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What have we really learned about macrophage recruitment to adipose tissue?
Hasty AH, Gutierrez DA
(2014) Endocrinology 155: 12-4
MeSH Terms: Adipose Tissue, Animals, Bone Marrow, Gene Expression Regulation, Leptin, Male, Receptors, Leptin
Added May 20, 2014
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7 MeSH Terms
Glycemic load is associated with oxidative stress among prevalent maintenance hemodialysis patients.
Limkunakul C, Sundell MB, Pouliot B, Graves AJ, Shintani A, Ikizler TA
(2014) Nephrol Dial Transplant 29: 1047-53
MeSH Terms: Absorptiometry, Photon, Adiponectin, Adult, Biomarkers, Blood Glucose, Cross-Sectional Studies, Diet, Female, Glycemic Index, Humans, Inflammation, Leptin, Male, Middle Aged, Oxidative Stress, Renal Dialysis, Retrospective Studies
Show Abstract · Added September 29, 2014
BACKGROUND - High glycemic index (GI) and glycemic load (GL) are associated with increased levels of oxidative stress and systemic inflammation in the general population. Maintenance hemodialysis (MHD) patients are known to have excessive oxidative stress burden and inflammation. In this study, we examined the relationship between dietary GI or GL and markers of oxidative stress or inflammation among prevalent MHD patients.
METHODS - A registered dietitian obtained GI, GL and other dietary data from 58 MHD patients. Two separate 24-h diet recalls (a hemodialysis day and a non-hemodialysis day) were analyzed using the Nutrition Data System for Research (NDS-R) software. Plasma or serum concentrations of F2-isoprostanes, high sensitivity C-reactive protein (hsCRP), leptin and adiponectin (ADPN) were measured in fasting state. Fat mass was measured by dual-energy X-ray absorptiometry (DEXA). Cross-sectional associations between GI, GL and markers of interest were examined by multiple regression analysis with adjustment for potential covariates.
RESULTS - Mean (±SD) age, body mass index (BMI) and total trunk fat were 47 ± 12 years, 29.5 ± 6.8 kg/m(2) and 16.4 ± 8.8 kg, respectively. Dietary GI was associated with trunk fat (r = -0.182, P = 0.05) but not with F2-isoprostanes and hsCRP. In contrast, GL was significantly associated with F2-isoprostanes (P = 0.002), in unadjusted analysis, which remained in adjusted analyses, adjusting for age and sex (P = 0.005), and after adjusting for BMI, trunk fat and waist/hip ratio (P = 0.004). Addition of leptin or ADPN did not alter the significance of the association. GL also correlated with hsCRP (P = 0.03), but this association was modified by BMI and trunk fat.
CONCLUSIONS - Dietary GL is significantly associated with markers of oxidative stress and inflammation among prevalent MHD patients, independent of the body composition and adipocytokines. These data indicate the importance of the contents of dietary nutrient intake composition and its potential role in determining the metabolic disturbances in MHD patients.
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17 MeSH Terms
Impact of hematopoietic cyclooxygenase-1 deficiency on obesity-linked adipose tissue inflammation and metabolic disorders in mice.
Saraswathi V, Ramnanan CJ, Wilks AW, Desouza CV, Eller AA, Murali G, Ramalingam R, Milne GL, Coate KC, Edgerton DS
(2013) Metabolism 62: 1673-85
MeSH Terms: Adiponectin, Adipose Tissue, Animals, Biomarkers, Blotting, Western, Bone Marrow Cells, Bone Marrow Transplantation, Cyclooxygenase 1, Diet, High-Fat, Eating, Female, Fluorescent Antibody Technique, Inflammation, Kidney, Leptin, Liver, Macrophages, Mice, Mice, Knockout, Obesity, Real-Time Polymerase Chain Reaction, Weight Gain
Show Abstract · Added March 26, 2014
OBJECTIVE - Adipose tissue (AT)-specific inflammation is considered to mediate the pathological consequences of obesity and macrophages are known to activate inflammatory pathways in obese AT. Because cyclooxygenases play a central role in regulating the inflammatory processes, we sought to determine the role of hematopoietic cyclooxygenase-1 (COX-1) in modulating AT inflammation in obesity.
