scholarly journals TREM2 regulates obesity-induced insulin resistance via adipose tissue remodeling in mice of high-fat feeding

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Can Liu ◽  
Pinhao Li ◽  
Hui Li ◽  
Sicong Wang ◽  
Lifeng Ding ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Tissue Remodeling ◽  
High Fat ◽  
Adipose Tissue Remodeling ◽  
Fat Feeding

scholarly journals Loss of Oncostatin M Signaling in Adipocytes Induces Insulin Resistance and Adipose Tissue Inflammation in Vivo

2016 ◽  
Vol 291 (33) ◽  
pp. 17066-17076 ◽  
Author(s):  
Carrie M. Elks ◽  
Peng Zhao ◽  
Ryan W. Grant ◽  
Hardy Hang ◽  
Jennifer L. Bailey ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Cell Types ◽  
Oncostatin M ◽  
Adipose Tissue Inflammation ◽  
High Fat ◽  
Tissue Inflammation ◽  
Fat Feeding

Oncostatin M (OSM) is a multifunctional gp130 cytokine. Although OSM is produced in adipose tissue, it is not produced by adipocytes. OSM expression is significantly induced in adipose tissue from obese mice and humans. The OSM-specific receptor, OSM receptor β (OSMR), is expressed in adipocytes, but its function remains largely unknown. To better understand the effects of OSM in adipose tissue, we knocked down Osmr expression in adipocytes in vitro using siRNA. In vivo, we generated a mouse line lacking Osmr in adiponectin-expressing cells (OSMRFKO mice). The effects of OSM on gene expression were also assessed in vitro and in vivo. OSM exerts proinflammatory effects on cultured adipocytes that are partially rescued by Osmr knockdown. Osm expression is significantly increased in adipose tissue T cells of high fat-fed mice. In addition, adipocyte Osmr expression is increased following high fat feeding. OSMRFKO mice exhibit increased insulin resistance and adipose tissue inflammation and have increased lean mass, femoral length, and bone volume. Also, OSMRFKO mice exhibit increased expression of Osm, the T cell markers Cd4 and Cd8, and the macrophage markers F4/80 and Cd11c. Interestingly, the same proinflammatory genes induced by OSM in adipocytes are induced in the adipose tissue of the OSMRFKO mouse, suggesting that increased expression of proinflammatory genes in adipose tissue arises both from adipocytes and other cell types. These findings suggest that adipocyte OSMR signaling is involved in the regulation of adipose tissue homeostasis and that, in obesity, OSMR ablation may exacerbate insulin resistance by promoting adipose tissue inflammation.

scholarly journals PAPPA-mediated adipose tissue remodeling mitigates insulin resistance and protects against gestational diabetes in mice and humans

2020 ◽  
Vol 12 (571) ◽  
pp. eaay4145 ◽  
Author(s):  
Raziel Rojas-Rodriguez ◽  
Rachel Ziegler ◽  
Tiffany DeSouza ◽  
Sana Majid ◽  
Aylin S. Madore ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Gestational Diabetes ◽  
Signaling Pathway ◽  
Physiological State ◽  
Tissue Remodeling ◽  
Tissue Expansion ◽  
Dependent Manner ◽  
Adipose Tissue Remodeling

Pregnancy is a physiological state of continuous adaptation to changing maternal and fetal nutritional needs, including a reduction of maternal insulin sensitivity allowing for appropriately enhanced glucose availability to the fetus. However, excessive insulin resistance in conjunction with insufficient insulin secretion results in gestational diabetes mellitus (GDM), greatly increasing the risk for pregnancy complications and predisposing both mothers and offspring to future metabolic disease. Here, we report a signaling pathway connecting pregnancy-associated plasma protein A (PAPPA) with adipose tissue expansion in pregnancy. Adipose tissue plays a central role in the regulation of insulin sensitivity, and we show that, in both mice and humans, pregnancy caused remodeling of adipose tissue evidenced by altered adipocyte size, vascularization, and in vitro expansion capacity. PAPPA is known to be a metalloprotease secreted by human placenta that modulates insulin-like growth factor (IGF) bioavailability through prolteolysis of IGF binding proteins (IGFBPs) 2, 4, and 5. We demonstrate that recombinant PAPPA can stimulate ex vivo human adipose tissue expansion in an IGFBP-5– and IGF-1–dependent manner. Moreover, mice lacking PAPPA displayed impaired adipose tissue remodeling, pregnancy-induced insulin resistance, and hepatic steatosis, recapitulating multiple aspects of human GDM. In a cohort of 6361 pregnant women, concentrations of circulating PAPPA are inversely correlated with glycemia and odds of developing GDM. These data identify PAPPA and the IGF signaling pathway as necessary for the regulation of maternal adipose tissue physiology and systemic glucose homeostasis, with consequences for long-term metabolic risk and potential for therapeutic use.

scholarly journals Deletion of the Duffy antigen receptor for chemokines (DARC) promotes insulin resistance and adipose tissue inflammation during high fat feeding

