Regulators of blood lipids and lipoproteins? PPARδ and AMPK, induced by exercise, are correlated with lipids and lipoproteins in overweight/obese men and women.

PPARδ is a transcription factor regulating the expression of genes involved in oxidative metabolism, which may regulate blood cholesterols through transcription of oxidative and lipoprotein metabolism genes. To determine the association of skeletal muscle PPARδ content with blood lipids and lipoproteins before and following exercise, overweight and obese men (n = 9) and women (n = 7) were recruited; age, BMI, body fat percentage, and Vo(2max) were (means ± SE) 45 ± 2.5 yr, 31.9 ± 1.4 kg/m(-2), 41.1 ± 1.5%, and 26.0 ± 1.3 mLO(2)·kg(-1)·min(-1), respectively. Subjects performed 12 wk of endurance exercise training (3 sessions/wk, progressing to 500 kcal/session). To assess the acute exercise response, subjects performed a single exercise session on a treadmill (70% Vo(2max), 400 kcal energy expenditure) before and after training. Muscle and blood samples were obtained prior to any exercise and 24 h after each acute exercise session. Muscle was analyzed for protein content of PPARδ, PPARα, PGC-1α, AMPKα, and the oxidative and lipoprotein markers FAT/CD36, CPT I, COX-IV, LPL, F(1) ATPase, ABCAI, and LDL receptor. Blood was assessed for lipids and lipoproteins. Repeated-measures ANOVA revealed no influence of sex on measured outcomes. PPARδ, PGC-1α, FAT/CD36, and LPL content were enhanced following acute exercise, whereas PPARα, AMPKα, CPT I, and COX-IV content were enhanced only after exercise training. PPARδ content negatively correlated with total and LDL cholesterol concentrations primarily in the untrained condition (r ≤ -0.4946, P < 0.05), whereas AMPKα was positively correlated with HDL cholesterol concentrations regardless of exercise (r ≥ 0.5543, P < 0.05). Our findings demonstrate exercise-induced expression of skeletal muscle PPARs and their target proteins, and this expression is associated with improved blood lipids and lipoproteins in obese adults.

[1]  S. Crouse,et al.  Acute Exercise and Training Alter Blood Lipid and Lipoprotein Profiles Differently in Overweight and Obese Men and Women , 2012, Obesity.

[2]  S. Crouse,et al.  VO2 Prediction and Cardiorespiratory Responses During Underwater Treadmill Exercise , 2011, Research quarterly for exercise and sport.

[3]  A. Bonen,et al.  Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle , 2010, The Journal of physiology.

[4]  H. Pilegaard,et al.  Endurance exercise induces mRNA expression of oxidative enzymes in human skeletal muscle late in recovery , 2010, Scandinavian journal of medicine & science in sports.

[5]  Stuart M Phillips,et al.  Acute {beta}-adrenergic stimulation does not alter mitochondrial protein synthesis or markers of mitochondrial biogenesis in adult men. , 2010, American journal of physiology. Regulatory, integrative and comparative physiology.

[6]  F. Toledo,et al.  Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity. , 2010, American journal of physiology. Endocrinology and metabolism.

[7]  S. Crouse,et al.  Comparative efficacy of water and land treadmill training for overweight or obese adults. , 2009, Medicine and science in sports and exercise.

[8]  B. Spiegelman,et al.  PPARδ Agonism Activates Fatty Acid Oxidation via PGC-1α but Does Not Increase Mitochondrial Gene Expression and Function , 2009, The Journal of Biological Chemistry.

[9]  M. Gibala,et al.  Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1alpha in human skeletal muscle. , 2009, Journal of applied physiology.

[10]  A. Bonen,et al.  Rapid exercise-induced changes in PGC-1alpha mRNA and protein in human skeletal muscle. , 2008, Journal of applied physiology.

[11]  A. Bonen,et al.  PGC-1alpha's relationship with skeletal muscle palmitate oxidation is not present with obesity despite maintained PGC-1alpha and PGC-1beta protein. , 2008, American journal of physiology. Endocrinology and metabolism.

