scholarly journals α-linolenic acid supplementation prevents exercise-induced improvements in white adipose tissue mitochondrial bioenergetics and whole-body glucose homeostasis in obese Zucker rats

Diabetologia ◽  
2017 ◽  
Vol 61 (2) ◽  
pp. 433-444 ◽  
Author(s):  
Cynthia M.F. Monaco ◽  
Ross Proudfoot ◽  
Paula M. Miotto ◽  
Eric A.F. Herbst ◽  
Rebecca E.K. MacPherson ◽  
...  
2018 ◽  
Vol 50 (8) ◽  
pp. 580-589
Author(s):  
Alex Rajna ◽  
Heather Gibling ◽  
Ousseynou Sarr ◽  
Sarthak Matravadia ◽  
Graham P. Holloway ◽  
...  

Evidence shows that proteins secreted from skeletal muscle influence a broad range of metabolic signaling pathways. We previously reported that essential polyunsaturated fatty acids (PUFA) improved whole-body glucose homeostasis in obese Zucker rats; however, the mechanisms underlying these benefits remain enigmatic. While PUFA and obesity influence skeletal muscle function, their effects on the secretome are unknown. The aim of this work was to determine if improvements in whole-body glucose homeostasis in obese Zucker rats fed diets supplemented with either linoleic acid (LA) or alpha-linolenic acid (ALA) for 12 wk are related to changes in the skeletal muscle secretome. Secreted proteins were identified with a predictive bioinformatic analysis of microarray gene expression from red tibialis anterior skeletal muscle. Approximately 130 genes were differentially expressed (false discovery rate = 0.05) in obese rats compared with lean controls. The expression of 15 genes encoding secreted proteins was differentially regulated in obese controls, obese LA-supplemented, and obese ALA-supplemented rats compared with lean controls. Five secreted proteins ( Col3a1, Col15a1, Pdgfd, Lyz2, and Angptl4) were differentially regulated by LA and ALA. Most notably, ALA supplementation reduced Angptl4 gene expression compared with obese control and obese-LA supplemented rats and reduced circulating ANGPTL4 serum concentrations. ALA also influenced Angptl4 gene expression and ANGPTL4 secretion from differentiated rat L6 myotubes. Altogether, the present data indicate that obesity has a greater global impact on skeletal muscle gene expression than either essential PUFA; however, LA and ALA may exert their metabolic benefits in part by regulating the skeletal muscle secretome.


1991 ◽  
Vol 279 (1) ◽  
pp. 303-308 ◽  
Author(s):  
L Pénicaud ◽  
P Ferré ◽  
F Assimacopoulos-Jeannet ◽  
D Perdereau ◽  
A Leturque ◽  
...  

Previous experiments have shown that insulin-induced glucose utilization is increased in white adipose tissue of young obese Zucker rats. We have investigated the possible role of over-expression of the muscle/fat glucose transporter (Glut 4) and key lipogenic enzymes in this increased insulin-responsiveness. The amount or activity and the mRNA concentrations of Glut 4, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) were measured before and after weaning in white adipose tissue of obese and lean Zucker rats. Comparison of the levels of Glut 4 and lipogenic-enzyme expression in 15-day-old suckling and 30-day-old weaned rats on a high-carbohydrate diet shows a marked increase in the latter group. The increase was, in lean and obese rats respectively, 6- and 7-fold for the amount of Glut 4 and 2- and 3-fold for its mRNA concentrations, 40- and 100-fold for the activity of lipogenic enzymes (FAS and ACC) and 30- and 10-fold for their mRNA concentrations. Furthermore, all these parameters, except the amount of Glut 4, were 2-5-fold higher in obese rats, both before and after weaning. Changes at weaning were largely blunted when rats were weaned on to a high-fat diet, although the differences between lean and obese rats persisted, and even became significant for the amount of Glut 4. Whatever the experimental conditions, plasma insulin levels were significantly higher in obese than in lean rats. These results indicate the existence of an enhanced expression of Glut 4, FAS and ACC in white adipose tissue of young obese fa/fa rats which could be related to the increased plasma insulin levels.


1988 ◽  
Vol 254 (3) ◽  
pp. E342-E348 ◽  
Author(s):  
S. Krief ◽  
R. Bazin ◽  
F. Dupuy ◽  
M. Lavau

In vivo whole-body glucose utilization and uptake in multiple individual tissues were investigated in conscious 30-day-old Zucker rats, which when obese are hyperphagic, hyperinsulinemic, and normoglycemic. Whole-body glucose metabolism (assessed by [3-3H]glucose) was 40% higher in obese (fa/fa) than in lean (Fa/fa) rats, suggesting that obese rats were quite responsive to their hyperinsulinemia (140 vs. 55 microU/ml). In obese compared with lean rats, tissue glucose uptake (assessed by the 2-deoxyglucose technique) was increased by 15, 12, and 6 times in dorsal, inguinal, perigonadal white depots, respectively; multiplied by 2.5 in brown adipose tissue; increased by 50% in skin from inguinal region but not in that from cranial, thoracic, or dorsal area; and increased twofold in diaphragm but similar in heart, in proximal intestine, and in total muscular mass of limbs. Our data establish that in young obese rats the hypertrophied white adipose tissue was a major glucose-utilizing tissue whose capacity for glucose disposal compared with that of half the muscular mass. Adipose tissue could therefore play an important role in the homeostasis of glucose in obese rats in the face of their increased carbohydrate intake.


2020 ◽  
Vol 7 ◽  
Author(s):  
Katarina Krskova ◽  
Lucia Balazova ◽  
Viktoria Dobrocsyova ◽  
Rafal Olszanecki ◽  
Maciej Suski ◽  
...  

The aim of our study was to determine the influence of inhibition of insulin-regulated aminopeptidase/oxytocinase (IRAP) on glucose tolerance and metabolism of skeletal muscle and visceral adipose tissue in obese Zucker rats. Obese Zucker rats administered with IRAP inhibitor–HFI-419 at a dose of 29 μg/100 g BW/day by osmotic minipumps implanted subcutaneously for 2 weeks. Two-hour intraperitoneal glucose tolerance test (ipGTT) was performed in fasting rats. Plasma oxytocin levels were measured by enzyme immunoassay after plasma extraction. In the musculus quadriceps and epididymal adipose tissue, the expression of factors affecting tissue oxidative status and metabolism was determined by real-time qPCR and/or Western blot analysys. The plasma and tissue enzymatic activities were determined by colorimetric or fluorometric method. Circulated oxytocin levels in obese animals strongly tended to increase after HFI-419 administration. This was accompanied by significantly improved glucose utilization during ipGTT and decreased area under the curve (AUC) for glucose. In skeletal muscle IRAP inhibitor treatment up-regulated enzymes of antioxidant defense system – superoxide dismutase 1 and 2 and improved insulin signal transduction pathway. HFI-419 increased skeletal muscle aminopeptidase A expression and activity and normalized its plasma levels in obese animals. In epididymal adipose tissue, gene expression of markers of inflammation and adipocyte hypertrophy was down-regulated in obese rats after HFI-419 treatment. Our results demonstrate that IRAP inhibition improves whole-body glucose tolerance in insulin-resistant Zucker fatty rats and that this metabolic effect of HFI-419 involves ameliorated redox balance in skeletal muscle.


2018 ◽  
Vol 62 (4) ◽  
pp. 1700606 ◽  
Author(s):  
Viviana Sandoval ◽  
Rosalía Rodríguez-Rodríguez ◽  
Úrsula Martínez-Garza ◽  
Cristina Rosell-Cardona ◽  
Rosa M. Lamuela-Raventós ◽  
...  

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