Effects of thyroid hormone administration on skeletal muscle mitochondria

The effects of thyroid hormone administration on the levels of a number of mitochondrial markers were measured in skeletal muscle and liver of normal rats. Injection of 18 mug of L-thyroxine (T4) per 100 g body wt every 4th day for 3 wk had no effect on the concentrations of cytochrome c, on citrate synthase activity, or on respiratory capacity of skeletal muscle. Injection of 200 mug of L-triiodothyronine (T3) daily for 5 days, or feeding 23 mg T4 and 7 mg T3/kg of diet for 2 wk, resulted in thyrotoxicosis and large increases in the activity of hepatic alpha-glycerophosphate dehydrogenase and other mitochondrial markers; however, the levels of activity of mitochondrial marker enzymes in gastrocnemius and quadriceps muscles were not significantly changed. Only when rats were fed 3 mg T4 and 1 mg T3/kg diet for a 6-wk period did we observe an increase in skeletal muscle mitochondrial markers. Thus, thyroxine treatment must be sufficiently prolonged if it is to be used as a tool for studying skeletal muscle mitochondrial biogenesis.

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Atorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affected

Scientific Reports ◽

10.1038/s41598-021-81846-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Liselotte Bruun Christiansen ◽

Tine Lovsø Dohlmann ◽

Trine Pagh Ludvigsen ◽

Ewa Parfieniuk ◽

Michal Ciborowski ◽

...

Keyword(s):

Skeletal Muscle ◽

Mitochondrial Function ◽

Citrate Synthase ◽

Obese Group ◽

Control Group ◽

Dependent Manner ◽

Respiratory Capacity ◽

Protein Carbonyl Content ◽

Functional Changes ◽

Mitochondrial Respiratory

AbstractStatins lower the risk of cardiovascular events but have been associated with mitochondrial functional changes in a tissue-dependent manner. We investigated tissue-specific modifications of mitochondrial function in liver, heart and skeletal muscle mediated by chronic statin therapy in a Göttingen Minipig model. We hypothesized that statins enhance the mitochondrial function in heart but impair skeletal muscle and liver mitochondria. Mitochondrial respiratory capacities, citrate synthase activity, coenzyme Q10 concentrations and protein carbonyl content (PCC) were analyzed in samples of liver, heart and skeletal muscle from three groups of Göttingen Minipigs: a lean control group (CON, n = 6), an obese group (HFD, n = 7) and an obese group treated with atorvastatin for 28 weeks (HFD + ATO, n = 7). Atorvastatin concentrations were analyzed in each of the three tissues and in plasma from the Göttingen Minipigs. In treated minipigs, atorvastatin was detected in the liver and in plasma. A significant reduction in complex I + II-supported mitochondrial respiratory capacity was seen in liver of HFD + ATO compared to HFD (P = 0.022). Opposite directed but insignificant modifications of mitochondrial respiratory capacity were seen in heart versus skeletal muscle in HFD + ATO compared to the HFD group. In heart muscle, the HFD + ATO had significantly higher PCC compared to the HFD group (P = 0.0323). In the HFD group relative to CON, liver mitochondrial respiration decreased whereas in skeletal muscle, respiration increased but these changes were insignificant when normalizing for mitochondrial content. Oral atorvastatin treatment in Göttingen Minipigs is associated with a reduced mitochondrial respiratory capacity in the liver that may be linked to increased content of atorvastatin in this organ.

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Differential modulation of expression of the two acylphosphatase isoenzymes by thyroid hormone

Biochemical Journal ◽

10.1042/bj3110567 ◽

1995 ◽

Vol 311 (2) ◽

pp. 567-573 ◽

Cited By ~ 6

Author(s):

P Chiarugi ◽

G Raugei ◽

R Marzocchini ◽

T Fiaschi ◽

C Ciccarelli ◽

...

Keyword(s):

Skeletal Muscle ◽

Thyroid Hormone ◽

State Level ◽

K562 Cells ◽

Hormone Treatment ◽

Differential Regulation ◽

Rapid Decrease ◽

Differential Modulation ◽

Hormone Administration ◽

Specific Mrna

The modulation of expression of the skeletal muscle and erythrocyte acylphosphatase isoenzymes by thyroid hormone has been investigated. Our results indicate a differential regulation of the two enzymic isoforms by tri-iodothyronine (T3) in K562 cells in culture: an increase in the specific mRNA during T3-stimulation is shown only for the skeletal muscle isoenzyme. A fast and transient T3 induction of the accumulation of the specific mRNA can be observed, reaching a maximum 8 h after hormone treatment and then rapidly decreasing almost to the steady-state level after 24 h. A nuclear run-on assay was performed to explore the mechanisms of this regulation. These studies indicate that T3 induction of skeletal muscle acylphosphatase mRNA is due, at least in part, to a fast and transient increase in the rate of gene transcription, within 4 h after hormone administration. A very rapid decrease is then observed within a further 2 h. T3-dependent accumulation of the mRNA for the skeletal muscle acylphosphatase requires ongoing protein synthesis, as confirmed by inhibition with cycloheximide or puromycin. These findings indicate that the transcriptional regulation of the gene may be indirect.

