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1.
Subcutaneous abdominal adipose tissue lipolysis during exercise determined by arteriovenous measurements in older women 总被引:2,自引:0,他引:2
Lange KH Lorentsen J Isaksson F Simonsen L Juul A Christensen NJ Kjaer M Bülow J 《Journal of the American Geriatrics Society》2002,50(2):275-281
OBJECTIVES: To characterize the lipolytic response in the subcutaneous abdominal adipose tissue in older women to endurance exercise. DESIGN: Cross-sectional exercise study.SETTING: Exercise laboratory, Copenhagen, Denmark. PARTICIPANTS: Seven healthy, older women (mean age +/- standard error = 75 +/- 2 years); weight: 67.8 +/- 4.9 kg; body fat: 40 +/- 3; maximal oxygen uptake (VO2max): 1.43 +/- 0.07 L.min 1). MEASUREMENTS: Body composition (dual energy x-ray absorptiometry (DEXA)), maximal oxygen uptake (VO2max, maximal cycling test), lipolytic response to exercise (arterial and adipose tissue venous catheterization at rest and during 60 minutes of continuous cycling at a load corresponding to 60 of VO2max), adipose tissue blood flow (ATBF) (133Xenon (133Xe) washout), oxygen consumption and respiratory exchange ratio during exercise (indirect calorimetry), whole blood glycerol, plasma nonesterified fatty acids (NEFA), lactate, glucose, epinephrine, norepinephrine, insulin, serum growth hormone, and hematocrit. RESULTS: Glycerol and NEFA mobilization rates increased by 250 and 180, respectively, from rest to exercise. This was achieved primarily by an increase in veno-arterial differences, because ATBF did not increase significantly. NEFA:glycerol mobilization ratio was about two at rest and remained at that level during exercise, indicating significant local reesterification in both conditions. After an initial decrease, arterial plasma NEFA concentration increased significantly, by 26, indicating that NEFA delivery exceeded muscle uptake. CONCLUSIONS: Older women are capable of prompt and substantial increase in subcutaneous abdominal adipose tissue glycerol and NEFA mobilization rates in response to moderate acute endurance exercise. The lipolytic response matches skeletal muscle NEFA uptake, and decreased ability to mobilize fat during exercise is therefore not likely to cause increased fat mass with advancing age. 相似文献
2.
E. Rudolf Froesch 《Diabetologia》1967,3(6):475-487
Summary The regulation of adipose tissue lipolysis occupies a key position in the metabolic concert of carbohydrates and lipids, and insulin plays the role of the conductor. Insulin favours the storage of fat in adipose tissue by 3 mechanisms: — 1. it inhibits lipolysis; — 2. increases the glucose uptake, lipogenesis and reësterification of free fatty acids; — 3. enhances the activity of lipoprotein-lipase, which is responsible for the uptake and storage of blood lipoproteins in adipose tissue. — On the other hand, basal lipolytic activity of adipose tissue is very much elevated in rats which are refed after prolonged starvation. It appears that insulin induces a lipase, which, in its presence, is nonfunctional. This dual role of insulin — induction of a lipase activity which it inhibits — would provide animals with a very efficient mechanism of switching from glucose utilization and lipid storage to lipid mobilization and oxidation. — High plasma levels of free fatty acids decrease glucose utilization of muscle and the effects of insulin thereon. Therefore, pharmacologic inhibition of lipolysis has been investigated in order to find new and better ways to adjust the metabolic situation in diabetes mellitus. We have used 5-methylpyrazole-3-carboxylic acid as a model antilipolytic compound. This drug, nicotinic acid and prostaglandin E1 not only inhibit lipolysis, but they also markedly enhance glucose uptake of adipose tissuein vivo. 5-methylpyrazole-3-carboxylic acid prevents the rise of the free fatty acids and of blood glucose acutely after the administration of anti-insulin serum. When this drug is administered over a period of several days, adipose tissue develops an escape mechanism; 5-methylpyrazole-3-carboxylic acid still effectively inhibits lipolysis and stimulates lipogenesis from glucose, but only for a short period of time. Basal lipolysis is activated and the newly synthesized glycerides are rapidly split and released as free fatty acids into the blood, so that soon after its administration the plasma level of free fatty acids is increased above normal. These findings shed doubt on the potential usefulness of antilipolytic drugs in the treatment of diabetes mellitus. — Purified nonsuppressible ILA of serum is mentioned as an antidiabetic substance of potential therapeutic interest since it increases glucose uptake of muscle more markedly than that of adipose tissue compared with insulin.The studies reported here were supported by the US Public Health Service (grant No. A 5387) and by the Schweizerische Nationalfonds (grant No. 3854). 相似文献
3.
