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Obesity-induced reduction of adipose eosinophils is reversed with low-calorie dietary intervention.
Bolus WR, Kennedy AJ, Hasty AH
(2018) Physiol Rep 6: e13919
MeSH Terms: Adipose Tissue, Animals, Caloric Restriction, Cells, Cultured, Eosinophils, Male, Mice, Mice, Inbred C57BL, Obesity, Weight Loss
Show Abstract · Added March 26, 2019
While many studies have characterized the inflammatory disposition of adipose tissue (AT) during obesity, far fewer have dissected how such inflammation resolves during the process of physiological weight loss. In addition, new immune cells, such as the eosinophil, have been discovered as part of the AT immune cell repertoire. We have therefore characterized how AT eosinophils, associated eosinophilic inflammation, and remodeling processes, fluctuate during a dietary intervention in obese mice. Similar to previous reports, we found that obesity induced by high-fat diet feeding reduced the AT eosinophil content. However, upon switching obese mice to a low fat diet, AT eosinophils were restored to lean levels as mice reached the body weight of controls. The rise in AT eosinophils during dietary weight loss was accompanied by reduced macrophage content and inflammatory expression, upregulated tissue remodeling factors, and a more uniformly distributed AT vascular network. Additionally, we show that eosinophils of another metabolically relevant tissue, the liver, did not oscillate with either dietary weight gain or weight loss. This study shows that eosinophil content is differentially regulated among tissues during the onset and resolution of obesity. Furthermore, AT eosinophils correlated with AT remodeling processes during weight loss and thus may play a role in reestablishing AT homeostasis.
© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
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10 MeSH Terms
Role of Bile Acids and GLP-1 in Mediating the Metabolic Improvements of Bariatric Surgery.
Albaugh VL, Banan B, Antoun J, Xiong Y, Guo Y, Ping J, Alikhan M, Clements BA, Abumrad NN, Flynn CR
(2019) Gastroenterology 156: 1041-1051.e4
MeSH Terms: Anastomosis, Surgical, Animals, Anticholesteremic Agents, Bariatric Surgery, Bile Acids and Salts, Blood Glucose, Cholestyramine Resin, Diet, High-Fat, Gallbladder, Glucagon-Like Peptide 1, Glucagon-Like Peptide-1 Receptor, Glucose Tolerance Test, Ileum, Insulin Resistance, Intestines, Lymph, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, Cytoplasmic and Nuclear, Receptors, G-Protein-Coupled, Signal Transduction, Verrucomicrobia, Weight Loss
Show Abstract · Added January 4, 2019
BACKGROUND & AIMS - Bile diversion to the ileum (GB-IL) has strikingly similar metabolic and satiating effects to Roux-en-Y gastric bypass (RYGB) in rodent obesity models. The metabolic benefits of these procedures are thought to be mediated by increased bile acids, although parallel changes in body weight and other confounding variables limit this interpretation.
METHODS - Global G protein-coupled bile acid receptor-1 null (Tgr5) and intestinal-specific farnesoid X receptor null (Fxr) mice on high-fat diet as well as wild-type C57BL/6 and glucagon-like polypeptide 1 receptor deficient (Glp-1r) mice on chow diet were characterized following GB-IL.
RESULTS - GB-IL induced weight loss and improved oral glucose tolerance in Tgr5, but not Fxr mice fed a high-fat diet, suggesting a role for intestinal Fxr. GB-IL in wild-type, chow-fed mice prompted weight-independent improvements in glycemia and glucose tolerance secondary to augmented insulin responsiveness. Improvements were concomitant with increased levels of lymphatic GLP-1 in the fasted state and increased levels of intestinal Akkermansia muciniphila. Improvements in fasting glycemia after GB-IL were mitigated with exendin-9, a GLP-1 receptor antagonist, or cholestyramine, a bile acid sequestrant. The glucoregulatory effects of GB-IL were lost in whole-body Glp-1r mice.
CONCLUSIONS - Bile diversion to the ileum improves glucose homeostasis via an intestinal Fxr-Glp-1 axis. Altered intestinal bile acid availability, independent of weight loss, and intestinal Akkermansia muciniphila appear to mediate the metabolic changes observed after bariatric surgery and might be manipulated for treatment of obesity and diabetes.
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.
