In obese rat muscle transport of palmitate is increased and is channeled to triacylglycerol storage despite an increase in mitochondrial palmitate oxidation

Holloway, Graham P.; Benton, Carley R.; Mullen, Kerry Lynn; Yoshida, Yuko; Snook, Laelie A.; Han, Xiaoxia; Glatz, Jan F. C.; Luiken, Joost J. F. P.; Lally, James; Dyck, David J.; Bonen, Arend

doi:10.1152/ajpendo.90896.2008

Cited by 92 publications

(156 citation statements)

References 49 publications

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“…The monoclonal antibody MO25 [14] was used to detect FAT. All other reagents were obtained from Sigma-Aldrich (St Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Protein isolation, activity and western blotting Muscles were homogenised and proteins separated using SDS-PAGE as previously described [3,14]. Equal quantities of protein were loaded for control and transfected muscles (confirmed with Ponceau S staining).…”

Section: Descriptive Characteristics Of Lean and Obese Zucker Ratsmentioning

confidence: 99%

“…Signals were detected using enhanced chemiluminescence (Perkin Elmer Life Science, Boston, MA, USA) and quantified by densitometry (SynGene, ChemiGenius2; Perkin-Elmer, Woodbridge, ON, Canada). Citrate synthase activity was measured in muscle homogenate [14].…”

Section: Descriptive Characteristics Of Lean and Obese Zucker Ratsmentioning

confidence: 99%

“…Excessive PGC-1α production induces many undesirable consequences, including abnormal mitochondrial proliferation, disruption of myofibrillar architecture, displacement of nuclei [12], obesity, intramuscular lipid accumulation and insulin resistance [10,11]. We [3,13] have suggested that insulin resistance in PGC-1α transgenic mice [10,11] may stem from a large, PGC-1α-induced increase in the fatty acid transporter, fatty acid translocase (FAT), which has been associated with increases in intramuscular lipids and insulin resistance in humans and in animals [14,15]. Viewed in this light, PGC-1α-induced insulin resistance in transgenic mice is less of a paradox than has been suggested [11].…”

Section: Introductionmentioning

confidence: 99%

“…Skeletal muscle insulin resistance can be examined in a model of high fat feeding [4] or in a genetically predisposed model such as obese Zucker rats [14]. Since insulin resistance is much greater in obese Zucker rats, we selected this more severe model to ascertain whether PGC-1α overproduction within physiological limits increased mitochondrial biogenesis, and improved mitochondrial fatty acid oxidation and insulin-stimulated glucose transport and signalling.…”

Section: Introductionmentioning

confidence: 99%

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Increased levels of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α) improve lipid utilisation, insulin signalling and glucose transport in skeletal muscle of lean and insulin-resistant obese Zucker rats

et al. 2010

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Aims/hypothesis Reductions in peroxisome proliferatoractivated receptor gamma, coactivator 1 alpha (PGC-1α) levels have been associated with the skeletal muscle insulin resistance. However, in vivo, the therapeutic potential of PGC-1α has met with failure, as supra-physiological overexpression of PGC-1α induced insulin resistance, due to fatty acid translocase (FAT)-mediated lipid accumulation. Based on physiological and metabolic considerations, we hypothesised that a modest increase in PGC-1α levels would limit FAT upregulation and improve lipid metabolism and insulin sensitivity, although these effects may differ in lean and insulin-resistant muscle. Methods Pgc-1α was transfected into lean and obese Zucker rat muscles. Two weeks later we examined mitochondrial biogenesis, intramuscular lipids (triacylglycerol, diacylglycerol, ceramide), GLUT4 and FAT levels, insulin-stimulated glucose transport and signalling protein phosphorylation (thymoma viral proto-oncogene 2 [Akt2], Akt substrate of 160 kDa [AS160]), and fatty acid oxidation in subsarcolemmal and intermyofibrillar mitochondria. Results Electrotransfection yielded physiologically relevant increases in Pgc-1α (also known as Ppargc1a) mRNA and protein (∼25%) in lean and obese muscle. This induced mitochondrial biogenesis, and increased FAT and GLUT4 levels, insulin-stimulated glucose transport, and Akt2 and AS160 phosphorylation in lean and obese animals, while bioactive intramuscular lipids were only reduced in obese muscle. Concurrently, PGC-1α increased palmitate oxidation in subsarcolemmal, but not in intermyofibrillar mitochondria, in both groups. In obese compared with lean animals, the PGC-1α-induced improvement in insulin-stimulated glucose transport was smaller, but intramuscular lipid reduction was greater. Conclusions/interpretations Increases in PGC-1α levels, similar to those that can be induced by physiological stimuli, altered intramuscular lipids and improved fatty acid oxidation, insulin signalling and insulin-stimulated glucose transport, albeit to different extents in lean and insulinresistant muscle. These positive effects are probably attributable to limiting the PGC-1α-induced increase in FAT, thereby preventing bioactive lipid accumulation as has occurred in transgenic PGC-1α animals.

