scholarly journals The Liver as the Site of Carnitine Biosynthesis in Sheep with Alloxan-induced Diabetes

1974 ◽  
Vol 27 (6) ◽  
pp. 645 ◽  
Author(s):  
AM Snoswell ◽  
GH Mclntosh

The total acid-soluble carnitine concentration in the livers of three sheep increased 20-fold, to 4530 nmoljg wet weight, 10-14 days after induction of the diabetic state by alloxan. There was a threefold increase in the total carnitine concentration of the kidney cortex and no significant change in that of heart or skeletal muscle (M. biceps femoris).

1972 ◽  
Vol 127 (1) ◽  
pp. 133-141 ◽  
Author(s):  
A. M. Snoswell ◽  
Patricia P. Koundakjian

1. The total acid-soluble carnitine concentrations of four tissues from Merino sheep showed a wide variation not reported for other species. The concentrations were 134, 538, 3510 and 12900nmol/g wet wt. for liver, kidney cortex, heart and skeletal muscle (M. biceps femoris) respectively. 2. The concentration of acetyl-CoA was approximately equal to the concentration of free CoA in all four tissues and the concentration of acid-soluble CoA (free CoA plus acetyl-CoA) decreased in the order liver>kidney cortex>heart>skeletal muscle. 3. The total amount of acid-soluble carnitine in skeletal muscle of lambs was 40% of that in the adult sheep, whereas the concentration of acid-soluble CoA was 2.5 times as much. A similar inverse relationship between carnitine and CoA concentrations was observed when different muscles in the adult sheep were compared. 4. Carnitine was confined to the cytosol in all four tissues examined, whereas CoA was equally distributed between the mitochondria and cytosol in liver, approx. 25% was present in the cytosol in kidney cortex and virtually none in this fraction in heart and skeletal muscle. 5. Carnitine acetyltransferase (EC 2.3.1.7) was confined to the mitochondria in all four tissues and at least 90% of the activity was latent. 6. Acetate thiokinase (EC 6.2.1.1) was predominantly (90%) present in the cytosol in liver, but less than 10% was present in this fraction in heart and skeletal muscle. 7. In alloxan-diabetes, the concentration of acetylcarnitine was increased in all four tissues examined, but the total acid-soluble carnitine concentration was increased sevenfold in the liver and twofold in kidney cortex. 8. The concentration of acetyl-CoA was approximately equal to that of free CoA in the four tissues of the alloxan diabetic sheep, but the concentration of acid-soluble CoA in liver increased approximately twofold in alloxan-diabetes. 9. The relationship between CoA and carnitine and the role of carnitine acetyltransferase in the various tissues is discussed. The quantitative importance of carnitine in ruminant metabolism is also emphasized.


1983 ◽  
Vol 61 (6) ◽  
pp. 328-332 ◽  
Author(s):  
Frank P. Bell ◽  
Anthony J. DeLucia

The level of carnitine and its esters was measured in plasma and liver in 20 male stump-tailed monkeys (Macaca arctoides) that were fed a moderately hypercholesterolemic diet. Plasma total carnitine was 60 ± 3 nmol/mL (30% esterified) and liver total carnitine was 254 ± 15 nmol/g wet weight (16% esterified) or 1.28 ± 0.07 nmol/mg noncollagen protein. The plasma concentration of total carnitine was positively correlated with the total carnitine concentration of the livers (r = 0.71, p < 0.001). Additionally, there was a positive correlation between plasma esterified carnitine and liver esterified carnitine (r = 0.92, p < 0.001) as well as between plasma esterified carnitine and plasma β-hydroxybutyrate (r = 0.92, p < 0.001), which together suggest that plasma esterified carnitine in the monkeys was largely of hepatic origin. There was no significant correlation between plasma carnitine (total, free, or esterified) and body mass, plasma triglycerides, or plasma cholesterol.