MATERIALS/METHODS - Bone marrow transplantation was performed to delete COX-1 in hematopoietic cells. Briefly, female wild type (wt) mice were lethally irradiated and injected with bone marrow (BM) cells collected from wild type (COX-1+/+) or COX-1 knock-out (COX-1-/-) donor mice. The mice were fed a high fat diet for 16 weeks.
RESULTS - The mice that received COX-1-/- bone marrow (BM-COX-1-/-) exhibited a significant increase in fasting glucose, total cholesterol and triglycerides in the circulation compared to control (BM-COX-1+/+) mice. Markers of AT-inflammation were increased and were associated with increased leptin and decreased adiponectin in plasma. Hepatic inflammation was reduced with a concomitant reduction in TXB2 levels. The hepatic mRNA expression of genes involved in lipogenesis and lipid transport was increased while expression of genes involved in regulating hepatic glucose output was reduced in BM-COX-1-/- mice. Finally, renal inflammation and markers of renal glucose release were increased in BM-COX-1-/- mice.
CONCLUSION - Hematopoietic COX-1 deletion results in impairments in metabolic homeostasis which may be partly due to increased AT inflammation and dysregulated adipokine profile. An increase in renal glucose release and hepatic lipogenesis/lipid transport may also play a role, at least in part, in mediating hyperglycemia and dyslipidemia, respectively.
Published by Elsevier Inc.
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22 MeSH Terms
Adipose tissue density, a novel biomarker predicting mortality risk in older adults.
Murphy RA, Register TC, Shively CA, Carr JJ, Ge Y, Heilbrun ME, Cummings SR, Koster A, Nevitt MC, Satterfield S, Tylvasky FA, Strotmeyer ES, Newman AB, Simonsick EM, Scherzinger A, Goodpaster BH, Launer LJ, Eiriksdottir G, Sigurdsson S, Sigurdsson G, Gudnason V, Lang TF, Kritchevsky SB, Harris TB
(2014) J Gerontol A Biol Sci Med Sci 69: 109-17
MeSH Terms: Absorptiometry, Photon, Adiponectin, Adipose Tissue, Aged, Aged, 80 and over, Aging, Animals, Biomarkers, Body Mass Index, Female, Follow-Up Studies, Humans, Leptin, Macaca fascicularis, Male, Obesity, Prognosis, Prospective Studies, Risk Factors, Survival Rate
Show Abstract · Added February 28, 2014
BACKGROUND - Knowledge of adipose composition in relation to mortality may help delineate inconsistent relationships between obesity and mortality in old age. We evaluated relationships between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density, mortality, biomarkers, and characteristics.
METHODS - VAT and SAT density were determined from computed tomography scans in persons aged 65 and older, Health ABC (n = 2,735) and AGES-Reykjavik (n = 5,131), and 24 nonhuman primates (NHPs). Associations between adipose density and mortality (4-13 years follow-up) were assessed with Cox proportional hazards models. In NHPs, adipose density was related to serum markers and tissue characteristics.
RESULTS - Higher density adipose tissue was associated with mortality in both studies with adjustment for risk factors including adipose area, total fat, and body mass index. In women, hazard ratio and 95% CI for the densest quintile (Q5) versus least dense (Q1) for VAT density were 1.95 (1.36-2.80; Health ABC) and 1.88 (1.31-2.69; AGES-Reykjavik) and for SAT density, 1.76 (1.35-2.28; Health ABC) and 1.56 (1.15-2.11; AGES-Reykjavik). In men, VAT density was associated with mortality in Health ABC, 1.52 (1.12-2.08), whereas SAT density was associated with mortality in both Health ABC, 1.58 (1.21-2.07), and AGES-Reykjavik, 1.43 (1.07-1.91). Higher density adipose tissue was associated with smaller adipocytes in NHPs. There were no consistent associations with inflammation in any group. Higher density adipose tissue was associated with lower serum leptin in Health ABC and NHPs, lower leptin mRNA expression in NHPs, and higher serum adiponectin in Health ABC and NHPs.
CONCLUSION - VAT and SAT density provide a unique marker of mortality risk that does not appear to be inflammation related.
