Respiratory Health Associated With Systemic Metal Exposure in Post-9/11 Veterans in the Department of Veterans Affairs Toxic Embedded Fragment Registry.

OBJECTIVE: Adverse respiratory outcomes in post-9/11 veterans with elevated urinary metal measures and enrolled in the VA's Toxic Embedded Fragment registry were compared to those without elevated urinary metals. METHODS: Veterans completed questionnaires, underwent pulmonary physiology tests (pulmonary function and oscillometry), and provided urine samples for analysis of 13 metals. Respiratory symptoms, diagnoses, and physiology measures were compared in veterans with ≥1 urine metal elevation to those without metal elevations, adjusted for covariates, including smoking. RESULTS: Among 402 study participants, 24% had elevated urine metals, often just exceeding upper limits of reference values. Compared to veterans without elevated metals, those with elevated metals had had higher FEV 1 values but similar frequencies of respiratory symptoms and diagnoses and abnormalities on pulmonary physiology tests. CONCLUSIONS: Mild systemic metal elevations in post-9/11 veterans are not associated with adverse respiratory health outcomes.

Implementation of low-dose CT screening in two different health care systems: Mount Sinai Healthcare System and Phoenix VA Health Care System.

Implementation of lung screening (LS) programs is challenging even among health care organizations that have the motivation, the resources, and more importantly, the goal of providing for life-saving early detection, diagnosis, and treatment of lung cancer. We provide a case study of LS implementation in different healthcare systems, at the Mount Sinai Healthcare System (MSHS) in New York City, and at the Phoenix Veterans Affairs Health Care System (PVAHCS) in Phoenix, Arizona. This will illustrate the commonalities and differences of the LS implementation process in two very different health care systems in very different parts of the United States. Underlying the successful implementation of these LS programs was the use of a comprehensive management system, the Early Lung Cancer Action Program (ELCAP) Management SystemTM. The collaboration between MSHS and PVAHCS over the past decade led to the ELCAP Management SystemTM being gifted by the Early Diagnosis and Treatment Research Foundation to the PVAHCS, to develop a "VA-ELCAP" version. While there remain challenges and opportunities to continue improving LS and its implementation, there is an increasing realization that most patients who are diagnosed with lung cancer as a result of annual LS can be cured, and that of all the possible risks associated with LS, the greater risk of all is for heavy cigarette smokers not to be screened. We identified 10 critical components in implementing a LS program. We provided the details of each of these components for the two healthcare systems. Most importantly, is that continual re-evaluation of the screening program is needed based on the ongoing quality assurance program and database of the actual screenings. At minimum, there should be an annual review and updating. As early diagnosis of lung cancer must be followed by optimal treatment to be effective, treatment advances for small, early lung cancers diagnosed as a result of screening also need to be assessed and incorporated into the entire screening and treatment program.

Diffuse traumatic brain injury affects chronic corticosterone function in the rat.

As many as 20-55% of patients with a history of traumatic brain injury (TBI) experience chronic endocrine dysfunction, leading to impaired quality of life, impaired rehabilitation efforts and lowered life expectancy. Endocrine dysfunction after TBI is thought to result from acceleration-deceleration forces to the brain within the skull, creating enduring hypothalamic and pituitary neuropathology, and subsequent hypothalamic-pituitary endocrine (HPE) dysfunction. These experiments were designed to test the hypothesis that a single diffuse TBI results in chronic dysfunction of corticosterone (CORT), a glucocorticoid released in response to stress and testosterone. We used a rodent model of diffuse TBI induced by midline fluid percussion injury (mFPI). At 2months postinjury compared with uninjured control animals, circulating levels of CORT were evaluated at rest, under restraint stress and in response to dexamethasone, a synthetic glucocorticoid commonly used to test HPE axis regulation. Testosterone was evaluated at rest. Further, we assessed changes in injury-induced neuron morphology (Golgi stain), neuropathology (silver stain) and activated astrocytes (GFAP) in the paraventricular nucleus (PVN) of the hypothalamus. Resting plasma CORT levels were decreased at 2months postinjury and there was a blunted CORT increase in response to restraint induced stress. No changes in testosterone were measured. These changes in CORT were observed concomitantly with altered complexity of neuron processes in the PVN over time, devoid of neuropathology or astrocytosis. Results provide evidence that a single moderate diffuse TBI leads to changes in CORT function, which can contribute to the persistence of symptoms related to endocrine dysfunction. Future experiments aim to evaluate additional HP-related hormones and endocrine circuit pathology following diffuse TBI.

