Exercise training decreases store-operated Ca2+entry associated with metabolic syndrome and coronary atherosclerosis

Edwards, James; Neeb, Zachary P.; Alloosh, Mouhamad; Long, Xin; Bratz, Ian N.; Peller, Cassandra R.; Byrd, James; Kumar, Sanjay; Obukhov, Alexander G.; Sturek, Michael

doi:10.1093/cvr/cvp308

Cited by 81 publications

(91 citation statements)

References 39 publications

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“…The Ossabaw swine model was selected for this study because of their thrifty genotype and their increased predisposition to the development of insulin resistance in response to high-fat/cholesterol and/or highfructose diets (1,7,8,21,27). It is difficult to investigate the early events associated with the development of insulin resistance in obese and/or type 2 diabetic humans.…”

Section: Discussionmentioning

confidence: 99%

“…For several years, Sturek's laboratory has used Ossabaw swine as a model to study the effect of diet-induced obesity on the development of insulin resistance, impaired glucose tolerance, dyslipidemia, metabolic syndrome (MS), nonalcoholic steatohepatitis, and cardiovascular complications (1,7,8,21,27). Swine fed hypercaloric diet high in fructose (MetS diet) develop MS defined by the presence of three or more of the risk factors, but not dyslipidemia, while high-fat/ cholesterol/fructose diet (DMetS diet) renders MS with the dyslipidemia component (21).…”

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confidence: 99%

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Effect of diet-induced obesity and metabolic syndrome on skeletal muscles of Ossabaw miniature swine

Clark

Alloosh

Wenzel

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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TY. Effect of diet-induced obesity and metabolic syndrome on skeletal muscles of Ossabaw miniature swine. Am J Physiol Endocrinol Metab 300: E848 -E857, 2011. First published February 8, 2011 doi:10.1152/ajpendo.00534.2010.-Ossabaw swine fed excess kilocalorie diet develop metabolic syndrome (MS) characterized by obesity, hypertension, insulin resistance, and glucose intolerance with/ without dyslipidemia. The purpose of this study was to test the hypothesis that MS would have a detrimental effect on skeletal muscle structure and cause changes in the expression of myosin heavy chains (MHCs). Adult male Ossabaw swine were fed for 24 wk highfructose or high-fat/cholesterol/fructose diets to induce normolipidemic MS (MetS) or dyslipidemic MS (DMetS), respectively, and were compared with the lean swine on control diet. MetS swine showed mild MS, lacking increases in total and low density lipoprotein (LDL) cholesterol, both of which were highly upregulated in DMetS swine. There was an ϳ1.2-fold increase in the cross-sectional areas of muscle fibers in MetS and DMetS groups compared with control for biceps femoris and plantaris muscles. In plantaris muscles, DMetS diet caused an ϳ2-fold decrease in slow MHC mRNA and protein expression and an ϳ1.2-to 1.8-fold increase in the number of intramyocellular lipid (IMCL) droplets without large changes in the size of the droplets. There was a trend to the decrease in slow MHC expression in muscles of swine on MetS diet. The number of IMCL droplets in muscle fibers of the MetS group was comparable to controls. These data correlate well with the data on total plasma cholesterol (control ϭ 60, MetS ϭ 70, and DMetS ϭ 298 mg/dl) and LDL (control ϭ 29, MetS ϭ 30, and DMetS ϭ 232 mg/dl). We conclude that structural changes observed in skeletal muscle of obese Ossabaw swine correlate with those previously reported for obese humans. obesity; fiber type composition; intramyocellular lipids; myosin heavy chains SKELETAL MUSCLE CONSTITUTES more than 40% of the total body weight and is one of the most important organs for glucose homeostasis. The mass and composition of skeletal muscle are critical for its functions. Obesity is a major risk factor for the development of both insulin resistance and noninsulin-dependent diabetes mellitus (NIDDM). Obesityrelated abnormalities lead to excessive accumulation of triglycerides and fatty acids in skeletal muscle fibers in the form of intramyocellular lipids (IMCL). IMCL accumulation is strongly associated with the impairment of glucose metabolism, oxidative stress, deficiency in energy production, insulin resistance, and eventually the development of type 2 diabetes (reviewed in Refs. 3 and 26).The fiber type composition of skeletal muscle has strong effects on metabolism and utilization of glucose and lipids. Lillioja et al. (22) showed that in vivo insulin action determined by the euglycemic clamp was positively correlated with the percentage of type 1 fibers and negatively correlated with the percentage of type 2b/x fibers in vastus lateralis ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Effect of diet-induced obesity and metabolic syndrome on skeletal muscles of Ossabaw miniature swine