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25 MeSH Terms
CalR: A Web-Based Analysis Tool for Indirect Calorimetry Experiments.
Mina AI, LeClair RA, LeClair KB, Cohen DE, Lantier L, Banks AS
(2018) Cell Metab 28: 656-666.e1
MeSH Terms: Analysis of Variance, Animals, Calorimetry, Indirect, Cloud Computing, Data Visualization, Energy Metabolism, Humans, Linear Models, Mice, Obesity, Pulmonary Gas Exchange, Reproducibility of Results, Thermogenesis, Web Browser, Weight Loss, Workflow
Show Abstract · Added May 16, 2019
We report a web-based tool for analysis of experiments using indirect calorimetry to measure physiological energy balance. CalR simplifies the process to import raw data files, generate plots, and determine the most appropriate statistical tests for interpretation. Analysis using the generalized linear model (which includes ANOVA and ANCOVA) allows for flexibility in interpreting diverse experimental designs, including those of obesity and thermogenesis. Users also may produce standardized output files for an experiment that can be shared and subsequently re-evaluated using CalR. This framework will provide the transparency necessary to enhance consistency, rigor, and reproducibility. The CalR analysis software will greatly increase the speed and efficiency with which metabolic experiments can be organized, analyzed per accepted norms, and reproduced and will likely become a standard tool for the field. CalR is accessible at https://CalRapp.org/.
Copyright © 2018 Elsevier Inc. All rights reserved.
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16 MeSH Terms
The Vasculature in Prediabetes.
Wasserman DH, Wang TJ, Brown NJ
(2018) Circ Res 122: 1135-1150
MeSH Terms: Angiotensin-Converting Enzyme Inhibitors, Animals, Blood Vessels, Cardiovascular Diseases, Combined Modality Therapy, Diabetes Mellitus, Type 2, Diet, Reducing, Disease Progression, Endothelium, Vascular, Extracellular Matrix, Fatty Acids, Nonesterified, Fibrinolysis, Glucose, Humans, Hyperglycemia, Hypoglycemic Agents, Inflammation, Insulin Resistance, Life Style, Metabolic Syndrome, Mice, MicroRNAs, Microcirculation, Muscle, Skeletal, Obesity, Prediabetic State, Risk, Weight Loss
Show Abstract · Added March 26, 2019
The frequency of prediabetes is increasing as the prevalence of obesity rises worldwide. In prediabetes, hyperglycemia, insulin resistance, and inflammation and metabolic derangements associated with concomitant obesity cause endothelial vasodilator and fibrinolytic dysfunction, leading to increased risk of cardiovascular and renal disease. Importantly, the microvasculature affects insulin sensitivity by affecting the delivery of insulin and glucose to skeletal muscle; thus, endothelial dysfunction and extracellular matrix remodeling promote the progression from prediabetes to diabetes mellitus. Weight loss is the mainstay of treatment in prediabetes, but therapies that improved endothelial function and vasodilation may not only prevent cardiovascular disease but also slow progression to diabetes mellitus.
© 2018 American Heart Association, Inc.
1 Communities
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28 MeSH Terms
Reduced Nonexercise Activity Attenuates Negative Energy Balance in Mice Engaged in Voluntary Exercise.
Lark DS, Kwan JR, McClatchey PM, James MN, James FD, Lighton JRB, Lantier L, Wasserman DH
(2018) Diabetes 67: 831-840
MeSH Terms: Animals, Behavior, Animal, Calorimetry, Indirect, Energy Intake, Energy Metabolism, Male, Mice, Mice, Inbred C57BL, Motor Activity, Obesity, Physical Conditioning, Animal, Weight Loss
Show Abstract · Added March 26, 2019
Exercise alone is often ineffective for treating obesity despite the associated increase in metabolic requirements. Decreased nonexercise physical activity has been implicated in this resistance to weight loss, but the mechanisms responsible are unclear. We quantified the metabolic cost of nonexercise activity, or "off-wheel" activity (OWA), and voluntary wheel running (VWR) and examined whether changes in OWA during VWR altered energy balance in chow-fed C57BL/6J mice ( = 12). Energy expenditure (EE), energy intake, and behavior (VWR and OWA) were continuously monitored for 4 days with locked running wheels followed by 9 days with unlocked running wheels. Unlocking the running wheels increased EE as a function of VWR distance. The metabolic cost of exercise (kcal/m traveled) decreased with increasing VWR speed. Unlocking the wheel led to a negative energy balance but also decreased OWA, which was predicted to mitigate the expected change in energy balance by ∼45%. A novel behavioral circuit involved repeated bouts of VWR, and roaming was discovered and represented novel predictors of VWR behavior. The integrated analysis described here reveals that the weight loss effects of voluntary exercise can be countered by a reduction in nonexercise activity.