Comparison and evaluation of dietary quality between older and younger Mexican-American women.

OBJECTIVE: To compare and evaluate the dietary quality of young and older sedentary Mexican-American women. Understanding key dietary concerns, while considering developmental transition periods and cultural relevance, can provide insight for developing appropriate nutrition interventions. DESIGN: Cross-sectional dietary data were collected using unannounced 24 h diet recalls to assess nutrient intake adequacy (Estimated Average Requirement cut-point method) and dietary quality (Healthy Eating Index (HEI) 2010). SETTING: Mujeres en Acción and Madres para la Salud, two community-based physical activity interventions. SUBJECTS: Participants were 139 young (28 (sd 6) years) and 124 older (55 (sd 7) years) overweight/obese sedentary Mexican-American women (BMI=25·0-35·0 kg/m2) of low socio-economic status. RESULTS: Older women consumed less Ca, Fe, folate, empty calories and energy from carbohydrate, but more fruit, vegetables, greens and beans, and fibre than younger women (all P<0·05). Over 60 % of all participants had an intake below recommendations for fibre, Ca, vitamin E, vitamin C and folate. Both groups had low total HEI-2010 scores (62 for older and 63 for younger women; NS), with 57 % of older and 48 % of younger women classified as having a poor diet. CONCLUSIONS: Despite differences in nutrient requirements according to developmental transition periods (childbearing v. perimenopausal), overall, older and younger Mexican-American women generally had low-quality diets and may benefit from dietary quality improvement.

Participation in a Social-Support Physical Activity Intervention Modestly Improves Lipoprotein Cholesterol Distribution Among Postpartum Sedentary Hispanic Women.

BACKGROUND: The effects of moderate intensity walking on lipoprotein remodeling in postpartum Hispanic women are unknown. METHODS: Sedentary postpartum Hispanic women (28.2 ± 5.6 y; BMI = 29.3 ± 3.3 kg/m2) participating in a social support physical activity (PA) intervention, were randomly assigned to a 12-month walking program (walkers; n = 22; target 150 min/wk, moderate intensity) or a control group (nonwalkers; n = 22). Fasting lipids and cholesterol distribution within low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles were measured at baseline (BL), 6 months, and 12 months. RESULTS: Walkers had an 11% increase and nonwalkers a 7% decrease in HDL cholesterol from 6 to 12 months (P = .0367) without an effect on LDL cholesterol. Whereas nonwalkers had virtually no change in mean LDL particle size, walkers had a borderline reduction in LDL size from BL (268.7 ± 4.1 Å) to 6 months (266.9 ± 4.9 Å), followed by a significant increase in size by 12 months (269.7 ± 4.1 Å; P = .011). The proportion of cholesterol in large LDL particles decreased by 15% from BL to 6 months, but subsequently increased 25% by 12 months among walkers; changes among nonwalkers were smaller and in opposite direction (4% and -3%, respectively; P = .0004). CONCLUSIONS: Participation in the social-support PA intervention resulted in slightly increased HDL cholesterol concentrations and a modest and beneficial shift toward larger, less atherogenic LDL particles.

Correlates of depressive symptoms after birth for Latinas who are overweight or obese.

Depression symptoms and overweight/obesity are common concerns during childbearing. Both conditions are associated with poor outcomes at birth and can have long-lasting consequences. Predictors of depressive symptoms among overweight and obese low-income and ethnically diverse women are not known. Data are from the Madres para la Salud trial with 139 postpartum Latinas. Depressive symptoms during a prior pregnancy were positively related, while social support and moderate intensity physical activity (PA) were negatively related to depressive symptoms after birth. Social support and PA may be effective interventions, particularly for women who have experienced depressive symptoms in a prior pregnancy.

A comparison of a social support physical activity intervention in weight management among post-partum Latinas.

