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 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

scholarly journals Adipose stem cells in obesity: challenges and opportunities

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Sunhye Shin ◽  
Asma S. El-Sabbagh ◽  
Brandon E. Lukas ◽  
Skylar J. Tanneberger ◽  
Yuwei Jiang
Keyword(s):  
Insulin Resistance ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Tissue Expansion ◽  
The Body ◽  
Adipose Stem Cells ◽  
Low Grade ◽  
Challenges And Opportunities ◽  
Adipose Tissue Remodeling

Abstract Adipose tissue, the storage of excessive energy in the body, secretes various proteins called adipokines, which connect the body’s nutritional status to the regulation of energy balance. Obesity triggers alterations of quantity and quality of various types of cells that reside in adipose tissue, including adipose stem cells (ASCs; referred to as adipose-derived stem/stromal cells in vitro). These alterations in the functionalities and properties of ASCs impair adipose tissue remodeling and adipose tissue function, which induces low-grade systemic inflammation, progressive insulin resistance, and other metabolic disorders. In contrast, the ability of ASCs to recruit new adipocytes when faced with caloric excess leads to healthy adipose tissue expansion, associated with lower amounts of inflammation, fibrosis, and insulin resistance. This review focuses on recent advances in our understanding of the identity of ASCs and their roles in adipose tissue development, homeostasis, expansion, and thermogenesis, and how these roles go awry in obesity. A better understanding of the biology of ASCs and their adipogenesis may lead to novel therapeutic targets for obesity and metabolic disease.

scholarly journals HIF-1α in Myeloid Cells Promotes Adipose Tissue Remodeling Toward Insulin Resistance

Diabetes ◽  
2016 ◽  
Vol 65 (12) ◽  
pp. 3649-3659 ◽  
Author(s):  
Akiko Takikawa ◽  
Arshad Mahmood ◽  
Allah Nawaz ◽  
Tomonobu Kado ◽  
Keisuke Okabe ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Myeloid Cells ◽  
Tissue Remodeling ◽  
Adipose Tissue Remodeling

scholarly journals Identification of a regulatory pathway inhibiting adipogenesis via RSPO2

2022 ◽  
Author(s):  
Hua Dong ◽  
Wenfei Sun ◽  
Yang Shen ◽  
Miroslav Baláz ◽  
Lucia Balázová ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Progenitor Cells ◽  
Glucose Homeostasis ◽  
De Novo ◽  
Tissue Expansion ◽  
Tissue Homeostasis ◽  
Regulatory Pathway ◽  
Single Cell Rna Sequencing ◽  
Adipose Tissue Remodeling

AbstractHealthy adipose tissue remodeling depends on the balance between de novo adipogenesis from adipogenic progenitor cells and the hypertrophy of adipocytes. De novo adipogenesis has been shown to promote healthy adipose tissue expansion, which confers protection from obesity-associated insulin resistance. Here, we define the role and trajectory of different adipogenic precursor subpopulations and further delineate the mechanism and cellular trajectory of adipogenesis, using single-cell RNA-sequencing datasets of murine adipogenic precursors. We identify Rspo2 as a functional regulator of adipogenesis, which is secreted by a subset of CD142+ cells to inhibit maturation of early progenitors through the receptor Lgr4. Increased circulating RSPO2 in mice leads to adipose tissue hypertrophy and insulin resistance and increased RSPO2 levels in male obese individuals correlate with impaired glucose homeostasis. Taken together, these findings identify a complex cellular crosstalk that inhibits adipogenesis and impairs adipose tissue homeostasis.

scholarly journals LMO3 reprograms visceral adipocyte metabolism during obesity

2021 ◽  
Author(s):  
Gabriel Wagner ◽  
Anna Fenzl ◽  
Josefine Lindroos-Christensen ◽  
Elisa Einwallner ◽  
Julia Husa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Visceral Adipose Tissue ◽  
Tissue Expansion ◽  
Oxidative Capacity ◽  
Glut4 Translocation ◽  
Mitochondrial Oxidative Capacity ◽  
Visceral Adipose

Abstract Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. We recently identified LIM domain only 3 (LMO3) in human mature visceral adipocytes; however, its function in these cells is currently unknown. The aim of this study was to determine the potential involvement of LMO3-dependent pathways in the modulation of key functions of mature adipocytes during obesity. Based on a recently engineered hybrid rAAV serotype Rec2 shown to efficiently transduce both brown adipose tissue (BAT) and white adipose tissue (WAT), we delivered YFP or Lmo3 to epididymal WAT (eWAT) of C57Bl6/J mice on a high-fat diet (HFD). The effects of eWAT transduction on metabolic parameters were evaluated 10 weeks later. To further define the role of LMO3 in insulin-stimulated glucose uptake, insulin signaling, adipocyte bioenergetics, as well as endocrine function, experiments were conducted in 3T3-L1 adipocytes and newly differentiated human primary mature adipocytes, engineered for transient gain or loss of LMO3 expression, respectively. AAV transduction of eWAT results in strong and stable Lmo3 expression specifically in the adipocyte fraction over a course of 10 weeks with HFD feeding. LMO3 expression in eWAT significantly improved insulin sensitivity and healthy visceral adipose tissue expansion in diet-induced obesity, paralleled by increased serum adiponectin. In vitro, LMO3 expression in 3T3-L1 adipocytes increased PPARγ transcriptional activity, insulin-stimulated GLUT4 translocation and glucose uptake, as well as mitochondrial oxidative capacity in addition to fatty acid oxidation. Mechanistically, LMO3 induced the PPARγ coregulator Ncoa1, which was required for LMO3 to enhance glucose uptake and mitochondrial oxidative gene expression. In human mature adipocytes, LMO3 overexpression promoted, while silencing of LMO3 suppressed mitochondrial oxidative capacity. LMO3 expression in visceral adipose tissue regulates multiple genes that preserve adipose tissue functionality during obesity, such as glucose metabolism, insulin sensitivity, mitochondrial function, and adiponectin secretion. Together with increased PPARγ activity and Ncoa1 expression, these gene expression changes promote insulin-induced GLUT4 translocation, glucose uptake in addition to increased mitochondrial oxidative capacity, limiting HFD-induced adipose dysfunction. These data add LMO3 as a novel regulator improving visceral adipose tissue function during obesity. Key messages LMO3 increases beneficial visceral adipose tissue expansion and insulin sensitivity in vivo. LMO3 increases glucose uptake and oxidative mitochondrial activity in adipocytes. LMO3 increases nuclear coactivator 1 (Ncoa1). LMO3-enhanced glucose uptake and mitochondrial gene expression requires Ncoa1.

scholarly journals Adipose Tissue Remodeling in Children: The Link between Collagen Deposition and Age-Related Adipocyte Growth

2012 ◽  
Vol 97 (4) ◽  
pp. 1320-1327 ◽  
Author(s):  
Charmaine S. Tam ◽  
Joan Tordjman ◽  
Adeline Divoux ◽  
Louise A. Baur ◽  
Karine Clément
Keyword(s):  
Adipose Tissue ◽  
Tissue Remodeling ◽  
Collagen Deposition ◽  
Age Related ◽  
Adipose Tissue Remodeling
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