmic reticulum as a whole during liver development, the qualitative patterns were not significantly different in adult and fetal livers. The over-all incorporation (disintegrations per minute per milligram protein) of the heme precursor into the smooth and rough elements also did not change with development. However, a change was noted in the distributional electrophoretic patterns with development. The estimation of molecular weight (by disc electrophoresis) and the incorporation of the heme precursor suggested the similarity of the two major protein bands to cytochrome P-450 and cytochrome b5, components of the endoplasmic reticulum, thought to be involved in the mixed-function oxidase system. The evidence indicated that in fetal liver, at a time when the oxidase capability was low, the amino acid incorporation into these two protein groups was the same as in the adult. The incorporation of the heme moiety, however, was different, decreasing in the cytochrome b5 region and increasing in the cytochrome P-450 region during development. These results correlate with the increase in oxidase activity associated with liver development.
    • Ontological Differences in First Compared to Third Trimester Human Fetal Placental Chorionic Stem Cells

      Jones, Gemma N.; Moschidou, Dafni; Puga-Iglesias, Tamara-Isabel; Kuleszewicz, Katarzyna; Vanleene, Maximilien; Shefelbine, Sandra J.; Bou-Gharios, George; Fisk, Nicholas M.; David, Anna L.; De Coppi, Paolo; et al. (2012-09-4)
      Human mesenchymal stromal/stem cells (MSC) isolated from fetal tissues hold promise for use in tissue engineering applications and cell-based therapies, but their collection is restricted ethically and technically. In contrast, the placenta is a potential source of readily-obtainable stem cells throughout pregnancy. In fetal tissues, early gestational stem cells are known to have advantageous characteristics over neonatal and adult stem cells. Accordingly, we investigated whether early fetal placental chorionic stem cells (e-CSC) were physiologically superior to their late gestation fetal chorionic counterparts (l-CSC). We showed that e-CSC shared a common phenotype with l-CSC, differentiating down the osteogenic, adipogenic and neurogenic pathways, and containing a subset of cells endogenously expressing NANOG, SOX2, c-MYC, and KLF4, as well as an array of genes expressed in pluripotent stem cells and primordial germ cells, including CD24, NANOG, SSEA4, SSEA3, TRA-1-60, TRA-1-81, STELLA, FRAGILIS, NANOS3, DAZL and SSEA1. However, we showed that e-CSC have characteristics of an earlier state of stemness compared to l-CSC, such as smaller size, faster kinetics, uniquely expressing OCT4A variant 1 and showing higher levels of expression of NANOG, SOX2, c-MYC and KLF4 than l-CSC. Furthermore e-CSC, but not l-CSC, formed embryoid bodies containing cells from the three germ layer lineages. Finally, we showed that e-CSC demonstrate higher tissue repair in vivo; when transplanted in the osteogenesis imperfecta mice, e-CSC, but not l-CSC increased bone quality and plasticity; and when applied to a skin wound, e-CSC, but not l-CSC, accelerated healing compared to controls. Our results provide insight into the ontogeny of the stemness phenotype during fetal development and suggest that the more primitive characteristics of early compared to late gestation fetal chorionic stem cells may be translationally advantageous.
    • Open-magnet MR defaecography compared with evacuation proctography in the diagnosis and management of patients with rectal intussusception

      Ahn, Elizabeth; Davila, Alec; Heneidi, Saleh; Mohamed, Mohamed; Rahim, Tayeb; Thakkar, Nancy (2015-03-09)
      For patients with rectal intussusception, will the use of open-magnet magnetic resonance (MR) defaecography in addition to evacuation proctography (EP) result in better diagnosis and management?
    • Operant Responding for Alcohol: A Specially Bred Animal Model of Anxiety and Alcohol Use Disorder

