scholarly journals Metabolic and hormonal interactions between muscle and adipose tissue

2004 ◽  
Vol 63 (2) ◽  
pp. 381-385 ◽  
Author(s):  
Eva Tomas ◽  
Meghan Kelly ◽  
Xiaoqin Xiang ◽  
Tsu-Shuen Tsao ◽  
Charlotte Keller ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Protein Kinase ◽  
Leptin Receptor ◽  
Acid Oxidation ◽  
Peripheral Tissues ◽  
Endocrine Organ ◽  
Energy Needs ◽  
Physiological Relevance ◽  
Amp Activated Protein Kinase

From the perspective of a muscle physiologist, adipose tissue has long been perceived predominantly as a fuel reservoir that provides muscle and other tissues with NEFA when exogenous nutrients are insufficient for their energy needs. Recently, studies have established that adipose tissue is also an endocrine organ. Among the hormones it releases are adiponectin and leptin, both of which can activate AMP-activated protein kinase and increase fatty acid oxidation in skeletal muscle and probably other tissues. Deficiencies of leptin or leptin receptor, adiponectin and IL-6 are associated with obesity, insulin resistance and a propensity to type 2 diabetes. In addition, a lack of adiponectin has been linked to atherosclerosis. Whether this pathology reflects a deficient activation of AMP-activated protein kinase in peripheral tissues remains to be determined. Finally, recent studies have suggested that skeletal muscle may also function as an endocrine organ when it releases the cytokine IL-6 into the circulation during sustained exercise. Interestingly, one of the apparent effects of IL-6 is to stimulate lipolysis, causing the release of NEFA from the adipocyte. Thus, hormonal communications exist between the adipocyte and muscle that could enable them to talk to each other. The physiological relevance of this cross talk clearly warrants further study.

Role of the AMP-activated protein kinase in regulating fatty acid metabolism during exerciseThis 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. 315-322 ◽  
Author(s):  
Gregory R. Steinberg
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Moderate Intensity ◽  
Amp Activated Protein Kinase

During moderate-intensity exercise, fatty acids are the predominant substrate for working skeletal muscle. The release of fatty acids from adipose tissue stores, combined with the ability of skeletal muscle to actively fine tune the gradient between fatty acid and carbohydrate metabolism, depending on substrate availability and energetic demands, requires a coordinated system of metabolic control. Over the past decade, since the discovery that AMP-activated protein kinase (AMPK) was increased in accordance with exercise intensity, there has been significant interest in the proposed role of this ancient stress-sensing kinase as a critical integrative switch controlling metabolic responses during exercise. In this review, studies examining the role of AMPK as a regulator of fatty acid metabolism in both adipose tissue and skeletal muscle during exercise will be discussed. Exercise induces activation of AMPK in adipocytes and regulates triglyceride hydrolysis and esterfication through phosphorylation of hormone sensitive lipase (HSL) and glycerol-3-phosphate acyl-transferase, respectively. In skeletal muscle, exercise-induced activation of AMPK is associated with increases in fatty acid uptake, phosphorylation of HSL, and increased fatty acid oxidation, which is thought to occur via the acetyl-CoA carboxylase-malony-CoA-CPT-1 signalling axis. Despite the importance of AMPK in regulating fatty acid metabolism under resting conditions, recent evidence from transgenic models of AMPK deficiency suggest that alternative signalling pathways may also be important for the control of fatty acid metabolism during exercise.

Effect of phosphorylation by AMP-activated protein kinase on palmitoyl-CoA inhibition of skeletal muscle acetyl-CoA carboxylase

2005 ◽  
Vol 98 (4) ◽  
pp. 1221-1227 ◽  
Author(s):  
D. S. Rubink ◽  
W. W. Winder
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Oxidation Rates ◽  
Malonyl Coa ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) has previously been demonstrated to phosphorylate and inactivate skeletal muscle acetyl-CoA carboxylase (ACC), the enzyme responsible for synthesis of malonyl-CoA, an inhibitor of carnitine palmitoyltransferase 1 and fatty acid oxidation. Contraction-induced activation of AMPK with subsequent phosphorylation/inactivation of ACC has been postulated to be responsible in part for the increase in fatty acid oxidation that occurs in muscle during exercise. These studies were designed to answer the question: Does phosphorylation of ACC by AMPK make palmitoyl-CoA a more effective inhibitor of ACC? Purified rat muscle ACC was subjected to phosphorylation by AMPK. Activity was determined on nonphosphorylated and phosphorylated ACC preparations at acetyl-CoA concentrations ranging from 2 to 500 μM and at palmitoyl-CoA concentrations ranging from 0 to 100 μM. Phosphorylation resulted in a significant decline in the substrate saturation curve at all palmitoyl-CoA concentrations. The inhibitor constant for palmitoyl-CoA inhibition of ACC was reduced from 1.7 ± 0.25 to 0.85 ± 0.13 μM as a consequence of phosphorylation. At 0.5 mM citrate, ACC activity was reduced to 13% of control values in response to the combination of phosphorylation and 10 μM palmitoyl-CoA. Skeletal muscle ACC is more potently inhibited by palmitoyl-CoA after having been phosphorylated by AMPK. This may contribute to low-muscle malonyl-CoA values and increasing fatty acid oxidation rates during long-term exercise when plasma fatty acid concentrations are elevated.

