scholarly journals B-Cell-Activating Factor Depletion Ameliorates Aging-Dependent Insulin Resistance via Enhancement of Thermogenesis in Adipose Tissues

2020 ◽  
Vol 21 (14) ◽  
pp. 5121
Author(s):  
Bobae Kim ◽  
Chang-Kee Hyun
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
B Cell ◽  
Adipose Tissues ◽  
B Cell Activating Factor ◽  
Proliferation And Differentiation ◽  
Regulated Expression ◽  
Cold Challenge ◽  
Subcutaneous Adipose ◽  
Deficient Mice

Impaired glucose tolerance is a common feature associated with human aging, which is caused by defects in insulin secretion, insulin action or both. Recent studies have suggested that B-cell-activating factor (BAFF), a cytokine that modulates proliferation and differentiation of B cells, and its receptors are expressed in mature adipocytes and preadipocytes, proposing BAFF as a potential regulator of energy metabolism. In this study, we show that systemic BAFF depletion improves aging-dependent insulin resistance. In aged (10-month-old) BAFF−/− mice, glucose tolerance and insulin sensitivity were significantly improved despite higher adiposity as a result of expansion of adipose tissues compared to wild-type controls. BAFF−/− mice displayed an improved response to acute cold challenge, commensurate with the up-regulated expression of thermogenic genes in both brown and subcutaneous adipose tissues. These changes were found to be mediated by both increased M2-like (alternative) macrophage activation and enhanced leptin and FGF21 production, which may account for the improving effect of BAFF depletion on insulin resistance. In addition, leptin-deficient mice (ob/ob) showed augmented BAFF signaling concomitant with impaired thermogenic activity, identifying BAFF as a suppressive factor to thermogenesis. Our findings suggest that suppression of BAFF could be a therapeutic approach to attenuate aging-dependent insulin resistance.

scholarly journals Dietary glycemic index and dietary glycemic load is associated with apelin gene expression in visceral and subcutaneous adipose tissues of adults

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Emad Yuzbashian ◽  
Golaleh Asghari ◽  
Maryam Aghayan ◽  
Mehdi Hedayati ◽  
Maryam Zarkesh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Glycemic Index ◽  
Glycemic Load ◽  
Carbohydrate Intake ◽  
Model Assessment ◽  
Total Carbohydrate ◽  
Adipose Tissues ◽  
Visceral Adipose ◽  
Subcutaneous Adipose

Abstract Background Apelin, as an adipokine, plays an important role in the pathogenesis of insulin resistance and type 2 diabetes. This study aimed to determine whether the quality and quantity of dietary carbohydrates were associated with apelin gene expression in subcutaneous and visceral adipose tissues. Methods In this cross-sectional study, 102 adults who underwent minor abdominal surgery were selected. Approximately 100 mg of subcutaneous and visceral adipose tissues were collected during the surgery to measure apelin gene expression. Anthropometric measurment, blood samples, and dietary intakes were collected before surgery. The dietary carbohydrate intake, glycemic index (GI), and glycemic load (GL) were determined. Results The average apelin concentration was 269.6 ± 98.5(pg/mL), and 16.3% of participants were insulin resistant. There was a correlation between insulin (p-value = 0.043), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)(p-value = 0.045) and apelin gene expression in visceral adipose tissue. There was a positive association of apelin gene expression with dietary GI and GL after adjustment for age, sex, and waist circumference in visceral and subcutaneous adipose tissues(p < 0.05). Apelin gene expression in visceral(p = 0.002) and subcutaneous(p = 0.003) adipose tissues was directly associated with foods with a higher GI. There was no association between total carbohydrate intake and apelin gene expression in both visceral and subcutaneous adipose tissues. Conclusions Dietary GI and GL, not total carbohydrate intake, were positively associated with apelin gene expression in both visceral and subcutaneous adipose tissues. Future studies are warranted to illustrate the chronic and acute effect of carbohydrate quality on apelin homeostasis.

scholarly journals MON-639 Melanocortin 4 Receptor Contributes to Glucose Homeostasis by Regulating Kidney Glucose Reabsorption via the Glucose Transporter GLUT2

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Leticia M de Souza Cordeiro ◽  
Nagavardhini Devisetty ◽  
Kavaljit H Chhabra
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Molecular Mechanisms ◽  
Area Under The Curve ◽  
Glucose Transporters ◽  
Oral Glucose ◽  
Melanocortin 4 Receptor ◽  
Glucose Reabsorption ◽  
Deficient Mice