AIMS: Subcutaneous microdialysis has been used for continuous glucose monitoring in patients with diabetes mellitus (DM) to facilitate tight regulation of blood glucose levels. The aims of this study were therefore to investigate (i) the relationship between capillary and interstitial glucose in patients with type 1 or 2 DM and healthy subjects and (ii) the feasibility of using microdialysis to assess local insulin sensitivity in adipose tissue. METHODS: Using subcutaneous microdialysis, interstitial glucose, lactate, pyruvate and glycerol were determined as measures of glucose and lipid metabolism in adipose tissue, before and after an oral glucose tolerance test (OGTT) in 14 patients and seven controls. The results were correlated to whole-body insulin sensitivity and insulin sensitivity in liver estimated from the levels of insulin-like growth factor-binding protein 1 (IGFBP-1). RESULTS: Capillary and interstitial glucose correlated before and after OGTT in healthy subjects and in type 1 DM but not in type 2 DM. In fasting state, the glycerol levels were higher in both type 1 and type 2 DM compared with controls. After the OGTT, the insulin levels were sufficient to suppress lipolysis in type 1 but not in type 2 DM. The glucose/lactate ratio was higher at fasting in type 1 DM and after OGTT in type 1 and 2 DM. In type 1 DM, basal interstitial glycerol levels correlated to whole-body glucose utilization. In type 2 DM, correlations were found between the basal glycerol levels and whole-body insulin sensitivity and between glucose/lactate and per cent decrease in IGFBP-1 levels 120 min after OGTT. CONCLUSION: Capillary and interstitial glucose correlated before and after OGTT in healthy subjects and patients with type 1 DM. Correlations were also found between insulin sensitivity in whole body and in adipose tissue in both type 1 and type 2 DM and between insulin sensitivity in subcutaneous adipose tissue and liver in type 2 DM. This study shows that microdialysis technique can be used to study in vivo insulin sensitivity in adipose tissue over time and may be useful in the evaluation of, for example, the effects of new drugs on insulin sensitivity. 相似文献
4.
Hayley M. O’Neill Graham P. Holloway Gregory R. Steinberg 《Molecular and cellular endocrinology》2013
Skeletal muscle plays an important role in regulating whole-body energy expenditure given it is a major site for glucose and lipid oxidation. Obesity and type 2 diabetes are causally linked through their association with skeletal muscle insulin resistance, while conversely exercise is known to improve whole body glucose homeostasis simultaneously with muscle insulin sensitivity. Exercise activates skeletal muscle AMP-activated protein kinase (AMPK). AMPK plays a role in regulating exercise capacity, skeletal muscle mitochondrial content and contraction-stimulated glucose uptake. Skeletal muscle AMPK is also thought to be important for regulating fatty acid metabolism; however, direct genetic evidence in this area is currently lacking. This review will discuss the current paradigms regarding the influence of AMPK in regulating skeletal muscle fatty acid metabolism and mitochondrial biogenesis at rest and during exercise, and highlight the potential implications in the development of insulin resistance. 相似文献
5.