BACKGROUND: Weight gain during the childbearing years and failure to lose pregnancy weight after birth contribute to the development of obesity in postpartum Latinas. METHODS: Madres para la Salud [Mothers for Health] was a 12-month, randomized controlled trial exploring a social support intervention with moderate-intensity physical activity (PA) seeking to effect changes in body fat, fat tissue inflammation, and depression symptoms in sedentary postpartum Latinas. This report describes the efficacy of the Madres intervention. RESULTS: The results show that while social support increased during the active intervention delivery, it declined to pre-intervention levels by the end of the intervention. There were significant achievements in aerobic and total steps across the 12 months of the intervention, and declines in body adiposity assessed with bioelectric impedance. CONCLUSIONS: Social support from family and friends mediated increases in aerobic PA resulting in decrease in percent body fat. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01908959.

Social marketing: approach to cultural and contextual relevance in a community-based physical activity intervention.

We report the social marketing strategies used for the design, recruitment and retention of participants in a community-based physical activity (PA) intervention, Madres para la Salud (Mothers for Health). The study example used to illustrate the use of social marketing is a 48-week prescribed walking program, Madres para la Salud (Mothers for Health), which tests a social support intervention to explore the effectiveness of a culturally specific program using 'bouts' of PA to effect the changes in body fat, fat tissue inflammation and postpartum depression symptoms in sedentary Hispanic women. Using the guidelines from the National Benchmark Criteria, we developed intervention, recruitment and retention strategies that reflect efforts to draw on community values, traditions and customs in intervention design, through partnership with community members. Most of the women enrolled in Madres para la Salud were born in Mexico, largely never or unemployed and resided among the highest crime neighborhoods with poor access to resources. We developed recruitment and retention strategies that characterized social marketing strategies that employed a culturally relevant, consumer driven and problem-specific design. Cost and benefit of program participation, consumer-derived motivation and segmentation strategies considered the development transition of the young Latinas as well as cultural and neighborhood barriers that impacted retention are described.

Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity.

Elevated blood branched-chain amino acids (BCAA) are often associated with insulin resistance and type 2 diabetes, which might result from a reduced cellular utilization and/or incomplete BCAA oxidation. White adipose tissue (WAT) has become appreciated as a potential player in whole body BCAA metabolism. We tested if expression of the mitochondrial BCAA oxidation checkpoint, branched-chain α-ketoacid dehydrogenase (BCKD) complex, is reduced in obese WAT and regulated by metabolic signals. WAT BCKD protein (E1α subunit) was significantly reduced by 35-50% in various obesity models (fa/fa rats, db/db mice, diet-induced obese mice), and BCKD component transcripts significantly lower in subcutaneous (SC) adipocytes from obese vs. lean Pima Indians. Treatment of 3T3-L1 adipocytes or mice with peroxisome proliferator-activated receptor-γ agonists increased WAT BCAA catabolism enzyme mRNAs, whereas the nonmetabolizable glucose analog 2-deoxy-d-glucose had the opposite effect. The results support the hypothesis that suboptimal insulin action and/or perturbed metabolic signals in WAT, as would be seen with insulin resistance/type 2 diabetes, could impair WAT BCAA utilization. However, cross-tissue flux studies comparing lean vs. insulin-sensitive or insulin-resistant obese subjects revealed an unexpected negligible uptake of BCAA from human abdominal SC WAT. This suggests that SC WAT may not be an important contributor to blood BCAA phenotypes associated with insulin resistance in the overnight-fasted state. mRNA abundances for BCAA catabolic enzymes were markedly reduced in omental (but not SC) WAT of obese persons with metabolic syndrome compared with weight-matched healthy obese subjects, raising the possibility that visceral WAT contributes to the BCAA metabolic phenotype of metabolically compromised individuals.

Overweight, obesity, and neighborhood characteristics among postpartum Latinas.

BACKGROUND: Weight gain during the childbearing years and failure to lose pregnancy weight after birth contribute to the development of obesity in Latinas. DESIGN AND METHODS: Madres para la Salud (Mothers for Health) is a 12-month prospective, randomized controlled trial exploring a social support intervention with moderate-intensity physical activity to effect changes in body fat, systemic and fat tissue inflammation, and depression symptoms in sedentary postpartum Latinas. This paper describes the initial body composition of the sample, social support, and neighborhood contextual correlations of overweight and obese Latina mothers within the first 6 months after birth. RESULTS: The mean body mass index was 29.68 with 38.56% bioelectrical impedence analysis for body fat. Elements of the environment (e.g., opportunities to walk) received middle or high scores. Access to healthy food was positively related to favorability of the walking environment. Waist-to-hip ratio was uncorrelated with other obesity-related indices. CONCLUSIONS: The body adiposity of these Latina mothers was coupled with low levels of social support from family and friends and neighborhood characteristics that were unfavorable to walking.