      Berg, Warren S.C.; Department of Psychological Sciences (Augusta University, 2017-05)
      Alcohol abuse and dependence affects a significant portion of the United States population. In America alone, approximately 17 million adults ages 18 and older and an estimated 855,000 adolescents ages 12-meet diagnostic criteria for addiction (National Institute of Alcohol Abuse and Alcoholism, 2016). In order to be diagnosed with an alcohol use disorder (AUD), an individual must meet specific criteria detailed in the Diagnostic and Statistical Manual of Mental Disorders (DSM). According to the most recent edition (DSM–5), a person meeting at least two of 11 criteria during a 12-month period meets the diagnostic criteria for an AUD (American Psychiatric Association, 2013). The severity of an AUD—mild, moderate, or severe—is based on the number of criteria met (see Appendix B for a list of the 11 diagnostic criteria for AUD). Unfortunately, not everyone seeks assistance for their addiction. According to a report published in 2015 by the Substance Abuse and Mental Health Services Administration (SAMHSA), fewer than 10% of individuals with an AUD received treatment at a specialized facility. Thus, this is a very serious health concern. Furthermore, there is no guarantee that those who do receive treatment will get better. That is, despite extensive research on the etiology of AUD, high incidence, low treatment numbers, and broad treatment methodologies, researchers and clinicians have a tenuous understanding of this disorder at best. [Introduction]
    • Operant Sensation Seeking Requires Metabotropic Glutamate Receptor 5 (mGluR5)

      Olsen, Christopher M.; Childs, Daniel S.; Stanwood, Gregg D.; Winder, Danny G.; Tsien, Joe Z.; Department of Neurology; College of Graduate Studies (2010-11-30)
      Pharmacological and genetic studies have suggested that the metabotropic glutamate receptor 5 (mGluR5) is critically involved in mediating the reinforcing effects of drugs of abuse, but not food. The purpose of this study was to use mGluR5 knockout (KO), heterozygous (Het), and wildtype (WT) mice to determine if mGluR5 modulates operant sensation seeking (OSS), an operant task that uses varied sensory stimuli as a reinforcer. We found that mGluR5 KO mice had significantly reduced OSS responding relative to WT mice, while Het mice displayed a paradoxical increase in OSS responding. Neither KO nor Het mice exhibited altered operant responding for food as a reinforcer. Further, we assessed mGluR5 KO, Het and WT mice across a battery of cocaine locomotor, place preference and anxiety related tests. Although KO mice showed expected differences in some locomotor and anxiety measures, Het mice either exhibited no phenotype or an intermediate one. In total, these data demonstrate a key role for mGluR5 in OSS, indicating an important role for this receptor in reinforcement-based behavior.
    • Opioid Crisis Trends in Georgia: Using Data Management Systems to Better Inform Public Policy

      Sheikh, Nafiz; Tauhidul, Liniya; Medical College of Georgia
      Introduction: The nationwide opioid epidemic is arguably the most consequential public health crisis of the new millennium. Unfortunately, a dearth of medical literature exists analyzing the scope of the epidemic in Georgia. This presentation will investigate trends in fatal opioid overdoses in Georgia using a robust healthcare data management system: Center for Disease Control’s (CDC) WONDER. Methods: Using CDC WONDER, a cohort of all fatal opioid overdoses in Georgia from 1999 – 2017 was obtained (N=10,070). The group was then stratified by race, sex, age group, and overdosed opioid type. Time series analyses were used to determine trends, two-sided Chi-square tests with statistical significance set to p<0.05 used to compare opioid mortality proportions from different years and mortalities between age groups. Lastly findings were correlated to geography to ascertain if urbanization correlated to opioid mortality. Results: Approximately 1056 fatal opioid overdoses occurred in 2017, up 192% from 550 deaths in 2010. Fatal overdoses from heroin and synthetic accounted for only 2% and 17% of total deaths in 2010 but magnified to 20% and 32% by 2017 (p<0.05). Beginning 2013, heroin and synthetic opioids such as fentanyl together drove Georgia opioid mortality sharply higher. Among different age groups, Georgians aged 25-34yrs experienced the highest mortalities compared to other females within the same age group (p<0.05) and to males and female in the 35-44yrs and 45-54yrs groups (p<0.05). Correlating fatalities to geography found urban areas in Atlanta, Augusta, and Columbus to have the highest mortality rates. Conclusion: Georgians have experienced an unprecedented surge in mortality from opioid-related overdoses in recent years. With robust healthcare data management systems, however, new research endeavors are poised to generate more thorough epidemiological reports that will better inform local and state health policy.
    • OPTIMIZED ISOLATION AND QUANTIFICATION OF IN VIVO DISTRIBUTION OF EXOSOMES FOR POTENTIAL TARGETED THERANOSTIC APPLICATION