Clark

Alloosh

Wenzel

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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“…Conversely, factors that inhibit TRPC channels are linked to protection against cardiovascular disease; they include nitric oxide, 61 pregnenolone sulphate, 56 dietary ω-3 fatty acids, 23 and exercise. 62 TRPC channels presumably did not evolve to enhance cardiovascular disease. Nevertheless, the emerging evidence suggests that there is particular importance in injury or inflammatory conditions.…”

Section: Association With Cardiovascular Disease Parametersmentioning

confidence: 99%

Characteristics of Transient Receptor Potential Canonical Calcium-Permeable Channels and Their Relevance to Vascular Physiology and Disease

Beech

2013

Circ J

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Transient receptor potential canonical (TRPC) proteins assemble to form ion channels that enable influx of calcium and sodium ions into cells. There are 6 TRPC proteins in humans but more TRPC channels may arise through heteromerization among TRPCs and other types of TRP protein. They are widely expressed and have multiple functions throughout the peripheral and central systems of the body. This review summarizes current knowledge of the characteristics of TRPC channels and discusses principles by which the channels operate. Modulators of the channels include lipids, redox factors, and agonists at G-protein and tyrosine kinase receptors. The channels enable coupling between these factors and the calcium ion, which is a master intracellular regulator of multiple cell functions. In the context of this information the review gives specific consideration to TRPC channels in vascular cells, which include endothelial cells, vascular smooth muscle cells, perivascular adipocytes, and cells of the hematopoietic lineage. It is discussed that the channels may have most significance as drivers of change when there is strain or insult in physiology or disease. The TRPC proteins constitute a substantial and important group of calcium-permeable channels. They remain enigmatic but there is increasing understanding of their properties and recognition of their importance in the vasculature as well as in other systems such as the myocardium. (Circ J 2013; 77: 570 -579)

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“…Calcium homeostasis is also affected and exposure of primary endothelial cells for 24-72 hours to high glucose also alters Store-Operated Ca 2+ Entry (SOCE) and has been associated with changes in expression of the Transient Receptor Potential Channel 1 (TRPC1) (Bishara and Ding, 2010). Comparable changes have been reported in the expression levels of TRPC1 and also another Store-Operated Ca 2+ Channel protein, STIM1, in the coronary artery of of the Ossabaw pig model of diabetes (Edwards et al, 2010). An increase in expression levels of TRPC1 has also been associated with vascular disease and injury thus suggesting that alterations in SOCE may be closely associated with the development of vascular disease and thus, potentially, another target for therapeutic intervention (Kumar et al, 2006;van Breemen et.…”

Section: Hyperglycaemia and Endothelial Dysfunctionmentioning

confidence: 99%

“…Nonetheless, as reflected in the Ossabaw pig colony on Ossabaw Island, (Georgia, USA) in as little as 500 years domestic pigs exposed to a feast and famine environment do become prone to the development of metabolic syndrome and diabetes when these feral pigs are provided the same diet as their domesticated cousins (Gerstein and Waltman, 2006;Whitfield 2003). Studies with Ossabaw pigs are providing insights into the pathophysiology of vascular disease associated with metabolic syndrome and diabetes (Edwards et al, 2010). The onehumped camel, Camelus dromedaries, is a desert animal that can withstand both a harsh climate and limited supplies of food and water, but, similar to the Ossabaw pig, when exposed to a high calorie diet develops signs of diabetes (Ali et al, 2006).…”

Section: What Can We Learn From Other Mammalian Species?mentioning

confidence: 99%

Glycaemic Control and Protection of the Vasculature from Glucose Toxicity

Ding¹,

Triggle²

2011

Medical Complications of Type 2 Diabetes

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Exercise training decreases store-operated Ca2+entry associated with metabolic syndrome and coronary atherosclerosis

Abstract: This is the first report of the protective effect of exercise on native CAD, peri-stent CAD, SOCE, and molecular expression of TRPC1, STIM1, and Orai1 in MetS.

Cited by 81 publications

References 39 publications

Effect of diet-induced obesity and metabolic syndrome on skeletal muscles of Ossabaw miniature swine

Effect of diet-induced obesity and metabolic syndrome on skeletal muscles of Ossabaw miniature swine

Characteristics of Transient Receptor Potential Canonical Calcium-Permeable Channels and Their Relevance to Vascular Physiology and Disease

Glycaemic Control and Protection of the Vasculature from Glucose Toxicity

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