2018 ◽  
Vol 473 ◽  
pp. 79-88 ◽  
Author(s):  
Tyler W. Benson ◽  
Daniel S. Weintraub ◽  
Matthew Crowe ◽  
Nicole K.H. Yiew ◽  
Orishebawo Popoola ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Antigen Receptor ◽  
Adipose Tissue Inflammation ◽  
High Fat ◽  
Tissue Inflammation ◽  
Duffy Antigen ◽  
Fat Feeding

scholarly journals Effects of Pioglitazone on Adipose Tissue Remodeling Within the Setting of Obesity and Insulin Resistance

Diabetes ◽  
2001 ◽  
Vol 50 (8) ◽  
pp. 1863-1871 ◽  
Author(s):  
C. J. de Souza ◽  
M. Eckhardt ◽  
K. Gagen ◽  
M. Dong ◽  
W. Chen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Tissue Remodeling ◽  
Adipose Tissue Remodeling

Regulation of adiponectin and its receptors in response to development of diet-induced obesity in mice

2007 ◽  
Vol 292 (4) ◽  
pp. E1079-E1086 ◽  
Author(s):  
John W. Bullen ◽  
Susann Bluher ◽  
Theodoros Kelesidis ◽  
Christos S. Mantzoros
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Adiponectin Mrna ◽  
Obesity In Mice ◽  
Fat Feeding

Adiponectin and its receptors play an important role in energy homeostasis and insulin resistance, but their regulation remains to be fully elucidated. We hypothesized that high-fat diet would decrease adiponectin but increase adiponectin receptor (AdipoR1 and AdipoR2) expression in diet-induced obesity (DIO)-prone C57BL/6J and DIO-resistant A/J mice. We found that circulating adiponectin and adiponectin expression in white adipose tissue are higher at baseline in C57BL/6J mice compared with A/J mice. Circulating adiponectin increases at 10 wk but decreases at 18 wk in response to advancing age and high-fat feeding. However, adiponectin levels corrected for visceral fat mass and adiponectin mRNA expression in WAT are affected by high-fat feeding only, with both being decreased after 10 wk in C57BL/6J mice. Muscle AdipoR1 expression in both C57BL/6J and A/J mice and liver adipoR1 expression in C57BL/6J mice increase at 18 wk of age. High-fat feeding increases both AdipoR1 and AdipoR2 expression in liver in both strains of mice and increases muscle AdipoR1 expression in C57BL/6J mice after 18 wk. Thus advanced age and high-fat feeding, both of which are factors that predispose humans to obesity and insulin resistance, are associated with decreasing adiponectin and increasing AdipoR1 and/or AdipoR2 levels.

scholarly journals Intermittent Fasting Improves Glucose Tolerance and Promotes Adipose Tissue Remodeling in Male Mice Fed a High-Fat Diet

Endocrinology ◽  
2018 ◽  
Vol 160 (1) ◽  
pp. 169-180 ◽  
Author(s):  
Bo Liu ◽  
Amanda J Page ◽  
George Hatzinikolas ◽  
Miaoxin Chen ◽  
Gary A Wittert ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Tissue Remodeling ◽  
Intermittent Fasting ◽  
Male Mice ◽  
High Fat ◽  
Adipose Tissue Remodeling

scholarly journals TRPM2 Ca2+ channel regulates energy balance and glucose metabolism

2012 ◽  
Vol 302 (7) ◽  
pp. E807-E816 ◽  
Author(s):  
Zhiyou Zhang ◽  
Wenyi Zhang ◽  
Dae Young Jung ◽  
Hwi Jin Ko ◽  
Yongjin Lee ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Gsk 3Β ◽  
Fat Feeding

TRPM2 Ca2+-permeable cation channel is widely expressed and activated by markers of cellular stress. Since inflammation and stress play a major role in insulin resistance, we examined the role of TRPM2 Ca2+ channel in glucose metabolism. A 2-h hyperinsulinemic euglycemic clamp was performed in TRPM2-deficient (KO) and wild-type mice to assess insulin sensitivity. To examine the effects of diet-induced obesity, mice were fed a high-fat diet for 4–10 mo, and metabolic cage and clamp studies were conducted in conscious mice. TRPM2-KO mice were more insulin sensitive partly because of increased glucose metabolism in peripheral organs. After 4 mo of high-fat feeding, TRPM2-KO mice were resistant to diet-induced obesity, and this was associated with increased energy expenditure and elevated expressions of PGC-1α, PGC-1β, PPARα, ERRα, TFAM, and MCAD in white adipose tissue. Hyperinsulinemic euglycemic clamps showed that TRPM2-KO mice were more insulin sensitive, with increased Akt and GSK-3β phosphorylation in heart. Obesity-mediated inflammation in adipose tissue and liver was attenuated in TRPM2-KO mice. Overall, TRPM2 deletion protected mice from developing diet-induced obesity and insulin resistance. Our findings identify a novel role of TRPM2 Ca2+ channel in the regulation of energy expenditure, inflammation, and insulin resistance.

Sign in / Sign up

Export Citation Format

Share Document