      Rashid, Mohammad Harun; Department of Biochemistry and Molecular Biology (Augusta University, 2019-07)
      Exosomes are critical mediators of intercellular crosstalk and regulators of the cellular/tumor microenvironment. Exosomes have great prospects for clinical application as a theranostic and prognostic probe. Nevertheless, the advancement of exosome research has been thwarted by our limited knowledge of the most efficient isolation method and the in vivo trafficking. Here we have shown that a combination of two size-based methods using a 0.20 μm syringe filter and 100k centrifuge membrane filter followed by ultracentrifugation yields a greater number of uniform exosomes compared to other available methods. We demonstrated the visual representation and quantification of the differential in vivo distribution of radioisotope 131I-labeled exosomes from diverse cellular origins, e.g., tumor cells with or without treatments, myeloid-derived suppressor cells and endothelial progenitor cells. We also determined that the distribution was dependent on the exosomal protein/cytokine contents. Further, we also generated engineered exosomes expressing precision peptide for targeting CD206 positive M2-macrophages. M2-macrophages participate in immune suppression, epithelial to mesenchymal transition, invasion, angiogenesis, tumor progression and subsequent metastasis foci formation. Given their pro-tumorigenic function and prevalence in most malignant tumors with lower survival, early in vivo detection and intervention of M2-macrophages may boost the clinical outcome. To determine in vivo distribution of M2-macrophages, we adopted 111In-oxine based radiolabeling of the targeted exosomes and SPECT. When injected these radiolabeled targeted exosomes into 4T1 breast tumor-bearing mice, exosomes accumulated at the periphery of the primary tumor, metastatic foci in the lungs, in the spleen, and liver. Ex vivo quantification of radioactivity also showed similar distribution. Injected DiI dye-labeled exosomes into the same mice showed the adherence of exosomes to the CD206 positive macrophages on ex vivo fluorescent microscopy imaging, confirming the targeting efficacy of the exosomes. In addition, we utilized these engineered exosomes to carry the Fc portion of mouse IgG2b with the intention of augmenting antibody-dependent cell-mediated cytotoxicity. We have auspiciously demonstrated that M2-macrophage targeting therapeutic exosomes deplete M2-macrophages both in vitro and in vivo, and reduce tumor burden in a metastatic breast cancer model. The applied in vivo imaging modalities can be utilized to monitor disease progression, metastasis, and exosome-based targeted therapy.
    • Optimizing Isolation and Culture of Primary Microglia

      Doughty, Deanna; Department of Biological Sciences (Augusta University, 2018-12)
      Glioblastoma (GBM) is the most aggressive and common adult brain tumor subtype, with the majority of patients surviving less than one year. The GBM microenvironment is composed of tumor cells as well as non-cancerous cells, such as microglia, a component of the immune system in the brain. To better understand the role of microglia in GBM, we have optimized in vitroculture conditions for primary microglia. Growing microglia in culture is challenging, but this technique is needed for planned future experiments. Microglia were isolated from mouse neuronal tissue by magnetic bead antibody cell separation using the cellular marker CX3CR1. Isolated microglia were then cultured in various culture conditions, and cellular morphology by light microscopy was used to determine cell health, viability, and activation status. It was determined that the primary microglia grow best in neurobasal media in wells coated with poly-D lysine. Future studies aim to isolate a larger number of cells to allow forco-culture of the inactivated microglia with GBM cells. These results will allow us to better understand the role that microglia play in GBM progression.
    • An ORMOSIL-Containing Orthodontic Acrylic Resin with Concomitant Improvements in Antimicrobial and Fracture Toughness Properties

      Gong, Shi-qiang; Epasinghe, Jeevani; Rueggeberg, Frederick A.; Niu, Li-na; Mettenberg, Donald; Yiu, Cynthia K. Y.; Blizzard, John D.; Wu, Christine D.; Mao, Jing; Drisko, Connie L.; et al. (2012-08-01)
      Global increase in patients seeking orthodontic treatment creates a demand for the use of acrylic resins in removable appliances and retainers. Orthodontic removable appliance wearers have a higher risk of oral infections that are caused by the formation of bacterial and fungal biofilms on the appliance surface. Here, we present the synthetic route for an antibacterial and antifungal organically-modified silicate (ORMOSIL) that has multiple methacryloloxy functionalities attached to a siloxane backbone (quaternary ammonium methacryloxy silicate, or QAMS). By dissolving the water-insoluble, rubbery ORMOSIL in methyl methacrylate, QAMS may be copolymerized with polymethyl methacrylate, and covalently incorporated in the pressure-processed acrylic resin. The latter demonstrated a predominantly contact-killing effect on Streptococcus mutans ATCC 36558 and Actinomyces naselundii ATCC 12104 biofilms, while inhibiting adhesion of Candida albicans ATCC 90028 on the acrylic surface. Apart from its favorable antimicrobial activities, QAMS-containing acrylic resins exhibited decreased water wettability and improved toughness, without adversely affecting the flexural strength and modulus, water sorption and solubility, when compared with QAMS-free acrylic resin. The covalently bound, antimicrobial orthodontic acrylic resin with improved toughness represents advancement over other experimental antimicrobial acrylic resin formulations, in its potential to simultaneously prevent oral infections during appliance wear, and improve the fracture resistance of those appliances.
    • OSTEOPONTIN AS A NOVEL IMMUNE CHECKPOINT