Physical activity and sedentary behaviors in postpartum Latinas: Madres para la Salud.

PURPOSE: To describe the physical activity (PA) and sedentary behaviors of postpartum Latinas who are overweight or obese before initiating Madres para la Salud, a social support-mediated walking intervention to promote postpartum weight loss. METHODS: One hundred thirty-nine postpartum women (13.6 ± 7.7 wk since childbirth, age = 28.3 ± 5.6 yr, BMI = 29.7 ± 3.5 kg · m(-2); mean ± SD), recruited from organizations serving Latino residents in the Phoenix, Arizona, area completed the Stanford Brief Activity Survey and concurrently wore an accelerometer (ActiGraph) and a pedometer for 7 d and kept a PA record. RESULTS: Most were classified as inactive and lightly active on the Stanford Brief Activity Survey (51% inactive, 37% light, 11% moderate). Most time was spent in sedentary (512.0 ± 169.9 min · d(-1)) and light-intensity PA (242.4 ± 51.4 min · d(-1)) with less time in moderate-intensity lifestyle (78.3 ± 39.9 min · d(-1)), moderate-intensity walking (16.6 ± 14.4 min · d(-1)), and vigorous-intensity PA (0.34 ± 1.5 min · d(-1)). Pedometer steps per day were low (total = 4973 ± 2202 steps, aerobic = 412 ± 774 steps), with most participants rated as sedentary (61%) or low active (28.1%). Consistent with objective PA measures, PA records showed more time spent in light-intensity PA such as home care, cooking, child care and self-care tasks, occupation, religious events, and watching television. CONCLUSION: By and large, the postpartum Latinas enrolled spent most of their day in low-intensity activity levels with little time spent in health-enhancing PA levels/behaviors. This demographic should be the focus of PA interventions to increase PA to health-enhancing levels.

Promotoras' roles in integrative validity and treatment fidelity efforts in randomized controlled trials.

Promotoras from the communities in which interventions are implemented can be effective contributors to validity and fidelity efforts. This article describes a 48-week randomized controlled trial Madres para la Salud (Mothers for Health) and illustrates the use of promotoras as collaborative members of the research team to contribute to attaining integrative validity and treatment fidelity. Madres para la Salud implements a culturally tailored physical activity program to effect changes in body fat, systemic and fat tissue inflammation, and depression symptoms. The significance of Madres para la Salud treatment validity and fidelity processes includes cultural tailoring of a social support intervention, and a promotora model to incorporate initial and ongoing fidelity monitoring.

Instrument selection for randomized controlled trials: why this and not that?

A fundamental linchpin for obtaining rigorous findings in quantitative research involves the selection of survey instruments. Psychometric recommendations are available for the processes for scale development and testing and guidance for selection of established scales. These processes are necessary to address the validity link between the phenomena under investigation, the empirical measures and, ultimately, the theoretical ties between these and the world views of the participants. Detailed information is most often provided about study design and protocols, but far less frequently is a detailed theoretical explanation provided for why specific instruments are chosen. Guidance to inform choices is often difficult to find when scales are needed for specific cultural, ethnic, or racial groups. This paper details the rationale underlying instrument selection for measurement of the major processes (intervention, mediator and moderator variables, outcome variables) in an ongoing study of postpartum Latinas, Madres para la Salud [Mothers for Health]. The rationale underpinning our choices includes a discussion of alternatives, when appropriate. These exemplars may provide direction for other intervention researchers who are working with specific cultural, racial, or ethnic groups or for other investigators who are seeking to select the 'best' instrument. Thoughtful consideration of measurement and articulation of the rationale underlying our choices facilitates the maintenance of rigor within the study design and improves our ability to assess study outcomes.

Madres para la Salud: design of a theory-based intervention for postpartum Latinas.

