| 1. |
- Apró, William, et al.
(author)
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Resistance exercise induced mTORC1 signaling is not impaired by subsequent endurance exercise in human skeletal muscle.
- 2013
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In: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 305:1, s. E22-32
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Journal article (peer-reviewed)abstract
- The current dogma is that the muscle adaptation to resistance exercise is blunted when combined with endurance exercise. The suggested mechanism (based on rodent experiments) is that activation of adenosine monophosphate-activated protein kinase (AMPK) during endurance exercise impairs muscle growth through inhibition of the mechanistic target of rapamycin complex 1 (mTORC1). The purpose of this study was to investigate potential interference of endurance training on the signaling pathway of resistance training [mTORC1 phosphorylation of ribosomal protein S6 kinase 1 (S6K1)] in human muscle. Ten healthy and moderately trained male subjects performed on two separate occasions either acute high-intensity and high-volume resistance exercise (leg press, R) or R followed by 30 min of cycling (RE). Muscle biopsies were collected before and 1 and 3 h post resistance exercise. Phosphorylation of mTOR (Ser(2448)) increased 2-fold (P < 0.05) and that of S6K1 (Thr(389)) 14-fold (P < 0.05), with no difference between R and RE. Phosphorylation of eukaryotic elongation factor 2 (eEF2, Thr(56)) was reduced ∼70% during recovery in both trials (P < 0.05). An interesting finding was that phosphorylation of AMPK (Thr(172)) and acetyl-CoA carboxylase (ACC, Ser(79)) decreased ∼30% and ∼50%, respectively, 3 h postexercise (P < 0.05). Proliferator-activated receptor-γ coactivator-1 (PGC-1α) mRNA increased more after RE (6.5-fold) than after R (4-fold) (RE vs. R: P < 0.01) and was the only gene expressed differently between trials. These data show that the signaling of muscle growth through the mTORC1-S6K1 axis after heavy resistance exercise is not inhibited by subsequent endurance exercise. It is also suggested that prior activation of mTORC1 signaling may repress subsequent phosphorylation of AMPK.
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| 2. |
- Archer, A, et al.
(author)
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Skeletal muscle as a target of LXR agonist after long-term treatment: focus on lipid homeostasis
- 2014
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In: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 306:5, s. E494-E502
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Journal article (peer-reviewed)abstract
- The liver X receptors (LXR)α and LXRβ are transcription factors belonging to the nuclear receptor family, which play a central role in metabolic homeostasis, being master regulators of key target genes in the glucose and lipid pathways. Wild-type (WT), LXRα−/−, and LXRβ−/−mice were fed a chow diet with (treated) or without (control) the synthetic dual LXR agonist GW3965 for 5 wk. GW3965 raised intrahepatic triglyceride (TG) level but, surprisingly, reduced serum TG level through the activation of serum lipase activity. The serum TG reduction was associated with a repression of both catecholamine-stimulated lipolysis and relative glucose incorporation into lipid in isolated adipocytes through activation of LXRβ. We also demonstrated that LXRα is required for basal (nonstimulated) adipocyte metabolism, whereas LXRβ acts as a repressor of lipolysis. On the contrary, in skeletal muscle (SM), the lipogenic and cholesterol transporter LXR target genes were markedly induced in WT and LXRα−/−mice and to a lesser extent in LXRβ−/−mice following treatment with GW3965. Moreover, TG content was reduced in SM of LXRβ−/−mice, associated with increased expression of the main TG-lipase genes Hsl and Atgl. Energy expenditure was increased, and a switch from glucose to lipid oxidation was observed. In conclusion, we provide evidence that LXR might be an essential regulator of the lipid balance between tissues to ensure appropriate control of the flux of fuel. Importantly, we show that, after chronic treatment with GW3965, SM becomes the target tissue for LXR activation, as opposed to liver, in acute treatment.
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| 3. |
- Axling, Ulrika, et al.