Abstract Melanocortin 4 receptor (MC4R) is essential for normal body weight and food intake. Deficiency of MC4R causes obesity in humans and mice. While the function of MC4R is well established in appetite regulation, its direct role in glucose homeostasis is unclear. Humans and mice with MC4R deficiency exhibit hyperinsulinemia and insulin resistance; however, they remain protected from fasting hyperglycemia/diabetes. To determine the role of MC4R in glucose homeostasis, we performed oral glucose and intra-peritoneal insulin tolerance tests (OGTT / ITT) in male and female Mc4r knockout (KO) and wild type (WT) mice. Remarkably, Mc4r KO mice exhibited improved glucose tolerance compared to WT mice (Area under the curve for OGTT, male: 29,125±2,028 vs. 38,493±1,161 mg/dL.min; female: 36,322±1,100 vs. 49,539±1,911 mg/dL.min, p&lt;0.0001). The improvement in glucose tolerance was despite insulin resistance in Mc4r KO mice (Plasma insulin, male: 9.9±1.7 vs. 0.7±0.1 ng/mL, female: 6.2±2.0 vs. 1.1±0.3 ng/mL, p&lt;0.05; Area under the curve for ITT, male: 13,174±1,073 vs. 8,132±255 mg/dL.min; female: 13,927±1,253 vs. 7,506±267 mg/dL.min, p&lt;0.01). Based on our previous findings from POMC deficient mice, we hypothesized that the improved glucose tolerance in the Mc4r KO mice is due to their elevated glycosuria (excretion of glucose in urine). To test this hypothesis, we challenged Mc4r KO and WT mice with oral glucose (250 mg) and collected their 24h urine to evaluate glycosuria. Indeed, the KO mice demonstrated elevated glycosuria compared to their WT littermates (Urine glucose, male: 284±48 vs. 0.4±0.03 mg/24h, female: 63.4±14 vs. 1±0.6 mg/24h, p&lt;0.002). To assess molecular mechanisms underlying elevated glycosuria in Mc4r KO mice, we measured the gene expression and levels of the kidney glucose transporters GLUT1, GLUT2, SGLT1 and SGLT2. Glut2 mRNA was reduced by ̴ 40% and the protein level was decreased by ̴ 20% in Mc4r KO mice compared to their WT littermates. The other glucose transporters remained unchanged. Altogether, our study demonstrates that MC4R contributes to glucose homeostasis by regulating kidney glucose reabsorption via GLUT2. These findings may explain why MC4R deficient mice or humans remain protected from diabetes despite their longstanding obesity and insulin resistance.

scholarly journals B Cell-Activating Factor Controls the Production of Adipokines and Induces Insulin Resistance

Obesity ◽  
2011 ◽  
Vol 19 (10) ◽  
pp. 1915-1922 ◽  
Author(s):  
Maho Hamada ◽  
Masanori Abe ◽  
Teruki Miyake ◽  
Keitarou Kawasaki ◽  
Fujimasa Tada ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
B Cell ◽  
B Cell Activating Factor

scholarly journals Persistent Friend Virus Replication and Disease in Apobec3-Deficient Mice Expressing Functional B-Cell-Activating Factor Receptor

2010 ◽  
Vol 85 (1) ◽  
pp. 189-199 ◽  
Author(s):  
M. L. Santiago ◽  
D. S. Smith ◽  
B. S. Barrett ◽  
M. Montano ◽  
R. L. Benitez ◽  
...  
Keyword(s):  
B Cell ◽  
Virus Replication ◽  
Friend Virus ◽  
B Cell Activating Factor ◽  
Deficient Mice

scholarly journals NOD1 expression is increased in the adipose tissue of women with gestational diabetes

2014 ◽  
Vol 222 (1) ◽  
pp. 99-112 ◽  
Author(s):  
Martha Lappas
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Gestational Diabetes ◽  
Diaminopimelic Acid ◽  
Adipose Tissues ◽  
Prostaglandin Production ◽  
Insulin Signalling Pathway ◽  
Wide Range ◽  
Subcutaneous Adipose

Maternal peripheral insulin resistance and increased inflammation are two features of pregnancies, complicated by gestational diabetes mellitus (GDM). The nucleotide-binding oligomerisation domain (NOD) intracellular molecules recognise a wide range of microbial products, as well as other intracellular danger signals, thereby initiating inflammation through activation of nuclear factor κB (NFκB). The aim of this study was to determine whether levels of NOD1 and NOD2 are increased in adipose tissue of women with GDM. The effect of NOD1 and NOD2 activation on inflammation and the insulin signalling pathway was also assessed. NOD1, but not NOD2, expression was higher in omental and subcutaneous adipose tissues obtained from women with GDM when compared with those from women with normal glucose tolerance (NGT). In both omental and subcutaneous adipose tissues from NGT and GDM women, the NOD1 ligand g-d-glutamyl-meso-diaminopimelic acid (iE-DAP) significantly induced the expression and secretion of the pro-inflammatory cytokine interleukin 6 (IL6) and chemokine IL8;COX2(PTGS2) gene expression and subsequent prostaglandin production; the expression and secretion of the extracellular matrix remodelling enzyme matrix metalloproteinase 9 (MMP9) and the gene expression and secretion of the adhesion moleculesICAM1andVCAM1. There was no effect of the NOD2 ligand muramyl dipeptide on any of the endpoints tested. The effects of the NOD1 ligand iE-DAP were mediated via NFκB, as the NFκB inhibitor BAY 11-7082 significantly attenuated iE-DAP-induced expression and secretion of pro-inflammatory cytokines,COX2gene expression and subsequent prostaglandin production,MMP9expression and secretion andICAM1andVCAM1gene expression and secretion. In conclusion, the present findings describe an important role for NOD1 in the development of insulin resistance and inflammation in pregnancies complicated by GDM.