© 2018 by the American Diabetes Association.
1 Communities
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MeSH Terms
Late-Life Body Mass Index, Rapid Weight Loss, Apolipoprotein E ε4 and the Risk of Cognitive Decline and Incident Dementia.
Bell SP, Liu D, Samuels LR, Shah AS, Gifford KA, Hohman TJ, Jefferson AL
(2017) J Nutr Health Aging 21: 1259-1267
MeSH Terms: Aged, Aged, 80 and over, Alzheimer Disease, Apolipoprotein E4, Body Mass Index, Cognitive Dysfunction, Cohort Studies, Dementia, Female, Humans, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Weight Loss
Show Abstract · Added March 16, 2018
OBJECTIVES - To examine the effect of late-life body mass index (BMI) and rapid weight loss on incident mild cognitive impairment (MCI) and Alzheimer's disease (AD).
DESIGN - Prospective longitudinal cohort study.
SETTING - National Alzheimer's Coordinating Center (NACC) Uniform Data Set, including 34 past and current National Institute on Aging-funded AD Centers across the United States.
PARTICIPANTS - 6940 older adults (n=5061 normal cognition [NC]; n=1879 MCI).
MEASUREMENTS - BMI (kg/m2) and modified Framingham Stroke Risk Profile (FSRP) score (sex, age, systolic blood pressure, anti-hypertension medication, diabetes mellitus, cigarette smoking, prevalent cardiovascular disease, atrial fibrillation) were assessed at baseline. Cognition and weight were assessed annually.
RESULTS - Multivariable binary logistic regression, adjusting for age, sex, race, education, length of follow-up, and modified FSRP related late-life BMI to risk of diagnostic conversion from NC to MCI or AD and from MCI to AD. Secondary analyses related late-life BMI to diagnostic conversion in the presence of rapid weight loss (>5% decrease in 12 months) and apolipoprotein E (APOE) ε4. During a mean 3.8-year follow-up period, 12% of NC participants converted to MCI or AD and 49% of MCI participants converted to AD. Higher baseline BMI was associated with a reduced probability of diagnostic conversion, such that for each one-unit increase in baseline BMI there was a reduction in diagnostic conversion for both NC (OR=0.977, 95%CI 0.958-0.996, p=0.015) and MCI participants (OR=0.962, 95%CI 0.942-0.983, p<0.001). The protective effect of higher baseline BMI did not persist in the setting of rapid weight loss but did persist when adjusting for APOE ε4.
CONCLUSIONS - Higher late-life BMI is associated with a lower risk of incident MCI and AD but is not protective in the presence of rapid weight loss.
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15 MeSH Terms
Diabetes Education, Specialty Care, and Self-Care Advice among Obese African American Women with Type 2 Diabetes.
Miller ST, Cunningham-Erves J, Akohoue SA
(2016) Ethn Dis 26: 229-34
MeSH Terms: Adult, African Americans, Chi-Square Distribution, Counseling, Diabetes Mellitus, Type 2, Diet, Exercise, Female, Health Education, Humans, Middle Aged, Obesity, Self Care, Self Report, Weight Loss
Show Abstract · Added July 28, 2016
OBJECTIVE - Healthy People 2020 (HP2020) includes benchmarks for diabetes management. The objective of our study was to describe diabetes management among African American women, a patient group that carries a disproportionate diabetes burden.
PARTICIPANTS - African American women with type 2 diabetes enrolled in dietary and weight management interventions.
MAIN OUTCOME MEASURES - Self-report assessments of diabetes education, specialty care, self-care behaviors and advice. Associations between diabetes self-care behaviors and diabetes advice using Chi-square tests.