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20 MeSH Terms
Obesity and insulin resistance in pediatric acute lymphoblastic leukemia worsens during maintenance therapy.
Esbenshade AJ, Simmons JH, Koyama T, Lindell RB, Friedman DL
(2013) Pediatr Blood Cancer 60: 1287-91
MeSH Terms: Adolescent, Adult, Blood Glucose, Body Mass Index, Child, Child, Preschool, Fasting, Female, Follow-Up Studies, Humans, Insulin, Insulin Resistance, Leptin, Male, Obesity, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prospective Studies, Triglycerides
Show Abstract · Added March 7, 2014
BACKGROUND - Pediatric acute lymphoblastic leukemia (ALL) survivors are at increased risk for the metabolic syndrome (MS). To establish the trajectory of development during active treatment, we followed patients longitudinally over the first year of maintenance therapy.
PROCEDURE - In a prospective cohort of 34 pediatric ALL patients, followed over the first 12 months of ALL maintenance, we evaluated changes in body mass index (BMI), blood pressure, fasting insulin and glucose, lipids, Homeostatic Metabolic Assessment (HOMA), leptin, and adiponectin.
RESULTS - Over the study time period, the median BMI z-score increased from 0.29 to 0.66 (P = 0.001), median fasting insulin levels increased from 2.9 to 3.1 µU/ml (P = 0.023), and the proportion of patients with insulin resistance by HOMA (>3.15) increased from 3% to 24% (P = 0.016). Median leptin increased from 2.5 to 3.5 ng/ml (P = 0.001), with levels correlated with BMI z-score. Median adiponectin level decreased from 18.0 to 14.0 µg/ml (P = 0.009), with levels inversely correlated to BMI z-score. No change in median total cholesterol and LDL levels was observed. Median triglycerides decreased (P < 0.001) and there was a trend to increase in HDL (P = 0.058). Blood pressure did not significantly change, although overall prevalence of systolic and diastolic hypertension was high (23.5% and 26.4%, respectively).
CONCLUSIONS - Following patients over the first year of ALL maintenance therapy demonstrated that components of the MS significantly worsen over time. Preventive interventions limiting increases in BMI and insulin resistance during maintenance therapy should be targeted during this time period to avoid long-term morbidity associated with the MS in long-term survivors.
Copyright © 2013 Wiley Periodicals, Inc.
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18 MeSH Terms
Molecular pathways: adiponectin and leptin signaling in cancer.
Vansaun MN
(2013) Clin Cancer Res 19: 1926-32
MeSH Terms: Adiponectin, Humans, Leptin, Models, Biological, Neoplasms, Receptors, Adiponectin, Receptors, Leptin, Signal Transduction
Show Abstract · Added May 9, 2014
The increasing percentage of obese individuals in the population and its independent association of increased risk for the development of cancer have heightened the necessity to understand the molecular mechanisms that underlie this connection. The deregulation of adipokines in the setting of obesity and their impact on cancer progression and metastasis is one such area of research. Adipokines are bioactive proteins that mediate metabolism, inflammation, angiogenesis, and proliferation. Altered levels of adipokines or their cognate receptors in cancers can ultimately lead to an imbalance in downstream molecular pathways. Discovery of adipokine receptors in various cancers has highlighted the potential for novel therapeutic targets. Leptin and adiponectin represent two adipokines that elicit generally opposing molecular effects. Epidemiologic studies have highlighted associations between increased serum leptin levels and increased tumor growth, whereas adiponectin exhibits an inverse correlation with cancer development. This review addresses the current level of understanding of molecular pathways activated by adiponectin and leptin to identify the areas of intervention and facilitate advancement in the field.
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8 MeSH Terms
The relationship of oxidative stress, adiposity and metabolic risk factors in healthy Black and White American youth.