Recombinant human FIZZ3/resistin stimulates lipolysis in cultured human adipocytes, mouse adipose explants, and normal mice 总被引:6,自引:0,他引:6
Ort T Arjona AA MacDougall JR Nelson PJ Rothenberg ME Wu F Eisen A Halvorsen YD 《Endocrinology》2005,146(5):2200-2209
Human FIZZ3 (hFIZZ3) was identified as an ortholog of mouse resistin (mResistin), an adipocyte-specific secreted factor linked to insulin resistance in rodents. Unlike mResistin, hFIZZ3 is expressed in macrophages and monocytes, but is undetectable in adipose tissue. The profound macrophage infiltration of adipose that occurs during obesity suggests that hFIZZ3 may play an important role in adipocyte biology. Using a recombinant protein produced in Escherichia coli, we report here that chronic treatment of cultured human adipocytes with hFIZZ3 results in hypotropic cells with smaller lipid droplets. Recombinant hFIZZ3 facilitates preadipocyte proliferation and stimulates adipocyte triglyceride lipolysis, whereas recombinant mResistin inhibits adipocyte differentiation, with no detectable effect on proliferation or lipolysis. In addition, insulin-stimulated glucose uptake and Akt phosphorylation are not altered in hFIZZ3-treated adipocytes, indicating an intact insulin response. In mouse adipose explants, hFIZZ3 accelerates simultaneously triglyceride lipolysis and fatty acid reesterification, as assessed by measurement of glycerol and fatty acid release. Consistent with the in vitro findings, acute administration of recombinant hFIZZ3 into normal mice caused a significant increase in serum glycerol concentration with no elevation in free fatty acid at 45 min post injection. Taken together, the data suggest that recombinant hFIZZ3 can influence adipose metabolism by regulating preadipocyte cell number, adipocyte lipid content, and energy expenditure via accelerating the fatty acid/triglyceride futile cycle. 相似文献
6.
M Flechtner-Mors H H Ditschuneit C P Jenkinson A Alt G Adler 《Diabetic medicine》1999,16(12):1000-1006
AIMS: Metformin has been reported to decrease the plasma concentrations of non-esterified fatty acids in Type 2 diabetic subjects. This study investigated the effects of metformin on basal and catecholamine-stimulated lipolysis in abdominal subcutaneous adipose tissue of obese, hyperinsulinaemic, hypertensive subjects. METHODS: Fourteen subjects with severe obesity (12 female, twomale, age 35.4 +/- 4 years, body mass index 48.2 +/- 2 kg/m2, body fat mass 63.3 +/- 5 kg) were recruited. Glycerol and lactate concentrations were determined in the presence of metformin and after administration of catecholamines using microdialysis. Simultaneously, blood flow was assessed with the ethanol escape method. RESULTS: Glycerol release was lowered by metformin during the 3-h experiment (P<0.01). The lipolytic activity of catecholamines was suppressed when adipose tissue was pre-treated with metformin (P<0.001). Lactate concentration increased after application of metformin (P<0.01) and catecholamines (P<0.001). Blood flow was decreased in the presence of adrenaline (P < 0.01), but this effect was abolished by metformin. CONCLUSIONS: The present data demonstrate the effects of metformin on lipolysis in subcutaneous adipose tissue in vivo. In the large body fat mass of obese subjects, a reduction of lipolysis in adipose tissue may contribute to a decrease of VLDL synthesis in the liver resulting in a lowered plasma triglyceride concentration. 相似文献
7.
Summary It is not clear how circadian lipolysis and circulating concentrations of non-esterified fatty acids (NEFA) are altered in
intensively treated insulin-dependent diabetic (IDDM) patients. Ten IDDM patients on an intensive insulin regimen and eight
healthy control subjects were investigated under ordinary living conditions for 27 h by microdialysis of subcutaneous adipose
tissue. The true tissue glycerol concentration and adipose blood flow changes were monitored as an index of lipolysis. A circadian
pattern in adipose tissue lipolysis was observed in both groups, decreasing during the day and increasing during evening-night.
The daytime decrease was normal, but the evening-night rise was elevated in IDDM (p = 0.03). Circulating NEFA decreased during the day and increased at night. The latter increase was enhanced threefold in
IDDM (p = 0.003) and correlated with fasting glucose levels (r = 0.77). Nocturnal growth hormone (GH) was increased fivefold in IDDM and correlated to nocturnal lipolysis (r = 0.83). Adipose tissue blood flow increased during the night in a similar fashion in both groups. Near-normalization of
glucose for 24 h in IDDM did not affect the nocturnal increases in NEFA, GH and lipolysis. In conclusion, a circadian rhythm
in lipolysis was found. Increased lipolytic rates during evening-night may at least in part raise nocturnal circulating NEFA.