(author)
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Rose hip exerts antidiabetic effects via a mechanism involving downregulation of the hepatic lipogenic program
- 2011
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In: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 300:1, s. 111-121
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Journal article (peer-reviewed)abstract
- Andersson U, Henriksson E, Strom K, Alenfall J, Goransson O, Holm C. Rose hip exerts antidiabetic effects via a mechanism involving downregulation of the hepatic lipogenic program. Am J Physiol Endocrinol Metab 300: E111-E121, 2011. First published October 19, 2010; doi:10.1152/ajpendo.00268.2010.-The aim of this study was to investigate the metabolic effects of a dietary supplement of powdered rose hip to C57BL/6J mice fed a high-fat diet (HFD). Two different study protocols were used; rose hip was fed together with HFD to lean mice for 20 wk (prevention study) and to obese mice for 10 wk (intervention study). Parameters related to obesity and glucose tolerance were monitored, and livers were examined for lipids and expression of genes and proteins related to lipid metabolism and gluconeogenesis. A supplement of rose hip was capable of both preventing and reversing the increase in body weight and body fat mass imposed by a HFD in the C57BL/6J mouse. Oral and intravenous glucose tolerance tests together with lower basal levels of insulin and glucose showed improved glucose tolerance in mice fed a supplement of rose hip compared with control mice. Hepatic lipid accumulation was reduced in mice fed rose hip compared with control, and the expression of lipogenic proteins was downregulated, whereas AMP-activated protein kinase and other proteins involved in fatty acid oxidation were unaltered. Rose hip intake lowered total plasma cholesterol as well as the low-density lipoprotein-to-high-density lipoprotein ratio via a mechanism not involving altered gene expression of sterol regulatory element-binding protein 2 or 3-hydroxymethylglutaryl-CoA reductase. Taken together, these data show that a dietary supplement of rose hip prevents the development of a diabetic state in the C57BL/6J mouse and that downregulation of the hepatic lipogenic program appears to be at least one mechanism underlying the antidiabetic effect of rose hip.
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| 4. |
- Benziane, B, et al.
(author)
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Effect of exercise and training on phospholemman phosphorylation in human skeletal muscle
- 2011
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In: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 301:3, s. E456-E466
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Journal article (peer-reviewed)abstract
- Phospholemman (PLM, FXYD1) is a partner protein and regulator of the Na+-K+-ATPase (Na+-K+pump). We explored the impact of acute and short-term training exercise on PLM physiology in human skeletal muscle. A group of moderately trained males ( n = 8) performed a 1-h acute bout of exercise by utilizing a one-legged cycling protocol. Muscle biopsies were taken from vastus lateralis at 0 and 63 min (non-exercised leg) and 30 and 60 min (exercised leg). In a group of sedentary males ( n = 9), we determined the effect of a 10-day intense aerobic cycle training on Na+-K+-ATPase subunit expression, PLM phosphorylation, and total PLM expression as well as PLM phosphorylation in response to acute exercise (1 h at ∼72% V̇o2peak). Biopsies were taken at rest, immediately following, and 3 h after an acute exercise bout before and at the conclusion of the 10-day training study. PLM phosphorylation was increased both at Ser63and Ser68immediately after acute exercise (75%, P < 0.05, and 30%, P < 0.05, respectively). Short-term training had no adaptive effect on PLM phosphorylation at Ser63and Ser68, nor was the total amount of PLM altered posttraining. The protein expressions of α1-, α2-,and β1-subunits of Na+-K+-ATPase were increased after training (113%, P < 0.05, 49%, P < 0.05, and 27%, P < 0.05, respectively). Whereas an acute bout of exercise increased the phosphorylation of PKCα/βII on Thr638/641pre- and posttraining, phosphorylation of PKCζ/λ on Thr403/410was increased in response to acute exercise only after the 10-day training. In conclusion, we show that only acute exercise, and not short-term training, increases phosphorylation of PLM on Ser63and Ser68, and data from one-legged cycling indicate that this effect of exercise on PLM phosphorylation is not due to systemic factors. Our results provide evidence that phosphorylation of PLM may play a role in the acute regulation of the Na+-K+-ATPase response to exercise.
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| 5. |
- Bishop, David J, et al.