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241 Skeletal Muscle Mitochondrial Capacities Are Impacted by Breed and Temperament in Young Angus and Brahman Steers

Journal of Animal Science ◽

10.1093/jas/skab235.231 ◽

2021 ◽

Vol 99 (Supplement_3) ◽

pp. 127-127

Author(s):

Chloey P Guy ◽

Lauren T Wesolowski ◽

Audrey L Earnhardt ◽

Dustin Law ◽

Don A Neuendorff ◽

...

Keyword(s):

Skeletal Muscle ◽

Fixed Effects ◽

Linear Models ◽

Citrate Synthase ◽

Volume Density ◽

Skeletal Muscle Mitochondria ◽

Mitochondrial Volume ◽

Mitochondrial Volume Density ◽

Brahman Steers ◽

The Impact

Abstract Temperament impacts skeletal muscle mitochondria in Brahman heifers, but this has not been investigated in steers or between cattle breeds. We hypothesized mitochondrial measures would be greater in Angus than Brahman, temperamental than calm steers, and the trapezius (TRAP) than the longissimus thoracis (LT) muscle. Samples from calm (n = 13 per breed), intermediate (n = 12 per breed), and temperamental (n=13 per breed) Angus and Brahman steers (mean±SD 10.0±0.8 mo) were evaluated for mitochondrial enzyme activities via colorimetry. Calm and temperamental LT samples were evaluated for oxidative phosphorylation (P) and electron transfer (E) capacities by high-resolution respirometry. Data were analyzed using linear models with fixed effects of breed, muscle, temperament, and all interactions. Brahman tended to have greater mitochondrial volume density (citrate synthase activity; CS) than Angus (P = 0.08), while intrinsic (relative to CS) mitochondrial function (cytochrome c oxidase activity) was greater in Angus than Brahman (P = 0.001) and greater in TRAP than LT (P = 0.008). Angus exhibited greater integrative (per mg tissue) and intrinsic P with complex I (PCI), P with complexes I+II (PCI+II), maximum noncoupled E, and E with complex II (ECII; P ≤ 0.04) and tended to have greater intrinsic leak (P = 0.1) than Brahman. Contribution of PCI to total E was greater in Angus than Brahman (P = 0.01), while contribution of ECII to total E was greater in Brahman than Angus (P = 0.05). A trend for the interaction of breed and temperament (P = 0.07) indicated calm Angus had the greatest intrinsic ECII (P ≤ 0.03) while intrinsic ECII was similar between temperamental Angus and calm and temperamental Brahman. Integrative PCI+II and ECII, and the contribution of PCI and PCI+II to overall E tended to be greater in temperamental than calm steers (P ≤ 0.09), while intrinsic ECII tended to be greater in calm than temperamental steers (P = 0.07). The impact of these mitochondrial differences on meat quality measures remains to be determined.

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Influence of training on skeletal muscle enzymatic adaptations in normal and diabetic rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1985.249.4.e360 ◽

1985 ◽

Vol 249 (4) ◽

pp. E360-E365 ◽

Cited By ~ 2

Author(s):

E. G. Noble ◽

C. D. Ianuzzo

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Citrate Synthase ◽

Diabetic Rats ◽

Muscle Fiber Types ◽

Fiber Types ◽

Marker Enzymes ◽

Oxidative Potential ◽

Hydroxyacyl Coa Dehydrogenase ◽

Fast Twitch

Muscle homogenates representing slow-twitch oxidative, fast-twitch oxidative-glycolytic, fast-twitch glycolytic, and mixed fiber types were prepared from normal, diabetic, and insulin-treated diabetic rats. Diabetes was induced by injection of 80 mg . kg-1 of streptozotocin. The activities of citrate synthase, succinate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase were employed as markers of oxidative potential, whereas phosphorylase, hexokinase, and phosphofructokinase activities were used as an indication of glycolytic capacity. Diabetes was associated with a general decrement in the activity of oxidative marker enzymes for all fiber types except the fast-twitch glycolytic fiber. In contrast, the fast-twitch glycolytic fibers demonstrated the greatest decline in glycolytic enzymatic activity. Insulin-treated animals, either trained or untrained, exhibited enzyme activities similar to their normal counterparts. Exercise training of diabetic rats mimicked the effect of insulin treatment and caused a near normalization of the activity of the marker enzymes. These findings suggest that the enzymatic potential of all skeletal muscle fiber types of diabetic rats may be normalized by exercise training even in the absence of significant amounts of insulin.