Warolin J, Coenen KR, Kantor JL, Whitaker LE, Wang L, Acra SA, Roberts LJ, Buchowski MS
(2014) Pediatr Obes 9: 43-52
MeSH Terms: Adiponectin, Adiposity, Adolescent, African Americans, Blood Glucose, Blood Pressure, Child, European Continental Ancestry Group, F2-Isoprostanes, Female, Humans, Leptin, Male, Metabolic Syndrome, Molecular Sequence Data, Oxidative Stress, Risk Factors, Triglycerides, United States
Show Abstract · Added December 10, 2013
UNLABELLED - What is already known about this subject African Americans are disproportionately affected by obesity and other metabolic risk factors in comparison to White Americans. Increasing prevalence of obesity has been associated with concomitant increases in childhood hypertension, dyslipidaemia and type 2 diabetes. Oxidative stress is associated with obesity in both adults and children. What this study adds Oxidative stress is positively associated with total body fat and truncal fat, but not with body mass index (BMI) or BMI z-score in healthy youth. Oxidative stress is associated with diastolic blood pressure in African American but not in White American healthy youth.
BACKGROUND - Oxidative stress is elevated in obese youth, but less is known regarding racial disparities in the relationship of oxidative stress with metabolic risk factors.
OBJECTIVES - To determine the relationship between oxidative stress and metabolic risk factors, adiposity, leptin, adiponectin and cardiovascular fitness (VO2PEAK ) in healthy African American and White American youth.
METHODS - A marker of oxidative stress (F2 -isoprostane), validated markers of metabolic risk factors, fitness and body composition were measured in African American (n = 82) and White American (n = 76) youth (8-17 years old) recruited over a range of BMI percentiles (4th to 99th).
RESULTS - F2 -isoprostane concentration was positively correlated with percentage body fat (r = 0.198) and percentage truncal fat (r = 0.173), but was not different between African American and White American males and females (P = 0.208). African American youth had significantly higher mean systolic and diastolic blood pressure (P = 0.023 and P = 0.011, respectively), body weight, BMI percentile and Tanner stage. After adjusting for gender, age, BMI and Tanner stage, African American youth varied from White Americans in the association of F2 -isoprostane with diastolic blood pressure (P = 0.047), but not with systolic blood pressure, triglycerides, VO2PEAK or homeostatic model assessment for insulin resistance (all P > 0.05).
CONCLUSIONS - Oxidative stress, as measured by urinary F2 -isoprostane concentrations, was positively associated with percent body fat and truncal fat in youth. Oxidative stress levels were similar among African American and White American youth. Among markers of the metabolic syndrome, a significant difference between African American and White American youth was demonstrated only in the association of oxidative stress with diastolic blood pressure.
© 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.
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19 MeSH Terms
Diabetes in Zucker diabetic fatty rat.
Shiota M, Printz RL
(2012) Methods Mol Biol 933: 103-23
MeSH Terms: Animals, Diabetes Complications, Diabetes Mellitus, Type 2, Disease Models, Animal, Glucose, Hyperglycemia, Insulin Resistance, Insulin-Secreting Cells, Male, Obesity, Phenotype, Rats, Rats, Zucker, Receptors, Leptin
Show Abstract · Added February 19, 2015
Male Zucker diabetic fatty fa/fa (ZDF) rats develop obesity and insulin resistance at a young age, and then with aging, progressively develop hyperglycemia. This hyperglycemia is associated with impaired pancreatic β-cell function, loss of pancreatic β-cell mass, and decreased responsiveness of liver and extrahepatic tissues to the actions of insulin and glucose. Of particular interest are the insights provided by studies of these animals into the mechanism behind the progressive impairment of carbohydrate metabolism. This feature among others, including the development of obesity- and hyperglycemia-related complications, is common between male ZDF rats and humans with type 2 diabetes associated with obesity. We discuss the diabetic features and complications found in ZDF rats and why these animals are widely used as a genetic model for obese type 2 diabetes.
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14 MeSH Terms
Emerging role of AMP-activated protein kinase in endocrine control of metabolism in the liver.