Nocturnal NEFA and lipolysis are further enhanced in IDDM, maybe due to elevated GH, but not to insulinopenia or hyperglycaemia.
[Diabetologia (1997) 40: 1070–1078]
Received: 27 February 1997 and in revised form: 28 April 1997 相似文献
8.
Changes in extracellular osmolality, and thus in the cellular hydration state, appear to directly influence cell metabolism. The metabolic changes associated with cell swelling are inhibition of glycogenolysis, glycolysis, and proteolysis. Recent studies in our laboratory demonstrated diminished whole-body protein breakdown in humans during an acute hypoosmolar state. Because of the close interrelationship between carbohydrate and fat metabolism, we speculated that adipose tissue lipolysis and fatty acid oxidation are regulated by changes in extracellular osmolality. Therefore, we investigated the effect of artificially induced hypoosmolality on whole-body lipolysis and fat oxidation in seven healthy young men. Hypoosmolality was induced by intravenous administration of desmopressin, liberal ingestion of water, and infusion of hypotonic (0.45%) saline solution. Lipolysis was assessed by a stable-isotope method (2-[13C]-glycerol infusion). The glycerol rate of appearance (Ra), reflecting whole-body lipolysis, was higher under hypoosmolar compared with isoosmolar conditions (2.35+/-0.40 v 1.68+/-0.21 micromol/kg/min, P=.03). This was even more pronounced when lipolysis was suppressed during hyperinsulinemia and euglycemic clamping (0.90+/-0.08 v 0.61+/-0.03 micromol/kg/min, P=.002). However, plasma free fatty acid (FFA), glycerol, ketone body, insulin, and glucagon concentrations and carbohydrate and lipid oxidation measured by indirect calorimetry were not significantly altered by hypoosmolality. Plasma norepinephrine concentrations were lower under hypoosmolar conditions (P<.01 v control). In conclusion, hypoosmolality in vivo results in increased whole-body lipolysis, which is not due to changes in major lipolysis regulating hormones. 相似文献
9.
Burns N Finucane FM Hatunic M Gilman M Murphy M Gasparro D Mari A Gastaldelli A Nolan JJ 《Diabetologia》2007,50(7):1500-1508
Aims/hypothesis Early-onset type 2 diabetes is associated with marked visceral obesity and extreme insulin resistance, but its pathogenesis
and response to treatment are not completely understood. We studied physical fitness, whole-body and hepatic glucose turnover,
and insulin secretion in young obese Irish subjects before and after 3 months of aerobic exercise training. We hypothesised
that exercise alone, with stable diet, should improve insulin sensitivity.
Materials and methods Anthropometric parameters and maximum volume of oxygen utilisation (VO2max) were measured in 13 subjects with type 2 diabetes and 18 non-diabetic control subjects, matched for age and BMI. Insulin
sensitivity and hepatic glucose turnover were measured using the hyperinsulinaemic–euglycaemic clamp. Insulin secretion was
assessed from an OGTT and a modified intravenous glucose tolerance test. Some subjects (seven type 2 diabetic, 14 non-diabetic
control subjects) then completed a 12-week supervised aerobic exercise programme. All measurements were repeated on completion
of the exercise programme.
Results Type 2 diabetic subjects had higher WHR, systolic blood pressure and triacylglycerols than non-diabetic control subjects.
They were significantly more insulin-resistant as measured both by the clamp and oral glucose insulin sensitivity. They also
displayed marked defects in insulin secretion in response to oral and intravenous glucose challenges. Exercise intervention
had no significant effect on whole-body or hepatic insulin sensitivity or insulin secretion. VO2max increased significantly in the non-diabetic control subjects, but not in the type 2 diabetic subjects after exercise training.
