scholarly journals Metformin Inhibits Nuclear Receptor TR4-Mediated Hepatic Stearoyl-CoA Desaturase 1 Gene Expression With Altered Insulin Sensitivity

Diabetes ◽  
2011 ◽  
Vol 60 (5) ◽  
pp. 1493-1503 ◽  
Author(s):  
E. Kim ◽  
N.-C. Liu ◽  
I.-C. Yu ◽  
H.-Y. Lin ◽  
Y.-F. Lee ◽  
...  
Diabetes ◽  
1997 ◽  
Vol 46 (12) ◽  
pp. 2115-2118 ◽  
Author(s):  
S. Kurebayashi ◽  
T. Hirose ◽  
Y. Miyashita ◽  
S. Kasayama ◽  
T. Kishimoto

Author(s):  
Gabriel Wagner ◽  
Anna Fenzl ◽  
Josefine Lindroos-Christensen ◽  
Elisa Einwallner ◽  
Julia Husa ◽  
...  

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.


2008 ◽  
Vol 67 (OCE5) ◽  
Author(s):  
F. Respondek ◽  
K. Swanson ◽  
F. Herpigny ◽  
K. Belsito ◽  
B. Vester ◽  
...  

PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0159425 ◽  
Author(s):  
Yoon Seok Jung ◽  
Ji-Min Lee ◽  
Don-Kyu Kim ◽  
Yong-Soo Lee ◽  
Ki-Sun Kim ◽  
...  

2014 ◽  
Vol 11 (10) ◽  
pp. 10146-10164 ◽  
Author(s):  
Cinzia La Rocca ◽  
Sabrina Tait ◽  
Cristiana Guerranti ◽  
Luca Busani ◽  
Francesca Ciardo ◽  
...  

2007 ◽  
Vol 361 (2) ◽  
pp. 323-328 ◽  
Author(s):  
Eungseok Kim ◽  
Wen-Lung Ma ◽  
Din-Lii Lin ◽  
Shigeki Inui ◽  
Yuh-Ling Chen ◽  
...  

2011 ◽  
Vol 105 (8) ◽  
pp. 1226-1234 ◽  
Author(s):  
Nuria Granados ◽  
Jaume Amengual ◽  
Joan Ribot ◽  
Andreu Palou ◽  
M. Luisa Bonet

Trans-fatty acids (TFA) andcis-monounsaturated fat appear to exert detrimental and beneficial effects, respectively, on glucose metabolism and insulin sensitivity. Adipose tissue and skeletal muscle are a source of signalling proteins (adipokines and myokines), some of which have been related to the control of insulin sensitivity. Here, we investigated the possible differential effects of elaidic acid (EA;trans-9-18 : 1) – the major component in industrially produced TFA – and oleic acid (OA;cis-9-18 : 1) – itscis-isomer naturally present in food – on cellular glucose uptake and the expression of selected myokines and adipokines using cell models. Differentiated C2C12 myotubes and 3T3-L1 adipocytes were pretreated with the vehicle (control cells) or fatty acids for 24 h, after which basal and insulin-stimulated 2-deoxyglucose uptake and the expression of selected signalling proteins were measured. In C2C12 myotubes, pretreatment with OA, but not with EA, led to increased insulin-stimulated 2-deoxyglucose uptake and IL-6 expression levels, while pretreatment with EA, but not with OA, led to reduced IL-15 mRNA levels and increased TNF-α expression levels. In 3T3-L1 adipocytes, exposure to OA, but not to EA, resulted in reduced resistin gene expression and increased adiponectin gene expression. The results show evidence of distinct, direct effects of OA and EA on muscle glucose uptake and the expression of target myokines and adipokines, thus suggesting novel mechanisms by whichcis- andtrans-monounsaturated fat may differentially affect systemic functions.


Author(s):  
Ahmed El-Sayed ◽  
Ahmed Ateya ◽  
Mohamed Hamed ◽  
Sherif Shoieb ◽  
Hussam Ibrahim ◽  
...  

Objective: To assess the mRNA level of acetyl CoA carboxylase alpha (ACACA), fatty acid synthase (FASN), and stearoyl-CoA desaturase (SCD) by means of real-time PCR in Barki sheep subjected to complete feed deprivation. Design: Controlled study. Animals: Seven healthy pregnant ewes. Procedures: Ewes were subjected to complete feed deprivation with ad libitum water for five consecutive days. Venous blood samples were collected from each ewe before (zero time) and on the fifth day post-deprivation of feed for measurement of the mRNA level of ACACA, FASN, and SCD and assessment of serum metabolic profile parameters. Results: On the fifth day post-fasting, the gene expression pattern of ACACA, FASN, SCD genes showed a significant (p < 0.05) down regulation in comparison with pre-deprivation of feed. There was a significant (p < 0.05) increase in the serum level of non-esterified fatty acids (NEFA), beta-hydroxyl buteric acid (BHBA), and triglycerides in pregnant ewes in the fifth day post-fasting in comparison with pre-deprivation of feed. On the other hand, there was a significant (p < 0.05) decrease in the level of glucose, cholesterol, and insulin in pregnant ewes in the fifth day post-fasting compared with pre-deprivation of feed. On histopathology, liver showed marked heptic steatosis in midzonal and periportal area, with formation of small fatty cysts in liver lobule. There was a positive correlation between leptin and insulin (r = 0.996; p < 0.01), BHB and leptin (r = 0.951; p < 0.05) and glucose and SCD (r = 1.0, p < 0.01). However, there was a negative correlation between FASN and NEFA (r = - 0.991; p < 0.05), FASN and leptin (r = -0.683; p < 0.05) and FASN and cholesterol (r = - 0.82; p < 0.05). Conclusion and clinical relevance: Pregnant Barki ewes can clinically tolerate complete feed deprivation for five days, with down regulation of ACACA, FASN, SCD genes and presence of marked metabolic changes. Therefore, metabolic monitoring is warranted to predict the early changes associated with feed deprivation under different stressful conditions.


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