Effect of high FFA on glycogenolysis in oxidative rat hindlimb muscles during twitch stimulation

The effect of elevated free fatty acids (FFA) on carbohydrate (CHO) utilization in the oxidative muscles of the isolated hindlimb was determined using twitch contraction paradigms evoking a wide range of O2 uptakes and glycogenolysis. The hindlimb was perfused with either 0 or 1.8 mM FFA for 10 min at rest and then subjected to 20 min of stimulation at 0.4, 0.7, 1, 2, 3, or 4 Hz. Soleus (Sol), plantaris (Pl), and red gastrocnemius (RG) were sampled after rest perfusion or stimulation. FFA had little effect on glycogenolysis during stimulation, although glycogen sparing occurred with one of the lesser intensity protocols in each muscle (Sol, 0.4 Hz; RG, 0.7 Hz; Pl, 1 Hz). Muscle citrate and acetyl-CoA were elevated in Sol during several stimulation protocols with high FFA, but this effect was inconsistent in Pl and RG. The sparing of glycogen, when it did occur, was generally unrelated to increases in either citrate or acetyl-CoA content. Furthermore, protocols in which citrate or acetyl-CoA were elevated in the presence of elevated FFA did not demonstrate glycogen sparing. Hindlimb lactate efflux at rest was reduced with FFA but unaffected during stimulation. Glucose uptake was unaffected by FFA at rest and during stimulation protocols, except 3 Hz. The present study does not support the classically proposed roles of citrate and acetyl-CoA in the FFA-induced downregulation of CHO utilization in electrically stimulated rat skeletal muscle.

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Effects of fat availability on acetyl-CoA and acetylcarnitine metabolism in rat skeletal muscle

AJP Cell Physiology ◽

10.1152/ajpcell.1992.263.3.c653 ◽

1992 ◽

Vol 263 (3) ◽

pp. C653-C659 ◽

Cited By ~ 26

Author(s):

L. L. Spriet ◽

D. J. Dyck ◽

G. Cederblad ◽

E. Hultman

Keyword(s):

Skeletal Muscle ◽

Free Carnitine ◽

Fiber Types ◽

High Fat ◽

O2 Uptake ◽

Rat Skeletal Muscle ◽

Acetyl Coa ◽

Hindlimb Muscles ◽

Rest Perfusion ◽

Tetanic Tension

This study was designed to examine the effects of stimulation and fat availability on the contents of acetyl coenzyme A (acetyl-CoA), free CoA (CoASH), acetylcarnitine, and free carnitine in the oxidative fiber types of rat skeletal muscle. Hindlimb muscles were perfused with no exogenous free fatty acids (FFA) or high FFA (0.93 +/- 0.03 mM) for 10 min at rest and during isometric, tetanic stimulation. Soleus (SOL) and red gastrocnemius (RG) muscles were sampled prior to perfusion and following rest perfusion and 1 and 5 min of stimulation. The SOL muscle contains predominantly slow oxidative (SO) fibers and the RG contains 56% fast oxidative-glycolytic (FOG) and 35% SO fibers. O2 uptake and tetanic tension production were similar in the fat-free and high FFA treatments. Rest perfusion with high FFA increased acetyl-CoA from 14.6 +/- 1.0 to 20.1 +/- 2.5 nmol/g dry muscle (dm) and acetylcarnitine from 0.12 +/- 0.01 to 0.78 +/- 0.18 mumol/g dm in the RG, while fat-free perfusion had no effect. The SOL results were similar as high FFA increased acetyl-CoA from 7.7 +/- 1.0 to 14.2 +/- 3.1 nmol/g dm and acetylcarnitine from 0.14 +/- 0.02 to 0.49 +/- 0.09 mumol/g dm. Stimulation increased acetyl-CoA and acetylcarnitine to values above rest in SOL and RG in both treatments and removed all fat-free and high-fat differences. The decreases in CoASH and free carnitine were reciprocal to the increases in acetyl-CoA and acetylcarnitine at all time points in both muscles such that total CoA and carnitine were constant.(ABSTRACT TRUNCATED AT 250 WORDS)

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Persistent increase in glucose uptake by rat skeletal muscle following exercise

AJP Cell Physiology ◽

10.1152/ajpcell.1981.241.5.c200 ◽

1981 ◽

Vol 241 (5) ◽

pp. C200-C203 ◽

Cited By ~ 118

Author(s):

J. L. Ivy ◽

J. O. Holloszy

Keyword(s):

Skeletal Muscle ◽

Glucose Uptake ◽

Muscle Glycogen ◽

Glycogen Synthesis ◽

Exercise Stress ◽

Rat Skeletal Muscle ◽

Major Pathway ◽

Glycogen Accumulation ◽

Hindlimb Muscles ◽

Muscle Glycogen Concentration

The effect of a bout of exercise on glucose uptake and glycogen synthesis in skeletal muscle was examined using a perfused rat hindlimb preparation. Rats were subjected to a bout of swimming. The exercise stress was moderate as reflected in a reduction of muscle glycogen concentration of only 50%. Glucose uptake and glycogen synthesis were measured in perfused hindlimb muscles for a 30-min period beginning approximately 60 min following the exercise. The rate of glucose uptake in the absence of insulin was 10-fold higher in hindlimbs of exercised animals than in the controls. The rate of glucose uptake was also higher in exercised than in control muscles in the presence of 50 microunits/ml or 10 mU/ml of insulin, but these differences were smaller than that found in the absence of insulin. Conversion to glycogen was the major pathway for disposal of the glucose taken up by muscle. The rate of glycogen accumulation in the exercised plantaris muscles was greater than in the control muscles both in the absence and presence of insulin.