1975 ◽  
Vol 42 (3) ◽  
pp. 371-380 ◽  
Author(s):  
A. M. Snoswell ◽  
J. L. Linzell

SummaryTotal acid-soluble carnitine concentration in cow's, goat's and ewe's milk was 117, 101 and 872 nmol/ml respectively, of which acetylcarnitine made up 30% in goats, 10% in cows and 11% in ewes. The concentration of carnitine in the arterial blood of goats decreased significantly (P < 0·01) with the onset of lactation from 18·1 to 8·4nmol/ml and during lactation in goats and cows there was a significant arterio-venous difference of carnitine across the udder, with mean extractions of 14 and 5% respectively. Calculation of the udder uptake of carnitine, from these figures and from udder blood-flows, showed that in goats the amount lost in the milk was much less than that taken from the blood, but in cows about the same. Two groups of lactating ewes on low and high nutritional planes were sampled at 2-weekly intervals from 2 to 8 weeks of lactation. The concentrations of total acid-soluble carnitine and acetylcarnitine in the milk were similar in the 2 groups and remained relatively constant over this period, but the total acid-soluble carnitine concentration in jugular blood from the ewes on the low nutritional plane was significantly (P < 0·01) higher than from the ewes on the higher nutritional plane from the fourth week of lactation. The total acid-soluble carnitine concentration in liver of goats was 290 nmol/g wet wt; mammary gland, 324; kidney-cortex, 692; heart, 2030 and skeletal muscle, 14300. Carnitine acetyltransferase (E.C. 2.3.1.7) activity of mammary tissue from lactating ewes was 0·6 μmol per min per g wet wt of which approximately half appeared to be ‘latent’ or membrane bound. Acetate thiokinase (E.C. 6.2.1.1) activity in this tissue was found to be 1·5 μmol per min per g wet wt and was predominantly localized in the cytoplasm. Carnitine palmitoyltransferase (E.C. 2.3.1.21) activity in the same tissue was 0·8 μmol per min per g wet wt while no acetylcarnitine hydrolase activity could be detected. The results suggest that carnitine in mammary tissue is extracted from the blood for the oxidation of both acetate and long-chain fatty acids and that some is lost in the milk.


Author(s):  
Gertrud Angsten ◽  
Gitten Cederblad ◽  
Staffan Meurling

Background: We investigated muscle and plasma carnitine concentrations in children to establish reference intervals for use following biopsy of skeletal muscle. Methods: The study comprised 50 children from newborns up to 14 years of age, all undergoing elective surgery. They were divided into six age groups, the youngest 0-2 days and the oldest 11-14 years. The samples were taken at the beginning of surgery. Results: Gestational age was a major determinant of the total muscle carnitine concentration in newborns (Spearman's rs = 0·692, P < 0·01). This concentration was low during the first year, but subsequently did not differ between age groups. In neonates the median value (range) for total carnitine concentration in skeletal muscle was 5·9 (2·2-15·9) µmol/g dry weight and the free to total carnitine ratio was 62 (31-81)%. In children 1-12 months old the corresponding figures were 6·0 (3·5-7·9) µmol/g dry weight and 51 (28-71)% and in those 1-14 years they were 12·1 (6·6-17·4) µmol/g dry weight and 76 (42-92)%. Conclusion: This study shows that muscle carnitine concentrations in newborns are dependent on gestational age. The data suggest that there is an accretion of carnitine in skeletal muscle during the first year of life. Reference intervals are given.


1959 ◽  
Vol 197 (2) ◽  
pp. 491-493 ◽  
Author(s):  
A. D. Bender ◽  
D. D. Schottelius ◽  
B. A. Schottelius

Myoglobin concentration was determined in gastrocnemius and masseter muscles of guinea pigs maintained up to 15 days on vitamin E-deficient and vitamin E-supplemented diets. A statistically significant increase in myoglobin was noted in muscles of animals on the deficient diet for 15 days. That the increase was real and not apparent was attested by studies of total nitrogen, noncollagen nitrogen, percentage of solids and muscle wet weight, all of which were the same in control and experimental muscles. Histological sections and creatine excretion studies confirmed the impression of mild, incipient nutritional dystrophy.