Conclusions/interpretation Young obese subjects with type 2 diabetes are severely insulin-resistant with marked loss of beta cell function compared with
control subjects matched for age and obesity. Neither group responded metabolically to aerobic exercise intervention.
N. Burns and F. M. Finucane contributed equally to this work. 相似文献
10.
Nielsen S Levine J Clay R Jensen MD 《The Journal of clinical endocrinology and metabolism》2001,86(6):2717-2720
Type 2 benign symmetric lipomatosis (BSL) is characterized by abnormal growth of adipose tissue in the upper back, deltoid region, upper arms, hips, and upper thigh region. Studies of lipomatous tissue in vitro have suggested that defective lipolysis may account for excess fat accumulation; however, in vivo adipose tissue metabolism has not been evaluated. We measured systemic adipose tissue lipolysis and regional adipose tissue fatty acid uptake in a patient with type 2 BSL scheduled for elective brachioplasty. We found increased, rather than decreased, rates of systemic free fatty acid release coupled with normal fatty acid oxidation. The uptake of fatty acids was 19% greater in deltoid region lipomatous tissue than in abdominal sc fat, whereas in control studies the relative uptake of fatty acids in deltoid fat averaged 29% less than that in abdominal fat. Adipocyte size was smaller than expected in lipomatous tissue. These results suggest that type 2 BSL is a hyperplastic adipose tissue abnormality that does not impair systemic lipolysis. The pathophysiology appears similar to what has been termed hyperplastic obesity. A better understanding of this condition could lead to insights into the mechanisms of hyperplastic obesity. 相似文献
11.
M Cahova H Vavrinkova E Meschisvilli I Markova L Kazdova 《Experimental and clinical endocrinology & diabetes》2004,112(10):549-555
The aim of the study was to determine the contribution of skeletal muscle, adipose tissue and liver to the impaired glucose clearance manifesting itself during the initial phase of OGTT in a non-obese animal model of insulin resistance, hereditary hypertriglyceridemic (HHTg) rats. Glucose utilisation and storage in insulin target tissues in vivo and in vitro after a glucose load (3 g/kg b. wt.) administered intragastrically following overnight fasting was compared in adult male HHTg rats and Wistar normotriglyceridemic controls after short-term (2 wk) high-sucrose (70 % calories as sucrose) feeding period. In comparison with normotriglyceridemic controls, in HHTg rats the glucose administration did not stimulate GLUT4 translocation to the plasma membrane in skeletal muscle and adipose tissue that was associated with decreased glucose utilisation by these tissues in vitro. The acute glucose supply did not result in increased glycogen synthesis in the liver and fatty acid synthesis de novo in adipose tissue. On the contrary, the serum glucose, triglyceride and free fatty acid levels remained elevated. In conclusion, in the tissues of HHTg rats, despite the increased insulinemia, the processes leading toward increased glucose utilisation and processes transforming glucose into storage forms, such as triglycerides in adipose tissue and glycogen in skeletal muscle and liver, did not start within this time interval. The combination of the impaired glucose utilisation and the impaired glucose storage in energy reserves leads to higher glycaemia following glucose load in HHTg rats. 相似文献
12.
