Carnitine-Palmitoyltransferase-1 Deficiency Impairs Skeletal Muscle Fatty Acid Oxidation, But Preserves Insulin Sensitivity

2012 ◽  
Vol 53 ◽  
pp. S99
Author(s):  
Shawna E. Wicks ◽  
Bolormaa Vandanmagsar ◽  
Kimberly R. Haynie ◽  
Jingying Zhang ◽  
Robert Noland ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Acid Oxidation ◽  
Carnitine Palmitoyltransferase ◽  
Acid Oxidation ◽  
Carnitine Palmitoyltransferase 1

scholarly journals Some aspects of fatty acid oxidation in isolated fat-cell mitochondria from rat

1975 ◽  
Vol 152 (3) ◽  
pp. 485-494 ◽  
Author(s):  
R D Harper ◽  
E D Saggerson
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Liver Mitochondria ◽  
Carnitine Palmitoyltransferase ◽  
Acid Oxidation ◽  
Fat Cells ◽  
Fat Cell ◽  
Carnitine Palmitoyltransferase Activity ◽  
Rate Limit ◽  
Carnitine Palmitoyltransferase 1

Mitochondrial were prepared from fat-cells isolated from rat epididymal adipose tissues of fed and 48 h-starved rats to study some aspects of fatty acid oxidation in this tissue. The data were compared with values obtained in parallel experiments with liver mitochondria that were prepared and incubated under identical conditions. 2. In the presence of malonate, fluorocitrate and arsenite, malate, but not pyruvate-bicarbonate, facilitated palmitoyl-group oxidation in both types of mitochondria. In the presence of malate, fat-cell mitochondria exhibited slightly higher rates of palmitoylcarnitine oxidation than liver. Rates of octanoylcarnitine oxidation were similar in liver and fat-cell mitochondria. Uncoupling stimulated acylcarnitine oxidation in liver, but not in fat-cell mitochondria. Oxidation of palmitoyl- and octanoyl-carnitine was partially additive in fat-cell but not in liver mitochondria. Starvation for 48 h significantly decreased both palmitoylcarnitine oxidation and latent carnitine palmitoyltransferase activity in fat-cell mitochondria. Starvation increased latent carnitine palmitoyltransferase activity in liver mitochondria but did not alter palmitoylcarnitine oxidation. These results suggested that palmitoylcarnitine oxidation in fat-cell but not in liver mitochondria may be limited by carnitine palmitoyltransferase 2 activity. 3. Fat-cell mitochondria also differed from liver mitochondria in exhibiting considerably lower rates of carnitine-dependent oxidation of palmitoyl-CoA or palmitate, suggesting that carnitine palmitoyltransferase 1 activity may severely rate-limit palmitoyl-CoA oxidation in adipose tissue.

scholarly journals High Incomplete Skeletal Muscle Fatty Acid Oxidation Explains Low Muscle Insulin Sensitivity in Poorly Controlled T2D

2017 ◽  
Vol 103 (3) ◽  
pp. 882-889 ◽  
Author(s):  
Timothy P Gavin ◽  
Jacob M Ernst ◽  
Hyo-Bum Kwak ◽  
Sarah E Caudill ◽  
Melissa A Reed ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Acid Oxidation ◽  
Mitochondrial Respiration ◽  
Vastus Lateralis ◽  
Acid Oxidation ◽  
Vastus Lateralis Muscle ◽  
Intravenous Glucose ◽  
Mitochondrial Respiratory

Abstract Context Almost 50% of type 2 diabetic (T2D) patients are poorly controlled [glycated hemoglobin (HbA1c) ≥ 7%]; however, the mechanisms responsible for progressively worsening glycemic control are poorly understood. Lower skeletal muscle mitochondrial respiratory capacity is associated with low insulin sensitivity and the development of T2D. Objective We investigated if skeletal muscle insulin sensitivity (SI) was different between well-controlled T2D (WCD) and poorly controlled T2D (PCD) and if the difference was associated with differences resulting from mitochondrial respiratory function. Design Vastus lateralis muscle mitochondrial respiration, mitochondrial content, mitochondrial enzyme activity, and fatty acid oxidation (FAO) were measured. SI and the acute response to glucose (AIRg) were calculated by MINMOD analysis from glucose and insulin obtained during a modified, frequently sampled, intravenous glucose tolerance test. Results SI and AIRg were lower in PCD than WCD. Muscle incomplete FAO was greater in PCD than WCD and greater incomplete FAO was associated with lower SI and higher HbA1c. Hydroxyacyl-coenzyme A dehydrogenase expression and activity were greater in PCD than WCD. There was no difference in maximal mitochondrial respiration or content between WCD and PCD. Conclusion The current results suggest that greater skeletal muscle incomplete FAO in poorly controlled T2D is due to elevated β oxidation and is associated with worsening muscle SI.

