Probing Insulin Sensitivity with Metabolically Competent Human Stem Cell‐Derived White Adipose Tissue Microphysiological Systems

Small ◽  
2021 ◽  
pp. 2103157
Author(s):  
Lin Qi ◽  
Peter‐James H. Zushin ◽  
Ching‐Fang Chang ◽  
Yue Tung Lee ◽  
Diana L. Alba ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Stem Cell ◽  
Insulin Sensitivity ◽  
White Adipose Tissue ◽  
Human Stem Cell ◽  
Microphysiological Systems

scholarly journals Central Leptin Regulates Total Ceramide Content and Sterol Regulatory Element Binding Protein-1C Proteolytic Maturation in Rat White Adipose Tissue

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 169-178 ◽  
Author(s):  
Elena Bonzón-Kulichenko ◽  
Dominik Schwudke ◽  
Nilda Gallardo ◽  
Eduardo Moltó ◽  
Teresa Fernández-Agulló ◽  
...  
Keyword(s):  
Nervous System ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
White Adipose Tissue ◽  
Binding Protein ◽  
Regulatory Element ◽  
Mrna Levels ◽  
Element Binding Protein ◽  
Ceramide Content ◽  
Sterol Regulatory Element

Obesity and type 2 diabetes are associated with insulin and leptin resistance, and increased ceramide contents in target tissues. Because the adipose tissue has become a central focus in these diseases, and leptin-induced increases in insulin sensitivity may be related to effects of leptin on lipid metabolism, we investigated herein whether central leptin was able to regulate total ceramide levels and the expression of enzymes involved in ceramide metabolism in rat white adipose tissue (WAT). After 7 d central leptin treatment, the total content of ceramides was analyzed by quantitative shotgun lipidomics mass spectrometry. The effects of leptin on the expression of several enzymes of the sphingolipid metabolism, sterol regulatory element binding protein (SREBP)-1c, and insulin-induced gene 1 (INSIG-1) in this tissue were studied. Total ceramide levels were also determined after surgical WAT denervation. Central leptin infusion significantly decreased both total ceramide content and the long-chain fatty acid ceramide species in WAT. Concomitant with these results, leptin decreased the mRNA levels of enzymes involved in de novo ceramide synthesis (SPT-1, LASS2, LASS4) and ceramide production from sphingomyelin (SMPD-1/2). The mRNA levels of enzymes of ceramide degradation (Asah1/2) and utilization (sphingomyelin synthase, ceramide kinase, glycosyl-ceramide synthase, GM3 synthase) were also down-regulated. Ceramide-lowering effects of central leptin were prevented by local autonomic nervous system denervation of WAT. Finally, central leptin treatment markedly increased INSIG-1 mRNA expression and impaired SREBP-1c activation in epididymal WAT. These observations indicate that in vivo central leptin, acting through the autonomic nervous system, regulates total ceramide levels and SREBP-1c proteolytic maturation in WAT, probably contributing to improve the overall insulin sensitivity. Central leptin decreases total ceramide levels and prevents sterol regulatory element binding protein (SREBP-1C) proteolytic maturation in white adipose tissue, and probably, in this way, contributes to improve the overall insulin sensitivity.

scholarly journals MicroRNA-181b Improves Glucose Homeostasis and Insulin Sensitivity by Regulating Endothelial Function in White Adipose Tissue

2016 ◽  
Vol 118 (5) ◽  
pp. 810-821 ◽  
Author(s):  
Xinghui Sun ◽  
Jibin Lin ◽  
Yu Zhang ◽  
Sona Kang ◽  
Nathan Belkin ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Endothelial Function ◽  
Glucose Homeostasis ◽  
White Adipose Tissue

Participation of ERα and ERβ in glucose homeostasis in skeletal muscle and white adipose tissue

2009 ◽  
Vol 297 (1) ◽  
pp. E124-E133 ◽  
Author(s):  
Rodrigo P. A. Barros ◽  
Chiara Gabbi ◽  
Andrea Morani ◽  
Margaret Warner ◽  
Jan-Åke Gustafsson
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
White Adipose Tissue ◽  
Glucose Transporter ◽  
Wild Type ◽  
Glut4 Expression ◽  
Glucose Challenge ◽  
Fasting Hypoglycemia

Glucose uptake and homeostasis are regulated mainly by skeletal muscle (SM), white adipose tissue (WAT), pancreas, and the liver. Participation of estradiol in this regulation is still under intense investigation. We have demonstrated that, in SM of male mice, expression of the insulin-regulated glucose transporter (GLUT)4 is reduced by estrogen receptor (ER)β agonists. In the present study, to investigate the relative contributions of ERα and ERβ in glucose homeostasis, we examined the effects of tamoxifen (Tam) on GLUT4 expression in SM and WAT in wild-type (WT) and ER−/− mice. ERβ−/− mice were characterized by fasting hypoglycemia, increased levels of SM GLUT4, pancreatic islet hypertrophy, and a belated rise in plasma insulin in response to a glucose challenge. ERα−/− mice, on the contrary, were hyperglycemic and glucose intolerant, and expression of SM GLUT4 was markedly lower than in WT mice. Tam had no effect on glucose tolerance or insulin sensitivity in WT mice. In ERα−/− mice, Tam increased GLUT4 and improved insulin sensitivity. i.e., it behaved as an ERβ antagonist in SM but had no effect on WAT. In ERβ−/− mice, Tam did not affect GLUT4 in SM but acted as an ERα antagonist in WAT, decreasing GLUT4. Thus, in the interplay between ERα and ERβ, ERβ-mediated repression of GLUT4 predominates in SM but ERα-mediated induction of GLUT4 predominates in WAT. This tissue-specific difference in dominance of one ER over the other is reflected in the ratio of the expression of the two receptors. ERα predominates in WAT and ERβ in SM.