Increased lipolysis in adipose tissue and lipid mobilization to natriuretic peptides during low-calorie diet in obese women. 总被引:2,自引:0,他引:2
C Sengenes V Stich M Berlan J Hejnova M Lafontan Z Pariskova J Galitzky 《International journal of obesity (2005)》2002,26(1):24-32
OBJECTIVE: We recently demonstrated that natriuretic peptides (NP) are involved in a pathway inducing lipolysis in human adipose tissue. Atrial NP (ANP) and brain NP (BNP) operate via a cGMP-dependent pathway which does not involve phosphodiesterase-3B inhibition or cAMP. The study was performed to evaluate the effect of ANP on lipid mobilization in obese women and secondly to examine the possible effect of a low-calorie diet (LCD) on the lipolytic response of subcutaneous abdominal fat cells to NP and on the lipid mobilization induced by ANP infusion (1 microg/m(2) min for 60 min). SUBJECTS: Ten obese women from 40.5+/-3.4 y old were selected for this study. Their body weight was 96.4+/-5.7 kg and their BMI was 35.3+/-1.7 kg/m(2). They received a 2.5-2.9 MJ/day formula diet for 28 days. DESIGN: Before and during the LCD, an adipose tissue biospy was performed for in vitro studies and, moreover, ANP was perfused i.v. to evaluate its lipid mobilizing action in toto and in situ in subcutaneous abdominal adipose tissue (SCAAT) using microdialysis. RESULTS: The lipolytic effects of isoproterenol, ANP, BNP and bromo-cGMP (an analogue of cGMP) on fat cells increased by about 80-100% during LCD. The lipid mobilization during i.v. ANP infusion, assessed by plasma non-esterified fatty acids (NEFA) increase was enhanced during the LCD. However, during LCD, ANP infusion induced a biphasic effect on glycerol concentration in plasma and interstitial fluid of SCAAT; a significant increase was observed in glycerol levels during the first 30 min infusion period, followed by a steady decrease. The concentration of glycerol was lower during the post-infusion period than during the baseline period. This effect was stronger in obese subjects submitted to the LCD with a low-carbohydrate composition. Other plasma parameters were weakly increased (noradrenaline) or not modified (insulin, glucose) by ANP infusion and no difference was found before and during LCD treatment. CONCLUSION: The present study shows that NP are powerful lipolytic agents in subcutaneous fat cells and that both isoproterenol- and NP-induced lipolysis increase during LCD, in obese women. These changes seem to be associated with an improvement of the lipolytic pathway at a post-receptor level. Moreover, i.v. administration of ANP induced a lipid mobilizing effect which was enhanced by a LCD in these objects. 相似文献
13.
Adipose tissue lipolysis and fatty acid re-esterification were examined simultaneously in vivo and in vitro in fasted human subjects receiving a constant intravenous infusion of 14C palmitate and large intravenous infusions of glucose and insulin. Under these circumstances, the plasma [FFA] declines rapidly while the specific activity of plasma FFA increases. Plasma [glycerol] remains stable or declines slowly. These in vivo changes in FFA and glycerol metabolism appear to reflect increased adipose tissue re-esterification of FFA, without an attendant decline in rate of lipolysis. However, in vitro rates of re-esterification in gluteal adipose tissue did not change sufficiently to account for the in vivo phenomena. We conclude that: (1) re-esterification in adipose tissue is an important mechanism for the decline in [FFA] induced by glucose infusion in fasted man, but in vitro studies of adipose tissue from a gluteal site do not explain the changes in plasma free fatty acid levels; (2) our data suggest that control of the net mixture of metabolic fuels leaving the adipocyte may be under the influence of pericellular blood flow in addition to ambient humoral factors or intrinsic characteristics of the adipocyte. 相似文献
14.
In a prospective, controlled study, the influence of strenuous physical exercise on plasma total cholesterol, HDL cholesterol, apolipoprotein A-I, total triglycerides and fatty acid composition of adipose tissue was studied during 7 months of training in 15 senior oarsmen and 21 controls matched for age, smoking and drinking habits. Dietary intake was monitored. At the start of the study there were no differences in lipid parameters and adipose tissue composition between oarsmen and controls. A significant decrease in total cholesterol and total triglycerides and an increase in HDL cholesterol and apolipoprotein A-I was noted in the oarsmen after only 2 weeks of training. Body weight remained stable but skin-fold thickness decreased. Food consumption increased considerably but diet composition remained unchanged. Nevertheless the fatty acid pattern of adipose tissue changed significantly, as a result of altered preferential endogenous fatty acid synthesis and/or fatty acid oxidation. Since lipid parameters and adipose tissue composition were equal in oarsmen and controls before the start of the training, it is concluded that the changes induced by exercise only last for the duration of the training period. 相似文献
15.