Skeletal muscle basal AMP-activated protein kinase activity is chronically elevated in alloxan-diabetic dogs: impact of exercise

2003 ◽  
Vol 95 (4) ◽  
pp. 1523-1530 ◽  
Author(s):  
Michael J. Christopher ◽  
Zhi-Ping Chen ◽  
Christian Rantzau ◽  
Bruce E. Kemp ◽  
Frank P. Alford
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Vastus Lateralis ◽  
Glucose Disposal ◽  
Protein Kinase Activity ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Peripheral Tissues ◽  
Diabetic Dogs ◽  
Amp Activated Protein Kinase

The effect of diabetes and exercise on skeletal muscle (SkM) AMP-activated protein kinase (AMPK)α1 and -α2 activities and site-specific phosphorylation of acetyl-CoA carboxylase was examined in the same six dogs before alloxan (35 mg/kg)-induced diabetes (C) and after 4-5 wk of suboptimally controlled hyperglycemic and hypoinsulinemic diabetes (DHG) in the presence and absence of 300-min phlorizin (50 μg·kg-1·min-1)-induced “normoglycemia” (DNG). In each study, the dog underwent a 150-min [3-3H]glucose infusion period, followed by a 30-min treadmill exercise test (60-70% maximal oxygen capacity) to measure the rate of glucose disposal into peripheral tissues (Rdtissue). SkM biopsies were taken from the thigh (vastus lateralis) before and immediately after exercise. In the C and DHG states, the rise in plasma free fatty acids (FFA) with exercise (∼40%) was similar. In the DNG group, preexercise FFA were significantly higher, but the absolute rise in FFA with exercise was similar. However, the exercise-induced increment in Rdtissue was significantly blunted (by ∼40-50%) in the DNG group compared with the other states. In SkM, preexercise AMPKα1 and -α2 activities were significantly elevated (by ∼60-125%) in both diabetic states, but unlike the C group these activities did not rise further with exercise. Additionally, preexercise acetyl-CoA carboxylase phosphorylation in both diabetic states was elevated by ∼70-80%, but the increases with exercise were similar to the C group. Preexercise AMPKα1 and -α2 activities were negatively correlated with Rdtissue during exercise for the combined groups (both P < 0.02). In conclusion, the elevated preexercise SkM AMPKα1 and -α2 activities contribute to the ongoing basal supply of glucose and fatty acid metabolism in suboptimally controlled hypoinsulinemic diabetic dogs; but whether they also play a permissive role in the metabolic stress response to exercise remains uncertain.

AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle

1997 ◽  
Vol 273 (6) ◽  
pp. E1107-E1112 ◽  
Author(s):  
G. F. Merrill ◽  
E. J. Kurth ◽  
D. G. Hardie ◽  
W. W. Winder
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Fatty Acid Oxidation ◽  
Fold Increase ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase ◽  
Malonyl Coa ◽  
Amp Activated Protein Kinase

5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) has previously been reported to be taken up into cells and phosphorylated to form ZMP, an analog of 5′-AMP. This study was designed to determine whether AICAR can activate AMP-activated protein kinase (AMPK) in skeletal muscle with consequent phosphorylation of acetyl-CoA carboxylase (ACC), decrease in malonyl-CoA, and increase in fatty acid oxidation. Rat hindlimbs were perfused with Krebs-Henseleit bicarbonate containing 4% bovine serum albumin, washed bovine red blood cells, 200 μU/ml insulin, and 10 mM glucose with or without AICAR (0.5–2.0 mM). Perfusion with medium containing AICAR was found to activate AMPK in skeletal muscle, inactivate ACC, and decrease malonyl-CoA. Hindlimbs perfused with 2 mM AICAR for 45 min exhibited a 2.8-fold increase in fatty acid oxidation and a significant increase in glucose uptake. No difference was observed in oxygen uptake in AICAR vs. control hindlimb. These results provide evidence that decreases in muscle content of malonyl-CoA can increase the rate of fatty acid oxidation.

Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise

1996 ◽  
Vol 270 (2) ◽  
pp. E299-E304 ◽  
Author(s):  
W. W. Winder ◽  
D. G. Hardie
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Ammonium Sulfate ◽  
Quadriceps Muscle ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase ◽  
Rat Skeletal Muscle ◽  
Malonyl Coa ◽  
Amp Activated Protein Kinase

Malonyl-CoA, an inhibitor of fatty acid oxidation in skeletal muscle mitochondria, decreases in rat skeletal muscle during exercise or in response to electrical stimulation. Regulation of rat skeletal muscle acetyl-CoA carboxylase (ACC), the enzyme that synthesizes malonyl-CoA, was studied in vitro and in vivo. Avidin-Sepharose affinity-purified ACC from hindlimb skeletal muscle was phosphorylated by purified liver AMP-activated protein kinase with a concurrent decrease in ACC activity. AMP-activated protein kinase was quantitated in resuspended ammonium sulfate precipitates of the fast-twitch red (type IIa fibers) region of the quadriceps muscle. Rats running on a treadmill at 21 m/min up a 15% grade show a 2.4-fold activation of AMP-activated protein kinase concurrently with a marked decrease in ACC activity in the resuspended ammonium sulfate precipitates at all citrate concentrations ranging from 0 to 20 mM. Malonyl-CoA decreased from a resting value of 1.85 +/- 0.29 to 0.50 +/- 0.09 nmol/g in red quadriceps muscle after 30 min of treadmill running. The activation of the AMP-activated protein kinase with consequent phosphorylation and inactivation of ACC may be one of the primary events in the control of malonyl-CoA and hence fatty acid oxidation during exercise.

Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR

2004 ◽  
Vol 287 (2) ◽  
pp. E310-E317 ◽  
Author(s):  
Kei Sakamoto ◽  
Olga Göransson ◽  
D. Grahame Hardie ◽  
Dario R. Alessi
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Muscle Contraction ◽  
Cultured Cells ◽  
Muscle Fiber Types ◽  
Fiber Types ◽  
Physiological Relevance ◽  
Lkb1 Tumor Suppressor ◽  
Sciatic Nerve Stimulation ◽  
Amp Activated Protein Kinase

Activation of AMP-activated protein kinase (AMPK) by exercise and metformin is beneficial for the treatment of type 2 diabetes. We recently found that, in cultured cells, the LKB1 tumor suppressor protein kinase activates AMPK in response to the metformin analog phenformin and the AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR). We have also reported that LKB1 activates 11 other AMPK-related kinases. The activity of LKB1 or the AMPK-related kinases has not previously been studied in a tissue with physiological relevance to diabetes. In this study, we have investigated whether contraction, phenformin, and AICAR influence LKB1 and AMPK-related kinase activity in rat skeletal muscle. Contraction in situ, induced via sciatic nerve stimulation, significantly increased AMPKα2 activity and phosphorylation in multiple muscle fiber types without affecting LKB1 activity. Treatment of isolated skeletal muscle with phenformin or AICAR stimulated the phosphorylation and activation of AMPKα1 and AMPKα2 without altering LKB1 activity. Contraction, phenformin, or AICAR did not significantly increase activities or expression of the AMPK-related kinases QSK, QIK, MARK2/3, and MARK4 in skeletal muscle. The results of this study suggest that muscle contraction, phenformin, or AICAR activates AMPK by a mechanism that does not involve direct activation of LKB1. They also suggest that the effects of excercise, phenformin, and AICAR on metabolic processes in muscle may be mediated through activation of AMPK rather than activation of LKB1 or the AMPK-related kinases.