      Klement, John; Department of Biochemistry and Molecular Biology (Augusta University, 2020-05)
      The host adaptive immune system functions to discriminate self from non-self, eliminating threats from viral infection to tumors. Cytotoxic lymphocytes (CTLs) are the primary effector arm of adaptive immunity. To prevent aberrant activation and autoimmunity, immune checkpoints function physiologically to restrain the CTL response. Tumors pathologically express these checkpoints, preventing immune-driven tumor clearance. Accordingly, immune checkpoint inhibitors (ICIs) have shown remarkable clinical success. However, many types of malignancies, as well as many individual patients with responsive tumor types, fail to benefit from current ICI immunotherapies. This conundrum suggests that as-yet undiscovered immune checkpoints exist. We observed that mice deficient in the transcription factor interferon regulatory factor eight (IRF8) tolerated allogenic tumor grafts and demonstrated impaired CTL activation with an accumulation of CD44hi memory-like CTLs. We sought to investigate the mechanism of this immunosuppression. Conditional deletion of IRF8 in T cells, as well as a mixed chimera model, demonstrated that IRF8 did not directly control CTL activation or differentiation into a CD44hi population. Instead, global loss of IRF8 lead to an expansion of an immature myeloid CD11b+Ly6G+Ly6Clo population which highly expressed osteopontin (OPN), a physiological ligand for CD44. Elevated levels of OPN were shown to suppress murine CTL activation and proliferation. A similar IRF8-OPN-CD44 axis was observed in murine and human colorectal cancer, which is refractory to current ICI therapies. Malignant cells and human patients displayed enhanced OPN levels relative to healthy donor controls. This was shown to be mediated by loss of IRF8 expression, which directly bound to the OPN promoter to repress its transcription. Elevated levels of OPN similarly prevented human CTL activation, and higher levels of OPN were correlated with decreased survival in human patients. We have shown that the IRF8-OPN-CD44 axis functions as a novel immune checkpoint in both myeloid and tumor cells. Blockade of OPN may have potent anti-tumor activity, expanding the pool of patients responsive to ICI therapy.
    • Outcomes of Music, Dance, & Movement Interventions for Children with Autism Spectrum Disorder Within the Scope of Occupational Therapy: Scoping Review

      Bankson, Baylee; Cox, Ashlyn; Fulmer, Haley; Hausman, Lydia; Longfellow, Danielle; Department of Occupational Therapy (Augusta University, 2020-08-31)
      At the conclusion of this, attendees will: 1) Identify frequently measured outcomes of using music, dance, and movement-based interventions with individuals with autism spectrum disorder, as identified through a scoping review of the literature and 2) List specific music, dance, or movement-based interventions that are available to OT practitioners working with individuals with autism spectrum disorder (ASD), as identified through a scoping review of the literature.
    • Overt Attention and Context Factors: The Impact of Repeated Presentations, Image Type, and Individual Motivation

      Kaspar, Kai; König, Peter; Tsien, Joe Z.; Department of Neurology; College of Graduate Studies (2011-07-5)
      The present study investigated the dynamic of the attention focus during observation of different categories of complex scenes and simultaneous consideration of individuals' memory and motivational state. We repeatedly presented four types of complex visual scenes in a pseudo-randomized order and recorded eye movements. Subjects were divided into groups according to their motivational disposition in terms of action orientation and individual rating of scene interest.
    • Oxidation of Dietary Amino Acids Disrupts their Anabolic Effects on Bone Marrow-Derived Mesenchymal Stem Cells