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“…The monoclonal antibody MO25 [14] was used to detect FAT. All other reagents were obtained from Sigma-Aldrich (St Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

Section: Descriptive Characteristics Of Lean and Obese Zucker Ratsmentioning

confidence: 99%

Section: Descriptive Characteristics Of Lean and Obese Zucker Ratsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Increased levels of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α) improve lipid utilisation, insulin signalling and glucose transport in skeletal muscle of lean and insulin-resistant obese Zucker rats

et al. 2010

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In vivo multi‐tissue efficacy of peroxisome proliferator‐activated receptor‐γ therapy on glucose and fatty acid metabolism in obese type 2 diabetic rats

Nemanich

Rani

Shoghi

2013

Obesity

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ObjectiveTo identify the disturbances in glucose and lipid metabolism observed in Type 2 Diabetes Mellitus (T2DM), we examined the interaction and contribution of multiple tissues (liver, heart, muscle, and brown adipose tissue) and monitored the effects of the PPARγ agonist rosiglitazone (RGZ) on metabolism in these tissues.Design and MethodsRates of [18F]FDG and [11C]Palmitate uptake and utilization in the Zucker Diabetic Fatty (ZDF) rat were quantified using non-invasive positron emission tomography (PET) imaging and quantitative modeling in comparison to lean Zucker rats. Furthermore, we studied two separate groups of RGZ-treated and untreated ZDF ratsResultsGlucose uptake is impaired in ZDF brown fat, muscle, and heart tissues compared to leans, while RGZ treatment increased glucose uptake compared to untreated ZDF rats. Fatty acid (FA) uptake decreased, but FA flux increased in brown fat and skeletal muscle of ZDF rats. RGZ treatment increased uptake of FA in brown fat, but decreased uptake and utilization in liver, muscle and heart.ConclusionOur data indicate tissue-specific mechanisms for glucose and FA disposal as well a differential action of insulin-sensitizing drugs to normalize substrate handling and highlight the role that pre-clinical imaging may play in screening drugs for obesity and diabetes.

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Metabolic Syndrome is Associated with Ceramide Accumulation in Visceral Adipose Tissue of Women with Morbid Obesity

Choromańska

Myśliwiec

Hady

et al. 2019

Obesity

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Objective Accelerated transmembrane transport of long‐chain fatty acids dependent on fatty acid transporters is responsible for lipid accumulation and, eventually, the development of metabolic syndrome. This study determined the content of lipids (ceramide [CER], diacylglycerol [DAG], triacylglycerol, and free fatty acid [FFA]) and the expression of fatty acid translocase (FAT/CD36) and plasma membrane fatty acid‐binding protein in visceral adipose tissue (VAT) and subcutaneous adipose tissue of women with morbid obesity without metabolic syndrome (MetSx−) or with metabolic syndrome (MetSx+) and compared the results with those of lean controls without metabolic syndrome. Methods Lipid content and fatty acid composition in each lipid subclass were estimated by gas liquid chromatography. For total, plasma membrane, and mitochondrial expression of fatty acid transporters, subfractionation with subsequent Western blot technique was used. Results A greater content of triacylglycerol in VAT of participants with obesity (MetSx−) was found. However, only the MetSx+ subjects had increased content of CER in VAT in relation to subcutaneous adipose tissue in MetSx+ and lean individuals. This was accompanied by increased total and membrane expression of FAT/CD36 in VAT in MetSx+ subjects. Accordingly, mitochondrial expression of FAT/CD36 and plasma membrane fatty acid‐binding protein was decreased in both groups of subjects with obesity. Conclusions Metabolic syndrome is associated with the accumulation of CER in VAT, possibly related to increased FAT/CD36 protein expression.

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In obese rat muscle transport of palmitate is increased and is channeled to triacylglycerol storage despite an increase in mitochondrial palmitate oxidation

Abstract: In obese rat muscle transport of palmitate is increased and is channeled to triacylglycerol storage despite an increase in mitochondrial palmitate oxidation. Am J Physiol Endocrinol Metab 296: E738 -

Cited by 92 publications

References 49 publications

Increased levels of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α) improve lipid utilisation, insulin signalling and glucose transport in skeletal muscle of lean and insulin-resistant obese Zucker rats

Increased levels of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α) improve lipid utilisation, insulin signalling and glucose transport in skeletal muscle of lean and insulin-resistant obese Zucker rats

In vivo multi‐tissue efficacy of peroxisome proliferator‐activated receptor‐γ therapy on glucose and fatty acid metabolism in obese type 2 diabetic rats

Metabolic Syndrome is Associated with Ceramide Accumulation in Visceral Adipose Tissue of Women with Morbid Obesity

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