IL-6 selectively stimulates fat metabolism in human skeletal muscle

2010 ◽  
Vol 299 (5) ◽  
pp. E832-E840 ◽  
Author(s):  
Emil Wolsk ◽  
Helene Mygind ◽  
Thomas S. Grøndahl ◽  
Bente K. Pedersen ◽  
Gerrit van Hall
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Glucose Metabolism ◽  
Acid Oxidation ◽  
Fourfold Increase ◽  
Metabolic Role ◽  
Acute Increase ◽  
Amp Activated Protein Kinase

Interleukin (IL)-6 is chronically elevated in type 2 diabetes but also during exercise. However, the exact metabolic role, and hence the physiological significance, has not been elucidated. The objective of this study was to investigate the in vivo effect of recombinant human (rh) IL-6 on human fat and glucose metabolism and signaling of both adipose tissue and skeletal muscle. Eight healthy postabsorptive males were infused with either rhIL-6 or saline for 4 h, eliciting IL-6 levels of ∼40 and ∼1 pg/ml, respectively. Systemic, skeletal muscle, and adipose tissue fat and glucose metabolism was assessed before, during, and 2 h after cessation of the infusion. Glucose metabolism was unaffected by rhIL-6. In contrast, rhIL-6 increased systemic fatty acid oxidation approximately twofold after 60 min, and it remained elevated even 2 h after the infusion. The increase in oxidation was followed by an increase in systemic lipolysis. Adipose tissue lipolysis and fatty acid kinetics were unchanged with rhIL-6 compared with saline infusion. Conversely, rhIL-6 infusion caused an increase in skeletal muscle unidirectional fatty acid and glycerol release, indicative of an increase in lipolysis. The increased lipolysis in muscle could account for the systemic changes. Skeletal muscle signaling increased after 1 h of rhIL-6 infusion, indicated by a fourfold increase in the phosphorylated signal transducer and activator of transcription (STAT) 3-to-STAT3 ratio, whereas no changes in phosphorylated AMP-activated protein kinase or acetyl-CoA carboxylase levels could be observed. Our findings suggest that an acute increase in IL-6 at a normophysiological level selectively stimulates lipolysis in skeletal muscle, whereas adipose tissue is unaffected.

Prolonged exposure to palmitate impairs fatty acid oxidation despite activation of AMP-activated protein kinase in skeletal muscle cells

2008 ◽  
Vol 217 (2) ◽  
pp. 478-485 ◽  
Author(s):  
A.S. Pimenta ◽  
M.P. Gaidhu ◽  
S. Habib ◽  
M. So ◽  
S. Fediuc ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Oxidation ◽  
Prolonged Exposure ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Acid Oxidation ◽  
Amp Activated Protein Kinase

scholarly journals Skeletal muscle AMP-activated protein kinase γ1H151R overexpression enhances whole body energy homeostasis and insulin sensitivity

2015 ◽  
Vol 309 (7) ◽  
pp. E679-E690 ◽  
Author(s):  
Milena Schönke ◽  
Martin G. Myers ◽  
Juleen R. Zierath ◽  
Marie Björnholm
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Protein Kinase ◽  
Transgenic Mice ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Α Subunit ◽  
Peripheral Tissues ◽  
Amp Activated Protein Kinase ◽  
Body Energy

AMP-activated protein kinase (AMPK) is a major sensor of energy homeostasis and stimulates ATP-generating processes such as lipid oxidation and glycolysis in peripheral tissues. The heterotrimeric enzyme consists of a catalytic α-subunit, a β-subunit that is important for enzyme activity, and a noncatalytic γ-subunit that binds AMP and activates the AMPK complex. We generated a skeletal muscle Cre-inducible transgenic mouse model expressing a mutant γ1-subunit (AMPKγ1H151R), resulting in chronic AMPK activation. The expression of the predominant AMPKγ3 isoform in skeletal muscle was reduced in extensor digitorum longus (EDL) muscle (81–83%) of AMPKγ1H151R transgenic mice, whereas the abundance and phosphorylation of the AMPK target acetyl-CoA carboxylase was increased in tibialis anterior muscle. Glycogen content was increased 10-fold in gastrocnemius muscle. Whole body carbohydrate oxidation was increased by 11%, and whereas glucose tolerance was unaffected, insulin sensitivity was increased in AMPKγ1H151R transgenic mice. Furthermore, perigonadal white adipose tissue mass and serum leptin were reduced in female AMPKγ1H151R transgenic mice by 38 and 51% respectively. Conversely, in male AMPKγ1H151R transgenic mice, food intake was increased (14%), but body weight and body composition were unaltered, presumably because of increased energy expenditure. In conclusion, transgenic activation of skeletal muscle AMPKγ1 in this model plays an important sex-specific role in skeletal muscle metabolism and whole body energy homeostasis.

Sign in / Sign up

Export Citation Format

Share Document