(author)
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Sodium bicarbonate ingestion prior to training improves mitochondrial adaptations in rats.
- 2010
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In: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 299:2, s. E225-33
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Journal article (peer-reviewed)abstract
- We tested the hypothesis that reducing hydrogen ion accumulation during training would result in greater improvements in muscle oxidative capacity and time to exhaustion (TTE). Male Wistar rats were randomly assigned to one of three groups (CON, PLA, and BIC). CON served as a sedentary control, whereas PLA ingested water and BIC ingested sodium bicarbonate 30 min prior to every training session. Training consisted of seven to twelve 2-min intervals performed five times/wk for 5 wk. Following training, TTE was significantly greater in BIC (81.2 +/- 24.7 min) compared with PLA (53.5 +/- 30.4 min), and TTE for both groups was greater than CON (6.5 +/- 2.5 min). Fiber respiration was determined in the soleus (SOL) and extensor digitorum longus (EDL), with either pyruvate (Pyr) or palmitoyl carnitine (PC) as substrates. Compared with CON (14.3 +/- 2.6 nmol O(2).min(-1).mg dry wt(-1)), there was a significantly greater SOL-Pyr state 3 respiration in both PLA (19.6 +/- 3.0 nmol O(2).min(-1).mg dry wt(-1)) and BIC (24.4 +/- 2.8 nmol O(2).min(-1).mg dry wt(-1)), with a significantly greater value in BIC. However, state 3 respiration was significantly lower in the EDL from both trained groups compared with CON. These differences remained significant in the SOL, but not the EDL, when respiration was corrected for citrate synthase activity (an indicator of mitochondrial mass). These novel findings suggest that reducing muscle hydrogen ion accumulation during running training is associated with greater improvements in both mitochondrial mass and mitochondrial respiration in the soleus.
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| 6. |
- Boon, Hanneke, 1981-, et al.
(author)
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Influence of chronic and acute spinal cord injury on skeletal muscle Na+-K+-ATPase and phospholemman expression in humans
- 2012
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In: American Journal of Physiology. Endocrinology and Metabolism. - Bethesda, MD : American Physiological Society. - 0193-1849 .- 1522-1555. ; 302:7, s. E864-E871
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Journal article (peer-reviewed)abstract
- Na +-K +-ATPase is an integral membrane protein crucial for the maintenance of ion homeostasis and skeletal muscle contractibility. Skeletal muscle Na +-K +-ATPase content displays remarkable plasticity in response to long-term increase in physiological demand, such as exercise training. However, the adaptations in Na +-K +-ATPase function in response to a suddenly decreased and/or habitually low level of physical activity, especially after a spinal cord injury (SCI), are incompletely known. We tested the hypothesis that skeletal muscle content of Na +-K +-ATPase and the associated regulatory proteins from the FXYD family is altered in SCI patients in a manner dependent on the severity of the spinal cord lesion and postinjury level of physical activity. Three different groups were studied: 1) six subjects with chronic complete cervical SCI, 2) seven subjects with acute, complete cervical SCI, and 3) six subjects with acute, incomplete cervical SCI. The individuals in groups 2 and 3 were studied at months 1, 3, and 12 postinjury, whereas individuals with chronic SCI were compared with an able-bodied control group. Chronic complete SCI was associated with a marked decrease in [ 3H]ouabain binding site concentration in skeletal muscle as well as reduced protein content of the α 1-, α 1-, and (β1-subunit of the Na +-K +-ATPase. In line with this finding, expression of the Na +-K +-ATPase α 1-, α 1- subunits progressively decreased during the first year after complete but not after incomplete SCI. The expression of the regulatory protein phospholemman (PLM or FXYD1) was attenuated after complete, but not incomplete, cervical SCI. In contrast, FXYD5 was substantially upregulated in patients with complete SCI. In conclusion, the severity of the spinal cord lesion and the level of postinjury physical activity in patients with SCI are important factors controlling the expression of Na +-K +-ATPase and its regulatory proteins PLM and FXYD5. © 2012 the American Physiological Society.