Impaired B-cell development at the pre-BII-cell stage in galectin-1–deficient mice due to inefficient pre-BII/stromal cell interactions

Blood ◽  
2009 ◽  
Vol 113 (23) ◽  
pp. 5878-5886 ◽  
Author(s):  
Marion Espeli ◽  
Stéphane J. C. Mancini ◽  
Caroline Breton ◽  
Françoise Poirier ◽  
Claudine Schiff
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
Cell Differentiation ◽  
B Cell ◽  
Stromal Cell ◽  
Cell Phenotype ◽  
Cell Proliferation And Differentiation ◽  
Hydroxyurea Treatment ◽  
Proliferation And Differentiation ◽  
Deficient Mice

Abstract Activation of the pre-B-cell receptor (pre-BCR) in the bone marrow depends on both tonic and ligand-induced signaling and leads to pre-BII-cell proliferation and differentiation. Using normal mouse bone marrow pre-BII cells, we demonstrate that the ligand-induced pre-BCR activation depends on pre-BCR/galectin-1/integrin interactions leading to pre-BCR clustering at the pre-BII/stromal cell synapse. In contrast, heparan sulfates, shown to be pre-BCR ligands in mice, are not implicated in pre-BCR relocalization. Inhibition of pre-BCR/galectin-1/integrin interactions has functional consequences, since pre-BII-cell proliferation and differentiation are impaired in an in vitro B-cell differentiation assay, without affecting cellular apoptosis. Most strikingly, although galectin-1–deficient mice do not show an apparent B-cell phenotype, the kinetics of de novo B-cell reconstitution after hydroxyurea treatment indicates a specific delay in pre-BII-cell recovery due to a decrease in pre-BII-cell differentiation and proliferation. Thus, although it remains possible that the pre-BCR interacts with other ligands, these results highlight the role played by the stromal cell–derived galectin-1 for the efficient development of normal pre-BII cells and suggest the existence of pre-BII–specific stromal cell niches in normal bone marrow.

scholarly journals The ratio of pericardial to subcutaneous adipose tissues is associated with insulin resistance

Obesity ◽  
2017 ◽  
Vol 25 (7) ◽  
pp. 1284-1291 ◽  
Author(s):  
Amy C. Alman ◽  
Steven R. Smith ◽  
Robert H. Eckel ◽  
John E. Hokanson ◽  
Brant R. Burkhardt ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissues ◽  
Subcutaneous Adipose

Effects of resveratrol on the amelioration of insulin resistance in KKAy mice

2012 ◽  
Vol 90 (2) ◽  
pp. 237-242 ◽  
Author(s):  
Sifan Chen ◽  
Jinghua Li ◽  
Zili Zhang ◽  
Wenxue Li ◽  
Yanshuang Sun ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Protein Kinase ◽  
Glucose Tolerance ◽  
Serum Insulin ◽  
Underlying Mechanism ◽  
Mrna Levels ◽  
Adipose Tissues ◽  
Adiponectin Mrna

Resveratrol (Res) has attracted great interest regarding its effects related to metabolic syndrome, especially for lipid metabolic disorder or insulin resistance; however, the underlying mechanisms remain elusive. To explore the effects of Res on insulin sensitivity and the underlying mechanism, insulin-resistant KKAy mice were treated with 2 and 4 g/kg diets of Res for 12 weeks. After the treatment, blood glucose, serum insulin, glucose tolerance, and insulin tolerance, as well as other indices such as adiponectin mRNA in epididymal adipose tissues, silent information regulator 1 (Sirt1), AMP-activated protein kinase (AMPK), insulin receptor substrate 1 (IRS1), and phosphorylated protein kinase B (PKB/AKT) proteins in liver and soleus muscles, were investigated. The results indicate that Res intervention reduces blood glucose and serum insulin levels, improves insulin and glucose tolerance, increases serum adiponectin and adiponectin mRNA levels in epididymal adipose tissues, and more importantly, elevates Sirt1, p-AMPK, p-IRS1, and p-AKT levels in liver and soleus muscles. In conclusion, Res could improve insulin sensitivity and ameliorate insulin resistance in KKAy mice, which may be associated with the upregulation of Sirt1 protein in liver and soleus muscles and consequent AMPK activation, as well as insulin-signaling related proteins.

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