BACKGROUND: Weight gain in young women suggests that childbearing may be an important contributor to the development of obesity in women. Depressive symptoms can interfere with resumption of normal activity levels following childbirth or with the initiation of or adherence to physical activity programs essential for losing pregnancy weight. Depression symptoms may function directly to promote weight gain through a physiologic mechanism. Obesity and its related insulin resistance may contribute to depressed mood physiologically. Although physical activity has well-established beneficial effects on weight management and depression, women tend to under participate in physical activity during childbearing years. Further, the mechanisms underpinning the interplay of overweight, obesity, physical activity, depression, and inflammatory processes are not clearly explained. OBJECTIVES: This report describes the theoretical rationale, design considerations, and cultural relevance for "Madres para la Salud" [Mothers for Health]. DESIGN AND METHODS: Madres para la Salud is a 12 month prospective, randomized controlled trial exploring the effectiveness of a culturally specific intervention using "bouts" of physical activity to effect changes in body fat, systemic and fat tissue inflammation, and postpartum depression symptoms in sedentary postpartum Latinas. SUMMARY: The significance and innovation of Madres para la Salud includes use of a theory-driven approach to intervention, specification and cultural relevance of a social support intervention, use of a Promotora model to incorporate cultural approaches, use of objective measures of physical activity in post partum Latinas women, and the examination of biomarkers indicative of cardiovascular risk related to physical activity behaviors in postpartum Latinas.

Insulin metabolism in human adipocytes from subcutaneous and visceral depots.

Subjects with the metabolic syndrome (insulin resistance, glucose intolerance, dyslipidemia, hypertension, etc.) have a relative increase in abdominal fat tissue compared to normal individuals and obesity has also been shown to be associated with a decrease in insulin clearance. The majority of the clearance of insulin is due to the action of insulin-degrading enzyme (IDE) and IDE is present throughout all tissues. Since abdominal fat is increased in obesity we hypothesized that IDE may be altered in the different fat depots. Adipocytes were isolated from fat samples obtained from subjects during elective abdominal surgery. Fat samples were taken from subcutaneous (SQ) and visceral (VIS) sites. Insulin metabolism was compared in adipocytes isolated from SQ and VIS fat tissue. Adipocytes from the VIS site degraded more insulin that those from SQ fat tissue. Inhibitors of cathepsins B and D has no effect on the degradation of insulin, while bacitracin, an inhibitor of IDE, inhibited degradation by approx. 33% in both SQ and VIS adipocytes. These data show that insulin metabolism is relatively greater in VIS than in SQ fat tissue and potentially due to IDE.

Pioglitazone reduces inflammatory responses of human adipocytes to factors secreted by monocytes/macrophages.

Infiltration of monocyte-derived macrophages into adipose tissue may contribute to tissue and systemic inflammation and insulin resistance. We hypothesized that pioglitazone (Pio) could specifically reduce the inflammatory response of adipocytes to factors released by monocytes/macrophages. We show that macrophage factors (Mphi-factors) greatly increase expression levels of proinflammatory adipokines, chemokines, and adhesion molecules in human subcutaneous and visceral adipose tissue (SAT and VAT) as well as in adipocytes (up to several hundredfold of control). Compared with SAT, VAT showed enhanced basal and Mphi-factor-induced inflammatory responses. Mphi-factors also induced greater lipolysis in adipocytes, as assessed by concentrations of glycerol released from the cells (196 +/- 13 vs. 56 +/- 7 microM in control, P < 0.05). Pretreatment of adipose tissue or adipocytes with Pio reduced these responses to Mphi-factors (by 13-86%, P < 0.05) and prevented Mphi-factor suppression of adiponectin expression. Furthermore, Pio pretreatment of adipocytes and macrophages tended to further reduce inflammatory responses of adipocytes to Mphi-factors and monocyte adhesion to Mphi-factor-activated adipocytes. In support of these in vitro data, media conditioned by monocytes isolated from impaired glucose-tolerant subjects treated with Pio (compared with placebo) induced release of lower concentrations of proinflammatory adipokines and glycerol (100 +/- 7 vs. 150 +/- 15 microM, P < 0.05) from adipocytes. In summary, Pio decreases inflammatory responses in adipose tissue/cells induced by monocytes/macrophages by acting on either or both cell types. These beneficial effects of Pio may attenuate proinflammatory responses resulting from monocyte/macrophage infiltration into adipose tissue and suppress tissue inflammation resulting from the interaction between both cell types.

Pioglitazone inhibits the expression of inflammatory cytokines from both monocytes and lymphocytes in patients with impaired glucose tolerance.