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Plasma Free Fatty Acids Decrease Insulin-Stimulated Skeletal Muscle Glucose Uptake by Suppressing Glycolysis in Conscious Rats

Diabetes ◽

10.2337/diab.45.4.446 ◽

1996 ◽

Vol 45 (4) ◽

pp. 446-453 ◽

Cited By ~ 46

Author(s):

J. K. Kim ◽

J. K. Wi ◽

J. H. Youn

Keyword(s):

Skeletal Muscle ◽

Fatty Acids ◽

Free Fatty Acids ◽

Glucose Uptake ◽

Plasma Free Fatty Acids ◽

Conscious Rats ◽

Skeletal Muscle Glucose Uptake

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Net substrates balance across hindlimb in conscious rabbit during late pregnancy

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1986.251.1.e42 ◽

1986 ◽

Vol 251 (1) ◽

pp. E42-E47 ◽

Cited By ~ 1

Author(s):

M. Bouisset ◽

M. C. Pere ◽

M. Gilbert

Keyword(s):

Skeletal Muscle ◽

Fatty Acids ◽

Free Fatty Acids ◽

Glucose Uptake ◽

Ketone Bodies ◽

Late Pregnancy ◽

Gravid Uterus ◽

Minor Importance ◽

Insulin Effect ◽

Increase Glucose Uptake

The present work performed in rabbits was designed to investigate whether changes in skeletal muscle metabolism could contribute to glucose homeostasis during late pregnancy a time at which there is a large glucose demand of the gravid uterus. We therefore studied the net substrate balance of glucose, lactate, free fatty acids, and ketone bodies across the hindlimb of pregnant animals (days 24 and 30) and virgin animals. Our data show that on day 24 the basal rate of glucose uptake is similar to that observed in virgin rabbits, but it decreases by approximately 60% on day 30 despite comparable levels of blood glucose and plasma insulin at both gestational ages. A moderate hyperglycemia (20% above basal level) and hyperinsulinemia (2- to 3-fold above basal level) sustained for 80 min failed to increase glucose uptake except in virgin animals. Estimates of the contribution of substrates to oxidative metabolism indicate that free fatty acids could represent the major fuel in all groups, whereas glucose would be of minor importance especially at term. It is concluded that in pregnancy a) under normoglycemia there is a reduced insulin effect on glucose uptake and b) under moderate hyperglycemia and hyperinsulinemia the insulin resistance results from an impaired stimulation of glucose uptake. Sparing glucose from the skeletal muscle, the mother can direct more glucose toward the uterus without marked increase in her production rate.

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Mutation yellow in agouti loci prevents age-related increase of skeletal muscle genes regulating free fatty acids oxidation

Vavilov Journal of Genetics and Breeding ◽

10.18699/vj18.358 ◽

2018 ◽

Vol 22 (2) ◽

pp. 265-272 ◽

Cited By ~ 1

Author(s):

Y. V. Piskunova ◽

A. Y. Kazantceva ◽

A. V. Baklanov ◽

N. M. Bazhan

Keyword(s):

Skeletal Muscle ◽

Fatty Acids ◽

Adipose Tissue ◽

Free Fatty Acids ◽

Glucose Uptake ◽

White Adipose Tissue ◽

Uncoupling Protein ◽

Age Related ◽

Brown Adipose ◽

Ay Mice

The lethal yellow mutation in agouti loci (Ay mutation) reduces the activity of melanocortin (MC) receptors and causes hyperphagia, obesity and type two diabetes mellitus in aging mice (Ay mice). It is unknown if changes in distinct elements of the metabolic system such as white adipose tissue (WAT) and brown adipose tissue (BAT), and skeletal muscle will manifest before the development of obesity. The aim of this work was to measure the relative gene expression of key proteins that regulate carbohydrate-lipid metabolism in WAT, BAT and skeletal muscle in Ay mice before the development of obesity. C57Bl/6J mice bearing a dominant autosomal mutation Ay (Ay /a mice) and mice of the standard genotype (a/a mice, control) have been studied in three age groups: 10, 15 and 30 weeks. The relative mRNA level of genes was measured by real-time PCR in skeletal muscles (uncoupling protein 3 (Ucp3) and carnitine palmitoyl transferase 1b (Cpt1b) (free fatty acids oxidation), solute carrier family 2 (facilitated glucose transporter), member 4 (Slc2a4) (glucose uptake)), in WAT lipoprotein lipase (Lpl) (triglyceride deposition), hormone-sensitive lipase (Lipe) (lipid mobilization), and Slc2a4 (glucose uptake)), and in BAT: uncoupling protein 1 (Ucp1) (energy expenditure). The expression of Cpt1b was reduced in young Ay mice (10 weeks), there was no transient peak of transcription of Cpt1b, Ucp3 in skeletal muscle tissue and Lipe, Slc2a4 in WAT in early adult Ay mice (15 weeks), which was noted in а/а mice. Reduction of the transcriptional activity of the studied genes in skeletal muscle and white adipose tissue can initiate the development of melanocortin obesity in Ay mice.

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