Elevation of circulating free fatty acids abolishes down-regulation of skeletal muscle adiponectin receptor 1 (AdipoR1) expression caused by insulin infusion

2013 ◽  
Author(s):  
Marek Straczkowski ◽  
Monika Karczewska-Kupczewska ◽  
Agnieszka Adamska ◽  
Magdalena Stefanowicz ◽  
Natalia Matulewicz ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Insulin Infusion ◽  
Adiponectin Receptor ◽  
Down Regulation ◽  
Adiponectin Receptor 1

Exercise Training Improves Whole Body Insulin Resistance via Adiponectin Receptor 1

2015 ◽  
Vol 36 (13) ◽  
pp. e24-e30 ◽  
Author(s):  
J.-K. Cho ◽  
S.-U. Kim ◽  
H.-R. Hong ◽  
J.-H. Yoon ◽  
H.-S. Kang
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Dietary Treatment ◽  
Sirtuin 1 ◽  
Adiponectin Receptor ◽  
Whole Body ◽  
Peroxisome Proliferator ◽  
Down Regulation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Adiponectin Receptor 1

AbstractLittle is known regarding whether adiponectin receptors mediate high-intensity interval training (HIT)-induced improvement of insulin resistance associated with obesity. This study investigated the effect of HIT on whole body insulin resistance in high-fat diet-induced obese mice. 5-week-old male mice (N=30) were randomly assigned to standard chow (SC) (n=10) or HFD (n=20) for 23 weeks. After 15 weeks of dietary treatment, the HFD mice were further assigned to HFD (n=10) or HFD plus HIT (HFD+HIT, n=10). The HFD+HIT mice were subjected to HIT during the last 8 weeks of the 23-week HFD course. HFD resulted in whole body insulin resistance, hypoadiponectinemia, suppressed expression of adiponectin receptor 1(AdipoR1) and 2 (AdipoR2), suppressed expression of phosphorylated AMP-activated protein kinase (p-AMPK) and NAD-dependent deacetylase sirtuin-1 (SIRT1), and decreased mRNAs of peroxisome proliferator-activated receptor-α (PPARα), carnitine palmitoyltransferase I (CPT1), and acyl CoA oxidase (ACO) in skeletal muscle. In contrast, HIT alleviated whole body insulin resistance and prevented decreased levels of total adiponectin in both serum and adipose tissue. HIT also prevented the down-regulation of AdipoR1 and AMPK/SIRT1 proteins and the down-regulation of PPARα, CPT1, and ACO mRNAs. The current findings show that HIT alleviates whole body insulin resistance due to HFD-induced obesity via the AdipoR1 and AMPK/SIRT1 mediated-signaling pathway in skeletal muscle, implying the potential role of HIT to combat this metabolic condition.

Elevated plasma free fatty acids decrease basal protein synthesis, but not the anabolic effect of leucine, in skeletal muscle

2006 ◽  
Vol 291 (3) ◽  
pp. E666-E674 ◽  
Author(s):  
Charles H. Lang
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Protein Synthesis ◽  
Free Fatty Acids ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Short Term ◽  
Lipid Infusion ◽  
Igf I ◽  
Plasma Ffas

Elevations in free fatty acids (FFAs) impair glucose uptake in skeletal muscle. However, there is no information pertaining to the effect of elevated circulating lipids on either basal protein synthesis or the anabolic effects of leucine and insulin-like growth factor I (IGF-I). In chronically catheterized conscious rats, the short-term elevation of plasma FFAs by the 5-h infusion of heparin plus Intralipid decreased muscle protein synthesis by ∼25% under basal conditions. Lipid infusion was associated with a redistribution of eukaryotic initiation factor (eIF)4E from the active eIF4E·eIF4G complex to the inactive eIF4E·4E-BP1 complex. This shift was associated with a decreased phosphorylation of eIF4G but not 4E-BP1. Lipid infusion did not significantly alter either the total amount or phosphorylation state of mTOR, TSC2, S6K1, or the ribosomal protein S6 under basal conditions. In control rats, oral leucine increased muscle protein synthesis. This anabolic response was not impaired by lipid infusion, and no defects in signal transduction pathways regulating translation initiation were detected. In separate rats that received a bolus injection of IGF-I, lipid infusion attenuated the normal redistribution of eIF4E from the active to inactive complex and largely prevented the increased phosphorylation of 4E-BP1, eIF4G, S6K1, and S6. This IGF-I resistance was associated with enhanced Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1). These data indicate that the short-term elevation of plasma FFAs impairs basal protein synthesis in muscle by altering eIF4E availability, and this defect may be related to impaired phosphorylation of eIF4G, not 4E-BP1. Moreover, hyperlipidemia impairs IGF-I action but does not produce leucine resistance in skeletal muscle.

Rapid impairment of skeletal muscle glucose transport/phosphorylation by free fatty acids in humans

Diabetes ◽  
1999 ◽  
Vol 48 (2) ◽  
pp. 358-364 ◽  
Author(s):  
M. Roden ◽  
M. Krssak ◽  
H. Stingl ◽  
S. Gruber ◽  
A. Hofer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Glucose Transport ◽  
Muscle Glucose Transport

scholarly journals The ANGPTL3-4-8 model, a molecular mechanism for triglyceride trafficking

Open Biology ◽  
2016 ◽  
Vol 6 (4) ◽  
pp. 150272 ◽  
Author(s):  
Ren Zhang
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Free Fatty Acids ◽  
White Adipose Tissue ◽  
Skeletal Muscles ◽  
General Framework ◽  
Peripheral Tissues ◽  
Specific Regulation ◽  
Rate Limiting

Lipoprotein lipase (LPL) is a rate-limiting enzyme for hydrolysing circulating triglycerides (TG) into free fatty acids that are taken up by peripheral tissues. Postprandial LPL activity rises in white adipose tissue (WAT), but declines in the heart and skeletal muscle, thereby directing circulating TG to WAT for storage; the reverse is true during fasting. However, the mechanism for the tissue-specific regulation of LPL activity during the fed–fast cycle has been elusive. Recent identification of lipasin/angiopoietin-like 8 (Angptl8), a feeding-induced hepatokine, together with Angptl3 and Angptl4, provides intriguing, yet puzzling, insights, because all the three Angptl members are LPL inhibitors, and the deficiency (overexpression) of any one causes hypotriglyceridaemia (hypertriglyceridaemia). Then, why does nature need all of the three? Our recent data that Angptl8 negatively regulates LPL activity specifically in cardiac and skeletal muscles suggest an Angptl3-4-8 model: feeding induces Angptl8, activating the Angptl8–Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles, thereby making circulating TG available for uptake by WAT, in which LPL activity is elevated owing to diminished Angptl4; the reverse is true during fasting, which suppresses Angptl8 but induces Angptl4, thereby directing TG to muscles. The model suggests a general framework for how TG trafficking is regulated.

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