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Sensitivity of Mitochondrial α-Glycerophosphate Dehydrogenase to Thyroid Hormone in Skeletal Muscle of the Rat

Hormone and Metabolic Research ◽

10.1055/s-0028-1095600 ◽

1976 ◽

Vol 8 (02) ◽

pp. 153-154 ◽

Cited By ~ 4

Author(s):

C. van Hardeveld ◽

R. Rusche ◽

A.A.H. Kassenaar

Keyword(s):

Skeletal Muscle ◽

Thyroid Hormone ◽

Glycerophosphate Dehydrogenase

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Response of mitochondria of different types of skeletal muscle to thyrotoxicosis

AJP Cell Physiology ◽

10.1152/ajpcell.1977.232.5.c180 ◽

1977 ◽

Vol 232 (5) ◽

pp. C180-C184 ◽

Cited By ~ 107

Author(s):

W. W. Winder ◽

J. O. Holloszy

Keyword(s):

Skeletal Muscle ◽

Citrate Synthase ◽

Differential Sensitivity ◽

Mitochondrial Enzymes ◽

Muscle Mitochondria ◽

Glycerophosphate Dehydrogenase ◽

Transport Chain ◽

Different Types ◽

Fast Twitch

To determine the effect of long-term thyrotoxicosis on muscle mitochondria, we measured representative mitochondrial enzymes from three different types of skeletal muscle (fast-twitch red and fast-twitch white from the quadriceps, and slow-twitch red from the soleus) in rats given 3 mg L-thyroxine and 1 mg triiodo-L-thyronine per kilogram of diet for 12 wk. Marker enzymes of the electron transport chain and citric acid cycle (cytochrome oxidase, cytochrome c, and citrate synthase) increase approximately twofold in soleus muscle in response to this treatment. The fast-twitch muscles exhibit no more than 44% increases in these enzymes in response to the same treatment. Relative to initial concentration, 3-hydroxybutyrate dehydrogenase increased to the same extent in fast-twitch red muscle as it did in the soleus (70%). Mitochondrial alpha-glycerophosphate dehydrogenase increased 76% in red quadriceps and 170% in soleus, but did not change in white muscle in the thyrotoxic rats. This differential sensitivity of the three types of muscle provides a tool for studying the mechanisms underlying the action of thyroid hormones on muscle mitochondria.

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Divergent skeletal muscle respiratory capacities in rats artificially selected for high and low running ability: a role for Nor1?

Journal of Applied Physiology ◽

10.1152/japplphysiol.00788.2012 ◽

2012 ◽

Vol 113 (9) ◽

pp. 1403-1412 ◽

Cited By ~ 27

Author(s):

Erin J. Stephenson ◽

Nigel K. Stepto ◽

Lauren G. Koch ◽

Steven L. Britton ◽

John A. Hawley

Keyword(s):

Skeletal Muscle ◽

Metabolic Regulation ◽

Citrate Synthase ◽

Uncoupling Protein ◽

Serum Insulin ◽

Orphan Receptor ◽

Western Society ◽

Orphan Nuclear Receptor ◽

Respiratory Capacity ◽

Relative Contribution

Inactivity-related diseases are becoming a huge burden on Western society. While there is a major environmental contribution to metabolic health, the intrinsic properties that predispose or protect against particular health traits are harder to define. We used rat models of inborn high running capacity (HCR) and low running capacity (LCR) to determine inherent differences in mitochondrial volume and function, hypothesizing that HCR rats would have greater skeletal muscle respiratory capacity due to an increase in mitochondrial number. Additionally, we sought to determine if there was a link between the expression of the orphan nuclear receptor neuron-derived orphan receptor (Nor)1, a regulator of oxidative metabolism, and inherent skeletal muscle respiratory capacity. LCR rats were 28% heavier ( P < 0.0001), and fasting serum insulin concentrations were 62% greater than in HCR rats ( P = 0.02). In contrast, HCR rats had better glucose tolerance and reduced adiposity. In the primarily oxidative soleus muscle, maximal respiratory capacity was 21% greater in HCR rats ( P = 0.001), for which the relative contribution of fat oxidation was 20% higher than in LCR rats ( P = 0.02). This was associated with increased citrate synthase (CS; 33%, P = 0.009) and β-hydroxyacyl-CoA (β-HAD; 33%, P = 0.0003) activities. In the primarily glycolytic extensor digitum longus muscle, CS activity was 29% greater ( P = 0.01) and β-HAD activity was 41% ( P = 0.0004) greater in HCR rats compared with LCR rats. Mitochondrial DNA copy numbers were also elevated in the extensor digitum longus muscles of HCR rats (35%, P = 0.049) and in soleus muscles (44%, P = 0.16). Additionally, HCR rats had increased protein expression of individual mitochondrial respiratory complexes, CS, and uncoupling protein 3 in both muscle types (all P < 0.05). In both muscles, Nor1 protein was greater in HCR rats compared with LCR rats ( P < 0.05). We propose that the differential expression of Nor1 may contribute to the differences in metabolic regulation between LCR and HCR phenotypes.