Summary The study was performed to investigate the effects of mild to moderate exercise on blood glucose levels, metabolite concentrations and responses of counterregulatory hormones in tightly controlled Type 1 (insulin-dependent) diabetic patients treated by continuous subcutaneous insulin infusion, and to quantify the measures necessary to prevent acute and late exercise-induced hypoglycaemia. Seven male patients started a 60 min exercise period 90 min after an insulin bolus and a standard breakfast; they were monitored during a post-exercise resting period of 5 h 30 min. Different basal and premeal insulin infusion rates were applied. (Near)normoglycaemia prevailed throughout the study during the control protocol when the subjects did not exercise and received their usual insulin dose. When they exercised without changing the insulin dose, four patients were forced to stop due to hypoglycaemia. This effect of exercise could be attenuated but not completely avoided if the basal infusion rate of insulin was discontinued during the exercise period. The pronounced increase in catecholamine and growth hormone concentrations during exercise were not sufficient to prevent hypoglycaemic reactions. Hypoglycaemia during exercise could only be prevented when the premeal insulin bolus was reduced by 50% in addition to the discontinuation of the basal insulin infusion during exercise. In order to reduce late hypoglycaemic reactions after exercise the best measure proved to be a reduction of the basal insulin infusion rate by 25% during post-exercise hours. Administration of only 50% of the basal insulin infusion rate during this time was associated with blood glucose levels being raised up to 8 mmol/l. In conclusion, Type 1 diabetic patients treated with continuous subcutaneous insulin infusion at (near)normoglycaemia need to reduce their insulin dosage before, during, and after mild to moderate endurance exercise in order to minimize the risk of acute and late hypoglycaemia. 相似文献
16.
The effects of exercise and adipose tissue lipolysis on plasma adiponectin concentration and adiponectin receptor expression in human skeletal muscle 总被引:11,自引:0,他引:11
Punyadeera C Zorenc AH Koopman R McAinch AJ Smit E Manders R Keizer HA Cameron-Smith D van Loon LJ 《European journal of endocrinology / European Federation of Endocrine Societies》2005,152(3):427-436
OBJECTIVE: It has been suggested that adiponectin regulates plasma free fatty acid (FFA) clearance by stimulating FFA uptake and/or oxidation in muscle. We aimed to determine changes in plasma adiponectin concentration and adiponectin receptor 1 and 2 mRNA expression in skeletal muscle during and after prolonged exercise under normal, fasting conditions (high FFA trial; HFA) and following pharmacological inhibition of adipose tissue lipolysis (low FFA trial; LFA). Furthermore, we aimed to detect and locate adiponectin in skeletal muscle tissue. METHODS: Ten subjects performed two exercise trials (120 min at 50% VO(2max)). Indirect calorimetry was used to determine total fat oxidation rate. Plasma samples were collected at rest, during exercise and during post-exercise recovery to determine adiponectin, FFA and glycerol concentrations. Muscle biopsies were taken to determine adiponectin protein and adiponectin receptor 1 and 2 mRNA expression and to localise intramyocellular adiponectin. RESULTS: Basal plasma adiponectin concentrations averaged 6.57+/-0.7 and 6.63+/-0.8 mg/l in the HFA and LFA trials respectively, and did not change significantly during or after exercise. In the LFA trial, plasma FFA concentrations and total fat oxidation rates were substantially reduced. However, plasma adiponectin and muscle adiponectin receptor 1 and 2 mRNA expression did not differ between trials. Immunohistochemical staining of muscle cross-sections showed the presence of adiponectin in the sarcolemma of individual muscle fibres and within the interfibrillar arterioles. CONCLUSION: Plasma adiponectin concentrations and adiponectin receptor 1 and 2 mRNA expression in muscle are not acutely regulated by changes in adipose tissue lipolysis and/or plasma FFA concentrations. Adiponectin is abundantly expressed in muscle, and, for the first time, it has been shown to be present in/on the sarcolemma of individual muscle fibres. 相似文献
17.