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| 7. |
- Borgenvik, Marcus, et al.
(author)
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Intake of branched-chain amino acids influences the levels of MAFbx mRNA and MuRF-1 total protein in resting and exercising human muscle.
- 2012
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In: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 302:5, s. E510-21
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Journal article (peer-reviewed)abstract
- Resistance exercise and amino acids are two major factors that influence muscle protein turnover. Here, we examined the effects of resistance exercise and branched-chain amino acids (BCAA), individually and in combination, on the expression of anabolic and catabolic genes in human skeletal muscle. Seven subjects performed two sessions of unilateral leg press exercise with randomized supplementation with BCAA or flavored water. Biopsies were collected from the vastus lateralis muscle of both the resting and exercising legs before and repeatedly after exercise to determine levels of mRNA, protein phosphorylation, and amino acid concentrations. Intake of BCAA reduced (P < 0.05) MAFbx mRNA by 30 and 50% in the resting and exercising legs, respectively. The level of MuRF-1 mRNA was elevated (P < 0.05) in the exercising leg two- and threefold under the placebo and BCAA conditions, respectively, whereas MuRF-1 total protein increased by 20% (P < 0.05) only in the placebo condition. Phosphorylation of p70(S6k) increased to a larger extent (∼2-fold; P < 0.05) in the early recovery period with BCAA supplementation, whereas the expression of genes regulating mTOR activity was not influenced by BCAA. Muscle levels of phenylalanine and tyrosine were reduced (13-17%) throughout recovery (P < 0.05) in the placebo condition and to a greater extent (32-43%; P < 0.05) following BCAA supplementation in both resting and exercising muscle. In conclusion, BCAA ingestion reduced MAFbx mRNA and prevented the exercise-induced increase in MuRF-1 total protein in both resting and exercising leg. Further-more, resistance exercise differently influenced MAFbx and MuRF-1 mRNA expression, suggesting both common and divergent regulation of these two ubiquitin ligases.
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| 8. |
- Borjesson, AE, et al.
(author)
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The role of estrogen receptor-α and its activation function-1 for growth plate closure in female mice
- 2012
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In: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 302:11, s. E1381-E1389
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Journal article (peer-reviewed)abstract
- High estradiol levels in late puberty induce growth plate closure and thereby cessation of growth in humans. In mice, the growth plates do not fuse after sexual maturation, but old mice display reduced longitudinal bone growth and high-dose estradiol treatment induces growth plate closure. Estrogen receptor (ER)-α stimulates gene transcription via two activation functions (AFs), AF-1 and AF-2. To evaluate the role of ERα and its AF-1 for age-dependent reduction in longitudinal bone growth and growth plate closure, female mice with inactivation of ERα (ERα−/−) or ERαAF-1 (ERαAF-10) were evaluated. Old (16- to 19-mo-old) female ERα−/−mice showed continued substantial longitudinal bone growth, resulting in longer bones (tibia: +8.3%, P < 0.01) associated with increased growth plate height (+18%, P < 0.05) compared with wild-type (WT) mice. In contrast, the longitudinal bone growth ceased in old ERαAF-10mice (tibia: −4.9%, P < 0.01). Importantly, the proximal tibial growth plates were closed in all old ERαAF-10mice while they were open in all WT mice. Growth plate closure was associated with a significantly altered balance between chondrocyte proliferation and apoptosis in the growth plate. In conclusion, old female ERα−/−mice display a prolonged and enhanced longitudinal bone growth associated with increased growth plate height, resembling the growth phenotype of patients with inactivating mutations in ERα or aromatase. In contrast, ERαAF-1 deletion results in a hyperactive ERα, altering the chondrocyte proliferation/apoptosis balance, leading to growth plate closure. This suggests that growth plate closure is induced by functions of ERα that do not require AF-1 and that ERαAF-1 opposes growth plate closure.
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| 9. |
- Börjesson, Anna E, et al.