RESULTS - Among 96 participants (age = 53 ± 9.4; BMI = 37.9 ± 7.3 kg/m(2)), reported diabetes education and foot exams were lower than HP2020 benchmarks, 48.9% vs 62.5% and 35.1% vs 74.8%, respectively and higher for dilated eye exams (70.1% vs 58.7%). The most frequently reported dietary advice was to increase fruit/vegetable intake (58%) and approximately 50% reported physical activity advice. Receiving no exercise advice was associated with greater odds of little or no physical activity (OR = 3.38) and planned exercises (OR = 2.65).
CONCLUSIONS - Receipt of diabetes education and some specialty care were below national benchmarks while health care provider advice influenced patient self-care behaviors. Increasing diabetes education and specialty care should be included within existing efforts to address the excess diabetes burden experienced by African American women. Longitudinal studies exploring the relationship between health care provider advice and self-care behaviors are needed.
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15 MeSH Terms
Sustained Brown Fat Stimulation and Insulin Sensitization by a Humanized Bispecific Antibody Agonist for Fibroblast Growth Factor Receptor 1/βKlotho Complex.
Kolumam G, Chen MZ, Tong R, Zavala-Solorio J, Kates L, van Bruggen N, Ross J, Wyatt SK, Gandham VD, Carano RA, Dunshee DR, Wu AL, Haley B, Anderson K, Warming S, Rairdan XY, Lewin-Koh N, Zhang Y, Gutierrez J, Baruch A, Gelzleichter TR, Stevens D, Rajan S, Bainbridge TW, Vernes JM, Meng YG, Ziai J, Soriano RH, Brauer MJ, Chen Y, Stawicki S, Kim HS, Comps-Agrar L, Luis E, Spiess C, Wu Y, Ernst JA, McGuinness OP, Peterson AS, Sonoda J
(2015) EBioMedicine 2: 730-43
MeSH Terms: Adiponectin, Adipose Tissue, Brown, Animals, Antibodies, Bispecific, Cell Line, Energy Metabolism, Fibroblast Growth Factors, HEK293 Cells, Humans, Insulin, Macaca fascicularis, Male, Membrane Proteins, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Obese, Protein Binding, Receptor, Fibroblast Growth Factor, Type 1, Thermogenesis, Weight Loss
Show Abstract · Added September 10, 2015
Dissipating excess calories as heat through therapeutic stimulation of brown adipose tissues (BAT) has been proposed as a potential treatment for obesity-linked disorders. Here, we describe the generation of a humanized effector-less bispecific antibody that activates fibroblast growth factor receptor (FGFR) 1/βKlotho complex, a common receptor for FGF21 and FGF19. Using this molecule, we show that antibody-mediated activation of FGFR1/βKlotho complex in mice induces sustained energy expenditure in BAT, browning of white adipose tissue, weight loss, and improvements in obesity-associated metabolic derangements including insulin resistance, hyperglycemia, dyslipidemia and hepatosteatosis. In mice and cynomolgus monkeys, FGFR1/βKlotho activation increased serum high-molecular-weight adiponectin, which appears to contribute over time by enhancing the amplitude of the metabolic benefits. At the same time, insulin sensitization by FGFR1/βKlotho activation occurs even before the onset of weight loss in a manner that is independent of adiponectin. Together, selective activation of FGFR1/βKlotho complex with a long acting therapeutic antibody represents an attractive approach for the treatment of type 2 diabetes and other obesity-linked disorders through enhanced energy expenditure, insulin sensitization and induction of high-molecular-weight adiponectin.
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20 MeSH Terms
Early Increases in Bile Acids Post Roux-en-Y Gastric Bypass Are Driven by Insulin-Sensitizing, Secondary Bile Acids.
Albaugh VL, Flynn CR, Cai S, Xiao Y, Tamboli RA, Abumrad NN
(2015) J Clin Endocrinol Metab 100: E1225-33
MeSH Terms: Adolescent, Adult, Bile Acids and Salts, Blood Glucose, Body Mass Index, Fasting, Female, Follow-Up Studies, Gastric Bypass, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Obesity, Morbid, Treatment Outcome, Weight Loss, Young Adult
Show Abstract · Added August 26, 2015
CONTEXT - Roux-en-Y gastric bypass (RYGB) is the most effective treatment for morbid obesity and resolution of diabetes. Over the last decade, it has become well accepted that this resolution of diabetes occurs before significant weight loss; however, the mechanisms behind this effect remain unknown and could represent novel therapeutic targets for obesity and diabetes. Bile acids have been identified as putative mediators of these weight loss-independent effects.