      El Refaey, Mona M.; Department of Cellular Biology and Anatomy (2016-07)
      Age-dependent bone loss has been well documented in both human and animal models. Since it has been proposed that aging is associated with an increase in the generation of damaging reactive oxygen species (ROS), our hypothesis was that the oxidized products of dietary amino acids could play a role in age-induced bone loss by altering osteoprogenitor cell differentiation and function or activating osteoclastic activity. We first examined the effects of the oxidized nutrients on the bone marrow-derived mesenchymal stem cells and our data showed a decrease in the protein and gene expression of osteogenic markers normally stimulated by nutrients. Aromatic amino acids activated signaling pathways involved in protein synthesis in vitro, and thus, in contrast, the oxidized metabolites of these aromatic amino acids had no effect on the activation of these anabolic pathways. We then examined the bone marrow concentration of the oxidized aromatic amino acids in mature (12 months) vs. aged (24 months) C57BL/6 mice and found that kynurenine, the oxidized product of the aromatic amino acid tryptophan, was found in the highest concentration in 12 months mice. Thus, we tested the effects of kynurenine, fed as a dietary supplement, on the bone mass of twelve-month-old C57BL/6 mice compared to a normal protein diet to see if the oxidized amino acid would induce a pattern consistent with age-related bone loss. Twelve-month-old, male C57BL/6 mice were fed one of four diets; 18% protein diet (normal protein diet); 8% protein diet + tryptophan; 8% protein diet + kynurenine (50 μM) and 8% protein diet + kynurenine (100 μM) for 8 wks. Bone densitometry and micro-CT analyses demonstrated bone loss following the kynurenine diet. Histological and histomorphometric studies showed a decreased bone formation and an increased MONA M. EL REFAEY Oxidation of Dietary Amino Acids Disrupts Their Anabolic Effects on Bone Marrow-Derived Mesenchymal Stem Cells (Under the direction of DR. CARLOS M. ISALES) osteoclastic activity in the kynurenine groups; these animals also exhibited an increase in serum pyridinoline, a marker of bone breakdown. Thus, these data demonstrate that feeding an oxidized product of an essential amino acid induces bone loss in a pattern consistent with accelerated aging, and we propose that one of the mechanisms involved in age-induced bone loss may be from alterations of dietary nutrients by the increased generation of ROS associated with aging.
    • Palmitoleate Induces Hepatic Steatosis but Suppresses Liver Inflammatory Response in Mice

      Guo, Xin; Li, Honggui; Xu, Hang; Halim, Vera; Zhang, Weiyu; Wang, Huan; Ong, Kuok Teong; Woo, Shih-Lung; Walzem, Rosemary L.; Mashek, Douglas G.; et al. (2012-06-29)
      The interaction between fat deposition and inflammation during obesity contributes to the development of non-alcoholic fatty liver disease (NAFLD). The present study examined the effects of palmitoleate, a monounsaturated fatty acid (16⠶1n7), on liver metabolic and inflammatory responses, and investigated the mechanisms by which palmitoleate increases hepatocyte fatty acid synthase (FAS) expression. Male wild-type C57BL/6J mice were supplemented with palmitoleate and subjected to the assays to analyze hepatic steatosis and liver inflammatory response. Additionally, mouse primary hepatocytes were treated with palmitoleate and used to analyze fat deposition, the inflammatory response, and sterol regulatory element-binding protein 1c (SREBP1c) activation. Compared with controls, palmitoleate supplementation increased the circulating levels of palmitoleate and improved systemic insulin sensitivity. Locally, hepatic fat deposition and SREBP1c and FAS expression were significantly increased in palmitoleate-supplemented mice. These pro-lipogenic events were accompanied by improvement of liver insulin signaling. In addition, palmitoleate supplementation reduced the numbers of macrophages/Kupffer cells in livers of the treated mice. Consistently, supplementation of palmitoleate decreased the phosphorylation of nuclear factor kappa B (NF-κB, p65) and the expression of proinflammatory cytokines. These results were recapitulated in primary mouse hepatocytes. In terms of regulating FAS expression, treatment of palmitoleate increased the transcription activity of SREBP1c and enhanced the binding of SREBP1c to FAS promoter. Palmitoleate also decreased the phosphorylation of NF-κB p65 and the expression of proinflammatory cytokines in cultured macrophages. Together, these results suggest that palmitoleate acts through dissociating liver inflammatory response from hepatic steatosis to play a unique role in NAFLD.