2005 ◽  
Vol 61 (2) ◽  
Author(s):  
M. A. Gregory ◽  
M. N. Deane ◽  
M. Marsh

Objective: The precise mechanisms by which massage promotes repair in injured soft tissue are unknown. Various authorshave attributed the beneficial effects of massage to vasodilation and increased skin and muscle blood flow. The aim of this study was to determine whether deep transverse friction massage (DTF) causes capillary vasodilation in untraumatised skeletal muscle. Setting: Academic institution.Interventions: Twelve New Zealand white rabbits were anaesthetised and the left biceps femoris muscle received 10 minutes of DTF. Following treatment, wedge biopsies were taken from the musclewithin 10 minutes of treatment (R1 - 4), 24 hours (R5 - 8) and 6 days(R9 - 12) after treatment. To serve as controls, similar biopsies weretaken from the right biceps femoris of animals. The samples were fixed, dehydrated and embedded in epoxy resin.Transverse sections (1µm) of muscle were cut, stained with 1% aqueous alkaline toluidine blue and examined with a light microscope using a 40X objective. Images containing capillaries were captured using an image analyser with SIS software and the cross sectional diameters of at least 60 capillaries were measured from each specimen. Main Outcome Measures: Changes in capillary diameter. Results: The mean capillary diameters in control muscle averaged 4.76 µm. DTF caused a significant immediate increase of 17.3% in cross sectional area (p<0.001), which was not significantly increased by 10.0% after 24 hours (p>0.05). Six days after treatment the cross-sectional area of the treated muscle was 7.6% smaller than the controls. Conclusions: This confirms the contention that DTF stimulates muscle blood flow immediately after treatment and this may account for its beneficial effects in certain conditions. 


2020 ◽  
Vol 112 (2) ◽  
pp. 413-426 ◽  
Author(s):  
Carlijn M E Remie ◽  
Kay H M Roumans ◽  
Michiel P B Moonen ◽  
Niels J Connell ◽  
Bas Havekes ◽  
...  

ABSTRACT Background Nicotinamide riboside (NR) is an NAD+ precursor that boosts cellular NAD+ concentrations. Preclinical studies have shown profound metabolic health effects after NR supplementation. Objectives We aimed to investigate the effects of 6 wk NR supplementation on insulin sensitivity, mitochondrial function, and other metabolic health parameters in overweight and obese volunteers. Methods A randomized, double-blinded, placebo-controlled, crossover intervention study was conducted in 13 healthy overweight or obese men and women. Participants received 6 wk NR (1000 mg/d) and placebo supplementation, followed by broad metabolic phenotyping, including hyperinsulinemic-euglycemic clamps, magnetic resonance spectroscopy, muscle biopsies, and assessment of ex vivo mitochondrial function and in vivo energy metabolism. Results Markers of increased NAD+ synthesis—nicotinic acid adenine dinucleotide and methyl nicotinamide—were elevated in skeletal muscle after NR compared with placebo. NR increased body fat-free mass (62.65% ± 2.49% compared with 61.32% ± 2.58% in NR and placebo, respectively; change: 1.34% ± 0.50%, P = 0.02) and increased sleeping metabolic rate. Interestingly, acetylcarnitine concentrations in skeletal muscle were increased upon NR (4558 ± 749 compared with 3025 ± 316 pmol/mg dry weight in NR and placebo, respectively; change: 1533 ± 683 pmol/mg dry weight, P = 0.04) and the capacity to form acetylcarnitine upon exercise was higher in NR than in placebo (2.99 ± 0.30 compared with 2.40 ± 0.33 mmol/kg wet weight; change: 0.53 ± 0.21 mmol/kg wet weight, P = 0.01). However, no effects of NR were found on insulin sensitivity, mitochondrial function, hepatic and intramyocellular lipid accumulation, cardiac energy status, cardiac ejection fraction, ambulatory blood pressure, plasma markers of inflammation, or energy metabolism. Conclusions NR supplementation of 1000 mg/d for 6 wk in healthy overweight or obese men and women increased skeletal muscle NAD+ metabolites, affected skeletal muscle acetylcarnitine metabolism, and induced minor changes in body composition and sleeping metabolic rate. However, no other metabolic health effects were observed. This trial was registered at clinicaltrials.gov as NCT02835664


1988 ◽  
Vol 255 (3) ◽  
pp. R513-R519 ◽  
Author(s):  
G. P. Dobson ◽  
W. S. Parkhouse ◽  
J. M. Weber ◽  
E. Stuttard ◽  
J. Harman ◽  
...  