PGC-1α-induced improvements in skeletal muscle metabolism and insulin sensitivityThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 34 (3) ◽  
pp. 307-314 ◽  
Author(s):  
Arend Bonen
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Acid Oxidation ◽  
Insulin Signalling ◽  
Metabolic Effects ◽  
Zucker Rats ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Exercise Induced

The peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α), a nuclear encoded transcriptional coactivator, increases the expression of many genes in skeletal muscle, including those involved with fatty acid oxidation and oxidative phosphorylation. Exercise increases the expression of PGC-1α, and the exercise-induced upregulation of many genes is attributable, in part, to the preceding activation and upregulation of PGC-1α. Indeed, PGC-1α overexpression, like exercise training, increases exercise performance. PGC-1α reductions in humans have been observed in type 2 diabetes, while, in cell lines, PGC-1α mimics the exercise-induced improvement in insulin sensitivity. However, unexpectedly, in mammalian muscle, PGC-1α overexpression contributed to the development of diet-induced insulin resistance. This may have been related to the massive overexpression of PGC-1α, which induced the upregulation of the fatty acid transporter FAT/CD36 and led to an increase in intramuscular lipids, which interfere with insulin signalling. In contrast, when PGC-1α was overexpressed modestly, within physiological limits, mitochondrial fatty acid oxidation was increased, GLUT4 expression was upregulated, and insulin-stimulated glucose transport was increased. More recently, similar PGC-1α-induced improvements in the insulin-resistant skeletal muscle of obese Zucker rats have been observed. These studies suggest that massive PGC-1α overexpression, but not physiologic PGC-1α overexpression, induces deleterious metabolic effects, and that exercise-induced improvements in insulin sensitivity are induced, in part, by the exercise-induced upregulation of PGC-1α.

scholarly journals Genistein stimulates insulin sensitivity through gut microbiota reshaping and skeletal muscle AMPK activation in obese subjects

2020 ◽  
Vol 8 (1) ◽  
pp. e000948 ◽  
Author(s):  
Martha Guevara-Cruz ◽  
Einar T Godinez-Salas ◽  
Monica Sanchez-Tapia ◽  
Gonzalo Torres-Villalobos ◽  
Edgar Pichardo-Ontiveros ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Gut Microbiota ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Oral Glucose ◽  
Model Assessment ◽  
Metabolic Endotoxemia

ObjectiveObesity is associated with metabolic abnormalities, including insulin resistance and dyslipidemias. Previous studies demonstrated that genistein intake modifies the gut microbiota in mice by selectively increasing Akkermansia muciniphila, leading to reduction of metabolic endotoxemia and insulin sensitivity. However, it is not known whether the consumption of genistein in humans with obesity could modify the gut microbiota reducing the metabolic endotoxemia and insulin sensitivity.Research design and methods45 participants with a Homeostatic Model Assessment (HOMA) index greater than 2.5 and body mass indices of ≥30 and≤40 kg/m2 were studied. Patients were randomly distributed to consume (1) placebo treatment or (2) genistein capsules (50 mg/day) for 2 months. Blood samples were taken to evaluate glucose concentration, lipid profile and serum insulin. Insulin resistance was determined by means of the HOMA for insulin resistance (HOMA-IR) index and by an oral glucose tolerance test. After 2 months, the same variables were assessed including a serum metabolomic analysis, gut microbiota, and a skeletal muscle biopsy was obtained to study the gene expression of fatty acid oxidation.ResultsIn the present study, we show that the consumption of genistein for 2 months reduced insulin resistance in subjects with obesity, accompanied by a modification of the gut microbiota taxonomy, particularly by an increase in the Verrucomicrobia phylum. In addition, subjects showed a reduction in metabolic endotoxemia and an increase in 5′-adenosine monophosphate-activated protein kinase phosphorylation and expression of genes involved in fatty acid oxidation in skeletal muscle. As a result, there was an increase in circulating metabolites of β-oxidation and ω-oxidation, acyl-carnitines and ketone bodies.ConclusionsChange in the gut microbiota was accompanied by an improvement in insulin resistance and an increase in skeletal muscle fatty acid oxidation. Therefore, genistein could be used as a part of dietary strategies to control the abnormalities associated with obesity, particularly insulin resistance; however, long-term studies are needed.

scholarly journals AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice

Diabetologia ◽  
2014 ◽  
Vol 57 (8) ◽  
pp. 1693-1702 ◽  
Author(s):  
Hayley M. O’Neill ◽  
James S. Lally ◽  
Sandra Galic ◽  
Melissa Thomas ◽  
Paymon D. Azizi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Ampk Phosphorylation
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