scholarly journals Resistin expression and plasma concentration peak at different times during pregnancy in rats

2005 ◽  
Vol 185 (3) ◽  
pp. 551-559 ◽  
Author(s):  
Sergio Caja ◽  
Izaskun Martínez ◽  
María Abelenda ◽  
Marisa Puerta
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Plasma Concentration ◽  
White Adipose Tissue ◽  
Post Partum ◽  
Time Lag ◽  
Simultaneous Increase ◽  
Tissue Mass ◽  
Pregnant Rats ◽  
Adipose Tissue Mass

Resistin has been proposed as both an anti-adipogenic factor and an inducer of insulin resistance. During late pregnancy, white adipose tissue mass increases and insulin sensitivity decreases. To check for the involvement of resistin in these processes, we measured plasma resistin in pregnant and non-pregnant rats and in lactating dams. Plasma resistin increased by day 15 of pregnancy and remained high 5 days post partum. The simultaneous increase in plasma resistin concentration and the decrease in insulin sensitivity is compatible with resistin depressing maternal insulin sensitivity. Resistin expression increased 5–15 times in visceral white adipose tissue depots by day 8 of pregnancy but was similar to pre-pregnancy values by day 19. Resistin expression in the placenta and mammary gland was similar to that in the parametrial adipose depot by day 8 but was almost null by day 19. There was therefore a time-lag between the peaks in expression and in plasma concentration. White adipose tissue mass increased without changes in adipocyte size once peaks in resistin expression had passed, which is compatible with an anti-adipogenic role for enhanced resistin expression. A bolus injection of chorionic gonadotrophin – which peaks in early pregnancy – to non-pregnant rats increased resistin expression in white adipose tissue, indicating that this hormone is involved in controlling resistin expression. Resistin was not detected in cerebrospinal fluid. Our results have suggested a role for resistin in pregnancy.

scholarly journals Ectopic UCP1 Overexpression in White Adipose Tissue Improves Insulin Sensitivity in Lou/C Rats, a Model of Obesity Resistance

Diabetes ◽  
2015 ◽  
Vol 64 (11) ◽  
pp. 3700-3712 ◽  
Author(s):  
Anne-Laure Poher ◽  
Christelle Veyrat-Durebex ◽  
Jordi Altirriba ◽  
Xavier Montet ◽  
Didier J. Colin ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
White Adipose Tissue ◽  
Obesity Resistance

scholarly journals Markedly Reduced White Adipose Tissue and Increased Insulin Sensitivity in Adcyap1-Deficient Mice

2008 ◽  
Vol 107 (1) ◽  
pp. 41-48 ◽  
Author(s):  
Shuhei Tomimoto ◽  
Tatsuya Ojika ◽  
Norihito Shintani ◽  
Hitoshi Hashimoto ◽  
Ken-ichi Hamagami ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
White Adipose Tissue ◽  
Deficient Mice

Effect of dietary fat modification on subcutaneous white adipose tissue insulin sensitivity in patients with metabolic syndrome

2014 ◽  
Vol 58 (11) ◽  
pp. 2177-2188 ◽  
Author(s):  
Yolanda Jimenez-Gomez ◽  
Cristina Cruz-Teno ◽  
Oriol A. Rangel-Zuñiga ◽  
Juan R. Peinado ◽  
Pablo Perez-Martinez ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
White Adipose Tissue ◽  
Dietary Fat ◽  
Subcutaneous White Adipose Tissue

Effect of resistance training and garlic extract on insulin sensitivity/resistance and biochemical parameters in diabetic rats

2021 ◽  
pp. 1-8
Author(s):  
M. Shaker ◽  
G.R. Khamisipour ◽  
H. Sadeghipour ◽  
A. Zar ◽  
B. Naeimi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Resistance Training ◽  
Resistance Exercise ◽  
White Adipose Tissue ◽  
Cell Function ◽  
Uncoupling Protein ◽  
Diabetic Rats ◽  
Garlic Extract ◽  
Group D

Diabetes is one of the most important endocrine diseases in the world and obesity is one of the risk factors for this disease. The aim of this study was to evaluate the effect of a resistance exercise and garlic extract on insulin sensitivity/resistance and signal pathway of white adipose tissue to brown factors in diabetic rats. A total of 48 male Wistar rats weighing 180 to 250 g were divided into six groups (n=8): healthy control (C), diabetic control (D), diabetic with garlic extract at a dose of 50 mg/kg body weight (bw) (D+50), diabetic with garlic extract dose of 200 mg/kg bw (D+200), diabetic resistance training (D+Ex), and diabetic resistance training with garlic extract dose of 200 mg/kg bw (D+Ex+200). Plasma irisin levels in the D+200 and D+Ex groups, as well as the D+Ex+200 group showed a significant increase compared to the D group (P<0.001), while in the D+50 group no significant change was observed. Compared with group D, the expression of peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α gene was significantly increased in groups D+200 and D+Ex, as well as group D+Ex+200 (P<0.001). It can be said that resistance exercise with garlic extract is effective in controlling diabetes and reducing its complications. It also increases the expression of PGC-1α and uncoupling protein 1 genes in white adipose tissue and therefore has a positive effect on beta cell function by irisin.

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