The aim of this study was to examine some metabolic properties and changes that occur in skeletal muscle and blood of greyhounds after an 800-m sprint. Three prime moving fast-twitch muscles were selected: biceps femoris (BF), gastrocnemius (G), and vastus lateralis (VL). The amount of glycogen utilized during the event was 42.57, 43.86, and 42.73 mumol glucosyl units/g wet wt, respectively. Expressed as a function of race time (48.3 +/- 0.7 s, n = 3), the mean rate of glycogen breakdown was 53.48 +/- 0.5 mumol.g wet wt-1.min-1 during the sprint. This is equivalent to an ATP turnover of 160 mumol.g wet wt-1.min-1, assuming 100% anaerobic conversion to lactate. This represents a conservative estimate, since greyhound muscle is heterogeneous and comprised of a large percentage of fast-twitch oxidative fibers (Armstrong et al., Am. J. Anat. 163: 87-98, 1982). The large decrease in muscle glycogen was accompanied by a 6- to 7-fold increase in muscle lactate from 3.48 +/- 0.13 to 25.42 +/- 3.54 (BF), 2.54 +/- 1.05 to 18.96 +/- 2.60 (G), and 4.57 +/- 0.44 to 30.09 +/- 1.94 mumol.g wet wt (VL), and a fall in muscle pH from 6.88 +/- 0.03 to 6.40 +/- 0.02 (BF), 6.92 +/- 0.02 to 6.56 +/- 0.02 (G), and 6.93 +/- 0.02 to 6.47 +/- 0.01 (VL). Cytosolic phosphorylation potential in BF decreased 10-fold from 11,360 +/- 680 to 1,184 +/- 347, and redox potential decreased 5-fold, indicating a marked reduction in the cytosol at this time.(ABSTRACT TRUNCATED AT 250 WORDS)


1960 ◽  
Vol 199 (2) ◽  
pp. 256-260 ◽  
Author(s):  
Joseph B. Boatman ◽  
Patricia A. Pisarcik ◽  
Marvin J. Rabinovitz

Liver, kidney and thyroid slices were taken from adult cats exposed to 0°C from 2 hours to 15 days, and incubated under oxygenation in Krebs-Ringer phosphate buffer media for 30 minutes at 38°C. Pre- and postincubation wet weight/dry weight and Na24 exchanges were measured. I131 exchange was measured in thyroid slices. At 1–12 hours of cold exposure kidney cortex, liver and thyroid exhibited increased uptake of water from the media, declining at 4–6 days of cold exposure below control values. By 8–12 days these values returned to control levels or above. Na24 uptake by kidney and liver slices and I131 uptake by thyroid was inversely proportional to values found for water uptake. I131 uptake by thyroid declined with time of cold exposure; by 8–12 days, I131 uptake from the media had significantly increased, reaching 45% above control values on the 15th day. It was concluded cold exposure placed severe and immediate metabolic demands upon the tissues, resulting in impaired tissue electrolyte and water equilibrium.


1982 ◽  
Vol 19 (6) ◽  
pp. 577-595 ◽  
Author(s):  
K. G. Braund ◽  
J. A. Mcguire ◽  
C. E. Lincoln

Cytochemical, histochemical, and morphometric features of skeletal muscle were evaluated in 140 specimens from five appendicular muscles of 28 dogs which were free of neuromuscular disease. Dogs ranged from six months to 15 years of age. Evidence of degeneration and regeneration, cell reactions and architectural change was found but with an incidence of less than 1% of the total myofiber population in any muscle. The number of fibers with internal nuclei never exceeded 1%. The only changes that appeared to be age-related were fiber size variation associated with the presence of small angular type IIA fibers in muscles of dogs seven years of age and older. Percentages of type I, type IIA, and type IIC fibers remained relatively constant in the various muscles in the age range examined. Type I fibers predominated in medial head of triceps brachii and superficial digital flexor muscles, whereas type IIA fibers were more numerous in biceps femoris and long head of triceps brachii muscles. An approximately equal ratio was found in gastrocranius muscles. In any given muscle, type IIC fibers represented less than 2% of the fibers. Statistically significant differences were found in values for fiber size between groups of dogs weighing more than (mean diameter range = 40 to 50 μm) and less than (mean diameter range = 30 to 40 μm) 15 kilograms.


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