(author)
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The role of estrogen receptor-alpha and its activation function-1 for growth plate closure in female mice
- 2012
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In: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 302:11, s. E1381-E1389
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Journal article (peer-reviewed)abstract
- Borjesson AE, Windahl SH, Karimian E, Eriksson EE, Lagerquist MK, Engdahl C, Antal MC, Krust A, Chambon P, Savendahl L, Ohlsson C. The role of estrogen receptor-alpha and its activation function-1 for growth plate closure in female mice. Am J Physiol Endocrinol Metab 302: E1381-E1389, 2012. First published March 13, 2012; doi:10.1152/ajpendo.00646.2011.-High estradiol levels in late puberty induce growth plate closure and thereby cessation of growth in humans. In mice, the growth plates do not fuse after sexual maturation, but old mice display reduced longitudinal bone growth and high-dose estradiol treatment induces growth plate closure. Estrogen receptor (ER)-alpha stimulates gene transcription via two activation functions (AFs), AF-1 and AF-2. To evaluate the role of ER alpha and its AF-1 for age-dependent reduction in longitudinal bone growth and growth plate closure, female mice with inactivation of ER alpha (ER alpha(-/-)) or ER alpha AF-1 (ER alpha AF-1(0)) were evaluated. Old (16- to 19-mo-old) female ER alpha(-/-) mice showed continued substantial longitudinal bone growth, resulting in longer bones (tibia: +8.3%, P < 0.01) associated with increased growth plate height (+18%, P < 0.05) compared with wild-type (WT) mice. In contrast, the longitudinal bone growth ceased in old ER alpha AF-1(0) mice (tibia: -4.9%, P < 0.01). Importantly, the proximal tibial growth plates were closed in all old ER alpha AF-1(0) mice while they were open in all WT mice. Growth plate closure was associated with a significantly altered balance between chondrocyte proliferation and apoptosis in the growth plate. In conclusion, old female ER alpha(-/-) mice display a prolonged and enhanced longitudinal bone growth associated with increased growth plate height, resembling the growth phenotype of patients with inactivating mutations in ER alpha or aromatase. In contrast, ER alpha AF-1 deletion results in a hyperactive ER alpha, altering the chondrocyte proliferation/apoptosis balance, leading to growth plate closure. This suggests that growth plate closure is induced by functions of ER alpha that do not require AF-1 and that ER alpha AF-1 opposes growth plate closure.
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| 10. |
- Ejdesjö, Andreas, et al.
(author)
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Genetic and environmental influence on diabetic rat embryopathy
- 2011
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In: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 300:3, s. E454-E467
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Journal article (peer-reviewed)abstract
- We assessed genetic and environmental influence on fetal outcome in diabetic rat pregnancy. Crossing normal (N) and manifestly diabetic (MD) Wistar Furth (W) and Sprague-Dawley (L) females with W or L males yielded 4 different fetal genotypes (WW, LL, WL, LW) in N or MD rat pregnancies for studies. We also evaluated fetal outcome in litters with enhanced or diminished severity of maternal MD state, denoted MD(+)WL and MD(-)LW. The MDWW litters had less malformations and resorptions (0% and 19%) than the MDLL litters (17% and 30%). The MDWL litters (0% and 8%) were less maldeveloped than the MDLW litters (9% and 22%), whereas the MD(+)WL (3% and 23%) and MD(-)LW (1% and 17%) litters showed increased and decreased dysmorphogenesis (compared to MDWL and MDLW litters). The pregnant MDW rats had lower serum levels of glucose, fructosamine and branched chain amino acids than the pregnant MDL rats, whereas the pregnant MD(+)W and MD(-)L rats had levels comparable to those of the MDL and MDW rats, respectively. The 8-iso-PGF2α levels of the malformed MDLW offspring were increased compared to the non-malformed MDLW offspring. Diabetes decreased fetal heart Ret and increased Bmp-4 gene expression in the MDLW offspring, and caused decreased GDNF and Shh expression in the malformed fetal mandible of the MDLW offspring. We conclude that the fetal (epi)genome controls the embryonic dysmorphogenesis in diabetic pregnancy by instigating a threshold level for the teratological insult, and that the maternal genome controls the teratogenic insult by (dys)regulating the maternal metabolism.
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