OBJECTIVE - To identify the longitudinal changes in bile acids after RYGB, which may provide mechanistic insight into the weight loss-independent effects of RYGB.
DESIGN - Observational study before/after intervention.
SETTING - Academic medical center.
PATIENTS/PARTICIPANTS - Samples were collected from morbidly obese patients (n = 21) before and after RYGB.
INTERVENTION - RYGB.
MAIN OUTCOME MEASURES - Seventeen individual bile acid species were measured preoperatively and at 1, 6, 12, and 24 months postoperatively. Anthropometric, hormonal, and hyperinsulinemic-euglycemic clamp data were also examined to identify physiological parameters associated with bile acid changes.
RESULTS - Fasting total plasma bile acids increased after RYGB; however, increases were bimodal and were observed only at 1 (P < .05) and 24 months (P < .01). One-month increases were secondary to surges in ursodeoxycholic acid and its glycine and taurine conjugates, bacterially derived bile acids with putative insulin-sensitizing effects. Increases at 24 months were due to gradual rises in primary unconjugated bile acids as well as deoxycholic acid and its glycine conjugate. Plasma bile acid changes were not significantly associated with any anthropometric or hormonal measures, although hepatic insulin sensitivity was significantly improved at 1 month.
CONCLUSIONS - Overall findings suggest that bacterially derived bile acids may mediate the early improvements at 1 month after RYGB. Future studies should examine the changes in specific bile acid chemical species after bariatric procedures and bile acid-specific signaling changes.
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18 MeSH Terms
The Intensive Diet and Exercise for Arthritis (IDEA) trial: 18-month radiographic and MRI outcomes.
Hunter DJ, Beavers DP, Eckstein F, Guermazi A, Loeser RF, Nicklas BJ, Mihalko SL, Miller GD, Lyles M, DeVita P, Legault C, Carr JJ, Williamson JD, Messier SP
(2015) Osteoarthritis Cartilage 23: 1090-8
MeSH Terms: Aged, Body Mass Index, Combined Modality Therapy, Diet, Reducing, Disease Progression, Exercise Therapy, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Obesity, Osteoarthritis, Knee, Radiography, Severity of Illness Index, Single-Blind Method, Treatment Outcome, Weight Loss
Show Abstract · Added August 24, 2015
PURPOSE - Report the radiographic and magnetic resonance imaging (MRI) structural outcomes of an 18-month study of diet-induced weight loss, with or without exercise, compared to exercise alone in older, overweight and obese adults with symptomatic knee osteoarthritis (OA).
METHODS - Prospective, single-blind, randomized controlled trial that enrolled 454 overweight and obese (body mass index, BMI = 27-41 kg m(-2)) older (age ≥ 55 yrs) adults with knee pain and radiographic evidence of femorotibial OA. Participants were randomized to one of three 18-month interventions: diet-induced weight loss only (D); diet-induced weight loss plus exercise (D + E); or exercise-only control (E). X-rays (N = 325) and MRIs (N = 105) were acquired at baseline and 18 months follow-up. X-ray and MRI (cartilage thickness and semi-quantitative (SQ)) results were analyzed to compare change between groups at 18-month follow-up using analysis of covariance (ANCOVA) adjusted for baseline values, baseline BMI, and gender.
RESULTS - Mean baseline descriptive characteristics of the cohort included: age, 65.6 yrs; BMI 33.6 kg m(-2); 72% female; 81% white. There was no significant difference between groups in joint space width (JSW) loss; D -0.07 (SE 0.22) mm, D + E -0.27 (SE 0.22) mm and E -0.16 (SE 0.24) mm (P = 0.79). There was also no significant difference in MRI cartilage loss between groups; D -0.10(0.05) mm, D + E -0.13(0.04) mm and E -0.05(0.04) mm (P = 0.42).
CONCLUSION - Despite the potent effects of weight loss in this study on symptoms as well as mechanistic outcomes (such as joint compressive force and markers of inflammation), there was no statistically significant difference between the three active interventions on the rate of structural progression either on X-ray or MRI over 18-months.
Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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19 MeSH Terms