OBJECTIVE: The current study determines whether pioglitazone (PIO) therapy reduces both monocyte and lymphocyte inflammatory activity and their ability to induce inflammation in other tissues. METHODS AND RESULTS: Monocyte and lymphocyte cytokine gene and protein expression of interleukin (IL)-6 were first shown to be greater in subjects with impaired glucose tolerance (IGT) than in subjects with normal glucose tolerance. Sixty-six IGT subjects were then randomized to 4,5 months of placebo or PIO therapy. After receiving PIO, subjects had lower triglycerides and higher HDL cholesterol (P<0.05) than did subjects receiving placebo. Monocyte gene and protein expression of IL-1 beta, IL-6, and IL-8 (and IL-2, IL-6 and IL-8 from lymphocytes) was significantly lower after PIO therapy in the resting state, as well as after lipopolysaccharide (LPS) stimulation (P<0.05 for all). Moreover, IL-6, IL-8, and MCP-1 gene expression were decreased by nearly 50% in human adipocytes exposed to conditioned media from monocytes or lymphocytes from PIO treated subjects. CONCLUSIONS: These results demonstrate that PIO therapy in IGT can reduce proinflammatory gene and protein expression from both monocytes and lymphocytes. This intervention also reduces the inflammatory cross-talk between these immune cells and adipose tissue, which could in turn contribute to the metabolic improvements resulting from PIO therapy.

Application of DNA microarray to the study of human adipose tissue/cells.

Adipose tissue is increasingly recognized as a metabolically active endocrine organ with multiple functions beyond its lipid storage capability. Various constituents of the tissue, such as mature adipocytes and stromal vascular cells, have distinct functions. For example, they express and secrete different kinds of bioactive molecules collectively called adipokines. Altered adipokine secretion patterns characterize obesity and insulin resistance, which are major risk factors for type 2 diabetes mellitus. The contribution of dysregulated adipokine expression to these diseases may be assembled from transcriptomic profiles of the tissue and/or its cellular constituents. The gene expression profiles may also complement genetic approaches to identify disease susceptibility genes. Here, we describe an application of gene expression profiling using DNA microarrays to study human adipose tissue, adipocytes, and stromal vascular cells.

Overweight and obesity in postpartum Hispanic women.

Overweight and obesity vary in prevalence among particular groups, and are especially problematic for childbearing Hispanic women. The complex interaction between physical changes associated with pregnancy, role changes accompanying birth, and family and cultural values related to childbearing are superimposed upon the underlying mechanisms that create or perpetuate obesity. In this article we review biological and behavioral research on obesity in postpartum Hispanic women to identify critical components for intervention studies focused on weight management. Recommendations are offered for health care providers and researchers.

Amyloid precursor protein expression is upregulated in adipocytes in obesity.

The aim of this study was to determine whether amyloid precursor protein (APP) is expressed in human adipose tissue, dysregulated in obesity, and related to insulin resistance and inflammation. APP expression was examined by microarray expression profiling of subcutaneous abdominal adipocytes (SAC) and cultured preadipocytes from obese and nonobese subjects. Quantitative real-time PCR (QPCR) was performed to confirm differences in APP expression in SAC and to compare APP expression levels in adipose tissue, adipocytes, and stromal vascular cells (SVCs) from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) specimens. Adipose tissue samples were also examined by western blot and immunofluorescence confocal microscopy. Microarray studies demonstrated that APP mRNA expression levels were higher in SAC (approximately 2.5-fold) and preadipocytes (approximately 1.4) from obese subjects. Real-time PCR confirmed increased APP expression in SAC in a separate group of obese compared with nonobese subjects (P=0.02). APP expression correlated to in vivo indices of insulin resistance independently of BMI and with the expression of proinflammatory genes, such as monocyte chemoattractant protein-1 (MCP-1) (R=0.62, P=0.004), macrophage inflammatory protein-1alpha (MIP-1alpha) (R=0.60, P=0.005), and interleukin-6 (IL-6) (R=0.71, P=0.0005). Full-length APP protein was detected in adipocytes by western blotting and APP and its cleavage peptides, Abeta40 and Abeta42, were observed in SAT and VAT by immunofluorescence confocal microscopy. In summary, APP is highly expressed in adipose tissue, upregulated in obesity, and expression levels correlate with insulin resistance and adipocyte cytokine expression levels. These data suggest a possible role for APP and/or Abeta in the development of obesity-related insulin resistance and adipose tissue inflammation.