[12]  Y. Hellsten,et al.  PGC-1α is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle , 2008 .

[13]  D. Muoio,et al.  Skeletal muscle adaptation to fatty acid depends on coordinated actions of the PPARs and PGC1 alpha: implications for metabolic disease. , 2007, Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme.

[14]  F. Schick,et al.  Role of AMP-activated protein kinase gamma 3 genetic variability in glucose and lipid metabolism in non-diabetic whites , 2007, Diabetologia.

[15]  J. Plutzky,et al.  PPARα in atherosclerosis and inflammation , 2007 .

[16]  N. Fujii,et al.  Skeletal Muscle Adaptation to Exercise Training , 2007, Diabetes.

[17]  R. Lai,et al.  Apolipoprotein A-I stimulates AMP-activated protein kinase and improves glucose metabolism , 2007, Diabetologia.

[18]  A. Krook,et al.  Role of AMP Kinase and PPARδ in the Regulation of Lipid and Glucose Metabolism in Human Skeletal Muscle* , 2007, Journal of Biological Chemistry.

[19]  Udo Hoffmann,et al.  Abdominal Visceral and Subcutaneous Adipose Tissue Compartments: Association With Metabolic Risk Factors in the Framingham Heart Study , 2007, Circulation.

[20]  B. Staels,et al.  Drug Insight: mechanisms of action and therapeutic applications for agonists of peroxisome proliferator-activated receptors , 2007, Nature Clinical Practice Endocrinology &Metabolism.

[21]  T. Willson,et al.  Triglyceride:High-Density Lipoprotein Cholesterol Effects in Healthy Subjects Administered a Peroxisome Proliferator Activated Receptor &dgr; Agonist , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[22]  J. Plutzky,et al.  PPARalpha in atherosclerosis and inflammation. , 2007, Biochimica et biophysica acta.

[23]  J. Shyy,et al.  Statins Activate AMP-Activated Protein Kinase In Vitro and In Vivo , 2006, Circulation.

[24]  B. Strotman,et al.  Nuclear translocation of EndoG at the initiation of disuse muscle atrophy and apoptosis is specific to myonuclei. , 2006, American journal of physiology. Regulatory, integrative and comparative physiology.

[25]  J. Zierath,et al.  Low‐intensity exercise increases skeletal muscle protein expression of PPARδ and UCP3 in type 2 diabetic patients , 2006, Diabetes/metabolism research and reviews.

[26]  R. Krauss,et al.  Endurance training has little effect on active muscle free fatty acid, lipoprotein cholesterol, or triglyceride net balances. , 2006, American journal of physiology. Endocrinology and metabolism.

[27]  T. Spector,et al.  AMP-kinase α2 subunit gene PRKAA2 variants are associated with total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol in normal women , 2006, Journal of Medical Genetics.

[28]  T. Kodama,et al.  Peroxisome proliferator-activated receptor δ (PPARδ), a novel target site for drug discovery in metabolic syndrome , 2006 .

[29]  R. DeFronzo,et al.  LKB1-AMPK signaling in muscle from obese insulin-resistant Zucker rats and effects of training. , 2006, American journal of physiology. Endocrinology and metabolism.

[30]  T. Kodama,et al.  Peroxisome proliferator-activated receptor delta (PPARdelta), a novel target site for drug discovery in metabolic syndrome. , 2006, Pharmacological research.

[31]  E. Taylor,et al.  Endurance training increases skeletal muscle LKB1 and PGC-1alpha protein abundance: effects of time and intensity. , 2005, American journal of physiology. Endocrinology and metabolism.

[32]  A. Russell,et al.  Mitofusins 1/2 and ERRα expression are increased in human skeletal muscle after physical exercise , 2005, The Journal of physiology.

[33]  P. Grandjean,et al.  Acute changes in blood lipids and enzymes in postmenopausal women after exercise. , 2005, Journal of applied physiology.