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Muscle respiratory capacity and VO2 max in identically trained young and old rats

Journal of Applied Physiology ◽

10.1152/jappl.1987.63.1.257 ◽

1987 ◽

Vol 63 (1) ◽

pp. 257-261 ◽

Cited By ~ 48

Author(s):

G. D. Cartee ◽

R. P. Farrar

Keyword(s):

Skeletal Muscle ◽

Citrate Synthase ◽

Treadmill Running ◽

Whole Body ◽

Vo2 Max ◽

Respiratory Enzymes ◽

Respiratory Capacity ◽

Palmitate Oxidation ◽

Age Related ◽

Old Rats

Old rats have a decreased hindlimb muscle respiratory capacity and whole-body maximal O2 consumption (VO2 max). The decline in spontaneous physical activity in old rats might contribute to these age-related changes. The magnitude of the age-related decline is not uniform in all skeletal muscle respiratory enzymes, and the decrease in palmitate oxidation is particularly great. This study was designed to determine if young and old rats subjected to the same exercise-training protocol would attain similar values for VO2 max and several markers of muscle respiratory capacity. Four- and 18-mo-old Fischer 344 rats underwent an identical 6-mo program of treadmill running. After training, both age groups had increased VO2 max above sedentary age-matched controls. However, the old trained rats had a lower VO2 max than identically trained young rats. In contrast to VO2 max, the two trained groups attained similar values for gastrocnemius citrate synthase, cytochrome oxidase, 3-hydroxyacyl-CoA dehydrogenase, palmitate oxidation, and total carnitine concentration. Thus, when the young and old rats performed an identical exercise protocol within the capacity of the old animals, differences in skeletal muscle respiratory capacity were eliminated. The dissimilarity in VO2 max between the identically trained groups was apparently caused by age-related differences in factors other than muscle respiratory capacity.

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Skeletal muscle respiratory capacity is enhanced in rats consuming an obesogenic Western diet

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00590.2011 ◽

2012 ◽

Vol 302 (12) ◽

pp. E1541-E1549 ◽

Cited By ~ 17

Author(s):

Erin J. Stephenson ◽

Donny M. Camera ◽

Trisha A. Jenkins ◽

Sepideh Kosari ◽

Jong Sam Lee ◽

...

Keyword(s):

Skeletal Muscle ◽

Energy Demand ◽

Citrate Synthase ◽

Blood Glucose Concentration ◽

Control Diet ◽

Fasting Blood Glucose ◽

Western Diet ◽

Mitochondrial Enzymes ◽

Serum Triglycerides ◽

Respiratory Capacity

Obesity-induced lipid oversupply promotes skeletal muscle mitochondrial biogenesis. Previous investigations have utilized extreme high-fat diets (HFD) to induce such mitochondrial perturbations despite their disparity from human obesogenic diets. Here, we evaluate the effects of Western diet (WD)-induced obesity on skeletal muscle mitochondrial function. Long-Evans rats were given ad libitum access to either a WD [40% energy (E) from fat, 17% protein, and 43% carbohydrate (30% sucrose); n = 12] or a control diet (CON; 16% of E from fat, 21% protein, and 63% carbohydrate; n = 12) for 12 wk. Rats fed the WD consumed 23% more E than CON ( P = 0.0001), which was associated with greater increases in body mass (23%, P = 0.0002) and adiposity (17%, P = 0.03). There were no differences in fasting blood glucose concentration or glucose tolerance between diets, although fasting insulin was increased by 40% ( P = 0.007). Fasting serum triglycerides were also elevated in WD (86%, P = 0.001). The maximal capacity of the electron transfer system was greater following WD (37%, P = 0.02), as were the maximal activities of several mitochondrial enzymes (citrate synthase, β-hydroxyacyl-CoA dehydrogenase, carnitine palmitoyltransferase). Protein expression of citrate synthase, UCP3, and individual respiratory complexes was greater after WD ( P < 0.05) despite no differences in the expression of peroxisome proliferator-activated receptor (PPAR)α, PPARδ, or PPARγ coactivator-1 mRNA or protein abundance. We conclude that the respiratory capacity of skeletal muscle is enhanced in response to the excess energy supplied by a WD. This is likely due to an increase in mitochondrial density, which at least in the short term, and in the absence of increased energy demand, may protect the tissue from lipid-induced impairments in glycemic control.

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