scholarly journals Excess of Free Fatty Acids as a Cause of Metabolic Dysfunction in Skeletal Muscle

2016 ◽  
pp. 193-207 ◽  
Author(s):  
J. TUMOVA ◽  
M. ANDEL ◽  
J. TRNKA
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Muscle Metabolism ◽  
Dietary Lipids ◽  
Metabolic Dysfunction ◽  
Cellular Mechanisms ◽  
Peripheral Tissues ◽  
Cellular Dysfunction ◽  
The Impact

Obesity is often associated with metabolic impairments in peripheral tissues. Evidence suggests an excess of free fatty acids (FFA) as one factor linking obesity and related pathological conditions and the impact of FFA overload on skeletal muscle metabolism is described herein. Obesity is associated with dysfunctional adipose tissue unable to buffer the flux of dietary lipids. Resulting increased levels and fluxes of plasma FFA lead to ectopic lipid deposition and lipotoxicity. FFA accumulated in skeletal muscle are associated with insulin resistance and overall cellular dysfunction. Mechanisms supposed to be involved in these conditions include the Randle cycle, intracellular accumulation of lipid metabolites, inflammation and mitochondrial dysfunction or mitochondrial stress. These mechanisms are described and discussed in the view of current experimental evidence with an emphasis on conflicting theories of decreased vs. increased mitochondrial fat oxidation associated with lipid overload. Since different types of FFA may induce diverse metabolic responses in skeletal muscle cells, this review also focuses on cellular mechanisms underlying the different action of saturated and unsaturated FFA.

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.

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.

scholarly journals Omega-3 Polyunsaturated Fatty Acids: Benefits and Endpoints in Sport

Nutrients ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 46 ◽  
Author(s):  
Maria Gammone ◽  
Graziano Riccioni ◽  
Gaspare Parrinello ◽  
Nicolantonio D’Orazio
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Metabolic Response ◽  
Muscle Metabolism ◽  
Omega 3 ◽  
Cellular Functions ◽  
Inflammatory Conditions ◽  
Inflammatory Processes ◽  
And Performance

The influence of nutrition has the potential to substantially affect physical function and body metabolism. Particular attention has been focused on omega-3 polyunsaturated fatty acids (n-3 PUFAs), which can be found both in terrestrial features and in the marine world. They are responsible for numerous cellular functions, such as signaling, cell membrane fluidity, and structural maintenance. They also regulate the nervous system, blood pressure, hematic clotting, glucose tolerance, and inflammatory processes, which may be useful in all inflammatory conditions. Animal models and cell-based models show that n-3 PUFAs can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that they can influence not only the exercise and the metabolic response of skeletal muscle, but also the functional response for a period of exercise training. In addition, their potential anti-inflammatory and antioxidant activity may provide health benefits and performance improvement especially in those who practice physical activity, due to their increased reactive oxygen production. This review highlights the importance of n-3 PUFAs in our diet, which focuses on their potential healthy effects in sport.

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

035. Circadian rhythms and the early life programming of adult physiological systems

2005 ◽  
Vol 17 (9) ◽  
pp. 71
Author(s):  
D. J. Kennaway
Keyword(s):  
Circadian Rhythms ◽  
Neural Development ◽  
Optimal Time ◽  
Adult Health ◽  
Metabolic Dysfunction ◽  
Long Term Effects ◽  
Peripheral Tissues ◽  
Clock System ◽  
The Impact ◽  
Physiological Systems

We are all familiar with the idea that the external environment influences many diverse physiological systems. For example, the level of nutrition can not only influence adult health directly, but also fetal development and subsequently many adult functions in the offspring. Maternal stress can affect fetal outcomes as can the administration of drugs during pregnancy. Until recently, however, the daily changes in environmental light have been considered to really only influence the time that we sleep and in many other species the optimal time to mate. The impact of circadian rhythms on life trajectory has had little attention. In the last 5 years it has become clear that circadian rhythmicity is entrenched in virtually every cell of our bodies. A suite of clock gene transcription factors that include Clock, Bmal1 and the period and cryptochrome genes, generate a robust daily cycle of transcription and translation of hundreds of proteins. This cellular clock system is synchronised with the external photoperiod through retinal light perception, the hypothalamic suprachiasmatic nucleus (SCN) and neural and hormonal pathways. Most importantly when the clock system in peripheral tissues is disrupted, a growing list of detrimental consequences are being uncovered. As an example, mice with mutations in either Clock or Bmal1 have non-rhythmic peripheral tissues and exhibit mild to severe reproductive failure and metabolic dysfunction. Null per2 mice have a higher incidence of salivary gland hyperplasia, teratomas and increased susceptibility to radiation induced lymphomas. It is also apparent that intrauterine insults (e.g. cocaine administration, poor nutrition and stress) can have long term effects on the central circadian timing system in the SCN. Whether this involves alterations in neural development or gene function is not known. Nevertheless it is time we paid more attention to the temporal nature of our environment as a possible contributor to lifetime disorders and diseases.

scholarly journals Re-Setting the Circadian Clock Using Exercise against Sarcopenia

2020 ◽  
Vol 21 (9) ◽  
pp. 3106 ◽  
Author(s):  
Youngju Choi ◽  
Jinkyung Cho ◽  
Mi-Hyun No ◽  
Jun-Won Heo ◽  
Eun-Jeong Cho ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Intervention Strategy ◽  
Muscle Metabolism ◽  
Circadian Disruption ◽  
Adverse Health Outcomes ◽  
Exercise Timing ◽  
Underlying Mechanisms ◽  
The Impact

Sarcopenia is defined as the involuntary loss of skeletal muscle mass and function with aging and is associated with several adverse health outcomes. Recently, the disruption of regular circadian rhythms, due to shift work or nocturnal lifestyle, is emerging as a novel deleterious factor for the development of sarcopenia. The underlying mechanisms responsible for circadian disruption-induced sarcopenia include molecular circadian clock and mitochondrial function associated with the regulation of circadian rhythms. Exercise is a potent modulator of skeletal muscle metabolism and is considered to be a crucial preventative and therapeutic intervention strategy for sarcopenia. Moreover, emerging evidence shows that exercise, acting as a zeitgeber (time cue) of the skeletal muscle clock, can be an efficacious tool for re-setting the clock in sarcopenia. In this review, we provide the evidence of the impact of circadian disruption on skeletal muscle loss resulting in sarcopenia. Furthermore, we highlight the importance of exercise timing (i.e., scheduled physical activity) as a novel therapeutic strategy to target circadian disruption in skeletal muscle.

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