[34]  S. Luquet,et al.  Roles of PPAR delta in lipid absorption and metabolism: a new target for the treatment of type 2 diabetes. , 2005, Biochimica et biophysica acta.

[35]  C. Gumbs,et al.  Exercise Stimulates Pgc-1α Transcription in Skeletal Muscle through Activation of the p38 MAPK Pathway* , 2005, Journal of Biological Chemistry.

[36]  R. Evans,et al.  Regulation of Muscle Fiber Type and Running Endurance by PPARδ , 2004, PLoS biology.

[37]  B. Kemp,et al.  High-density lipoprotein and apolipoprotein AI increase endothelial NO synthase activity by protein association and multisite phosphorylation. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[38]  M J McKenna,et al.  Intensified exercise training does not alter AMPK signaling in human skeletal muscle. , 2004, American journal of physiology. Endocrinology and metabolism.

[39]  G. Muscat,et al.  The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells. , 2003, Molecular endocrinology.

[40]  Jourdan J. Pouliot,et al.  development and , 2019 .

[41]  G. Muscat,et al.  The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells. , 2003, Molecular endocrinology.

[42]  L. Nolte,et al.  Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC‐1 , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[43]  O. Pedersen,et al.  Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome. , 2002, Diabetes.

[44]  S. Kliewer,et al.  A selective peroxisome proliferator-activated receptor δ agonist promotes reverse cholesterol transport , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[45]  J. Horowitz,et al.  Effect of endurance training on lipid metabolism in women: a potential role for PPARalpha in the metabolic response to training. , 2000, American journal of physiology. Endocrinology and metabolism.

[46]  Paul Stevens Pipelines or Pipe Dreams? Lessons from the History of Arab Transit Pipelines , 2000 .

[47]  R. Pape Why Economic Sanctions Still Do Not Work , 1998, International Security.

[48]  R. Haass,et al.  Economic sanctions and American diplomacy , 1998 .

[49]  Antonio L. Furtado Islamic Republic of Iran : recent economic developments , 1998 .

[50]  Gary Clyde Hufbauer,et al.  US Economic Sanctions: Their Impact on Trade, Jobs, and Wages , 1997 .

[51]  R. Daumont Sudan : recent economic developments , 1997 .

[52]  P. Thompson,et al.  ACSM's Guidelines for Exercise Testing and Prescription , 1995 .

[53]  B. Kiens,et al.  Lipoprotein metabolism influenced by training-induced changes in human skeletal muscle. , 1989, The Journal of clinical investigation.

[54]  K. Vranizan,et al.  Assessment of habitual physical activity by a seven-day recall in a community survey and controlled experiments. , 1985, American journal of epidemiology.

[55]  P. K. Smith,et al.  Measurement of protein using bicinchoninic acid. , 1985, Analytical biochemistry.

[56]  Judith Gurney BP Statistical Review of World Energy , 1985 .

[57]  W. Evans,et al.  Suction applied to a muscle biopsy maximizes sample size. , 1982, Medicine and science in sports and exercise.

[58]  D. Costill,et al.  Calculation of percentage changes in volumes of blood, plasma, and red cells in dehydration. , 1974, Journal of applied physiology.

[59]  D. Hosmer,et al.  Maximal oxygen intake and nomographic assessment of functional aerobic impairment in cardiovascular disease. , 1973, American heart journal.

[60]  G. Borg Perceived exertion as an indicator of somatic stress. , 2019, Scandinavian journal of rehabilitation medicine.

[61]  J. Bergstrom MUSCLE ELECTROLYTES IN MAN DETERMINED BY NEUTRON ACTIVATION ANALYSIS ON NEEDLE BIOPSY SPECIMENS , 1962 .

[62]  L. Eriksen,et al.  The ether soluble porphyrins found in the urine of normal man and rabbit. , 1962, Scandinavian journal of clinical and laboratory investigation.