Hasenour CM, Berglund ED, Wasserman DH
(2013) Mol Cell Endocrinol 366: 152-62
MeSH Terms: AMP-Activated Protein Kinases, Adiponectin, Animals, Endocrine System, Energy Metabolism, Gene Expression Regulation, Ghrelin, Glucagon, Glucose, Humans, Insulin, Leptin, Liver, Mice, Resistin, Signal Transduction
Show Abstract · Added March 18, 2013
This review summarizes the emerging role of AMP-activated protein kinase (AMPK) in mediating endocrine regulation of metabolic fluxes in the liver. There are a number of hormones which, when acting on the liver, alter AMPK activation. Here we describe those hormones associated with activation and de-activation of AMPK and the potential mechanisms for changes in AMPK activation state. The actions of these hormones, in many cases, are consistent with downstream effects of AMPK signaling thus strengthening the circumstantial case for AMPK-mediated hormone action. In recent years, genetic mouse models have also been used in an attempt to establish the role of AMPK in hormone-stimulated metabolism in the liver. Few experiments have, however, firmly established a causal relationship between hormone action at the liver and AMPK signaling.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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16 MeSH Terms
Effects of dietary composition on energy expenditure during weight-loss maintenance.
Ebbeling CB, Swain JF, Feldman HA, Wong WW, Hachey DL, Garcia-Lago E, Ludwig DS
(2012) JAMA 307: 2627-34
MeSH Terms: Adult, Cholesterol, HDL, Cross-Over Studies, Diet, Carbohydrate-Restricted, Diet, Fat-Restricted, Energy Metabolism, Female, Glycemic Index, Humans, Hydrocortisone, Insulin Resistance, Leptin, Male, Metabolic Syndrome, Nutritive Value, Obesity, Overweight, Plasminogen Activator Inhibitor 1, Triglycerides, Weight Loss, Young Adult
Show Abstract · Added March 20, 2014
CONTEXT - Reduced energy expenditure following weight loss is thought to contribute to weight gain. However, the effect of dietary composition on energy expenditure during weight-loss maintenance has not been studied.
OBJECTIVE - To examine the effects of 3 diets differing widely in macronutrient composition and glycemic load on energy expenditure following weight loss.
DESIGN, SETTING, AND PARTICIPANTS - A controlled 3-way crossover design involving 21 overweight and obese young adults conducted at Children's Hospital Boston and Brigham and Women's Hospital, Boston, Massachusetts, between June 16, 2006, and June 21, 2010, with recruitment by newspaper advertisements and postings.
INTERVENTION - After achieving 10% to 15% weight loss while consuming a run-in diet, participants consumed an isocaloric low-fat diet (60% of energy from carbohydrate, 20% from fat, 20% from protein; high glycemic load), low-glycemic index diet (40% from carbohydrate, 40% from fat, and 20% from protein; moderate glycemic load), and very low-carbohydrate diet (10% from carbohydrate, 60% from fat, and 30% from protein; low glycemic load) in random order, each for 4 weeks.
MAIN OUTCOME MEASURES - Primary outcome was resting energy expenditure (REE), with secondary outcomes of total energy expenditure (TEE), hormone levels, and metabolic syndrome components.
RESULTS - Compared with the pre-weight-loss baseline, the decrease in REE was greatest with the low-fat diet (mean [95% CI], -205 [-265 to -144] kcal/d), intermediate with the low-glycemic index diet (-166 [-227 to -106] kcal/d), and least with the very low-carbohydrate diet (-138 [-198 to -77] kcal/d; overall P = .03; P for trend by glycemic load = .009). The decrease in TEE showed a similar pattern (mean [95% CI], -423 [-606 to -239] kcal/d; -297 [-479 to -115] kcal/d; and -97 [-281 to 86] kcal/d, respectively; overall P = .003; P for trend by glycemic load < .001). Hormone levels and metabolic syndrome components also varied during weight maintenance by diet (leptin, P < .001; 24-hour urinary cortisol, P = .005; indexes of peripheral [P = .02] and hepatic [P = .03] insulin sensitivity; high-density lipoprotein [HDL] cholesterol, P < .001; non-HDL cholesterol, P < .001; triglycerides, P < .001; plasminogen activator inhibitor 1, P for trend = .04; and C-reactive protein, P for trend = .05), but no consistent favorable pattern emerged.
CONCLUSION - Among overweight and obese young adults compared with pre-weight-loss energy expenditure, isocaloric feeding following 10% to 15% weight loss resulted in decreases in REE and TEE that were greatest with the low-fat diet, intermediate with the low-glycemic index diet, and least with the very low-carbohydrate diet.
TRIAL REGISTRATION - clinicaltrials.gov Identifier: NCT00315354.
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21 MeSH Terms