Increases in glucose or fatty acids affect metabolism via changes in long-chain acyl-CoA formation and chronically elevated fatty acids increase total cellular CoA. Understanding the response of pancreatic beta cells to increased amounts of fuel and the role that altered insulin secretion plays in the development and maintenance of obesity and Type 2 diabetes is important. Data indicate that the activated form of fatty acids acts as an effector molecule in stimulus-secretion coupling. Glucose increases cytosolic long-chain acyl-CoA because it increases the "switch" compound malonyl-CoA that blocks mitochondrial -oxidation, thus implementing a shift from fatty acid to glucose oxidation. We present arguments in support of the following: (i) A source of fatty acid either exogenous or endogenous (derived by lipolysis of triglyceride) is necessary to support normal insulin secretion; (ii) a rapid increase of fatty acids potentiates glucose-stimulated secretion by increasing fatty acyl-CoA or complex lipid concentrations that act distally by modulating key enzymes such as protein kinase C or the exocytotic machinery; (iii) a chronic increase of fatty acids enhances basal secretion by the same mechanism, but promotes obesity and a diminished response to stimulatory glucose; (iv) agents which raise cAMP act as incretins, at least in part, by stimulating lipolysis via beta-cell hormone-sensitive lipase activation. Furthermore, increased triglyceride stores can give higher rates of lipolysis and thus influence both basal and stimulated insulin secretion. These points highlight the important roles of NEFA, LC-CoA, and their esterified derivatives in affecting insulin secretion in both normal and pathological states.Abbreviations ACS acyl-CoA synthetase - ACC acetyl-CoA carboxylase - BAT brown adipose tissue - CPT carnitine palmitoyl transferase - CL citrate lyase - DAG diacylglycerol - GSIS glucose-stimulated insulin secretion - HSL hormone-sensitive lipase - KATP ATP-sensitive K+ channel - LC-CoA long chain acyl-CoA - PA phosphatidate - PFK-1 phosphofructokinase-1 - PKC protein kinase C - PMA phorbol myristate acetate - PC pyruvate carboxylase - PS phosphatidylserine - SNAP soluble NSF-associated protein - SNAP-25 synaptosomal-associated protein of 25 kD - t-SNARE target SNAP receptor - v-SNARE vesicle SNAP receptor - VAMP vesicle-associated membrane protein - VDCC voltage-dependent Ca2+ channel - WAT white adipose tissue 相似文献
18.
Arner P 《Best Practice & Research: Clinical Endocrinology & Metabolism》2005,19(4):471-482
Release of fatty acids (FAs) from adipose tissue through lipolysis in fat cells is a key event in many processes. FAs are not only energy substrates but also signalling molecules and substrates for lipoprotein production by the liver. Fat cells consist of>95% triglycerides that are hydrolysed during lipolysis to glycerol and FAs. The major rate-limiting factor for lipolysis is hormone-sensitive lipase, but additional lipases such as adipose tissue triglyceride lipase may also play a role. The regulation of human fat cell lipolysis is, in many ways, species unique. Only catecholamines, insulin and natriuretic peptides have pronounced acute effects. Catecholamines influence lipolysis through four different adrenoceptor subtypes, in contrast to rodents where only one subtype (beta(3)) is of major importance. There are regional variations in adipocyte lipolysis leading to more release of FAs from the visceral than subcutaneous adipose tissue during hormone stimulation (insulin, catecholamines). Since, only visceral fat is linked to the liver (by the portal vein), alterations in visceral adipocyte tissue lipolysis have direct effects on the liver through portal FA release. The regional variations in lipolysis are further enhanced in obesity and polycystic ovarian syndrome, and are of importance for dyslipidaemia, hyperinsulinaemia and glucose intolerance in these conditions. There is a marked elevation of circulating FA levels among the obese, which may be due to enhanced production of tumour necrosis factor alpha in adipose tissue. This cytokine stimulates lipolysis through so-called MAP kinases. Pharmacological agents in clinical practice such as nicotinic acid and glitazones exert lipid-lowering and glucose-lowering effects, respectively, by decreasing FA output from the adipose tissue. This review covers the biochemistry, regulation and clinical aspects of human fat cell lipolysis. 相似文献
19.
Glucocorticoids (GCs) have long been accepted as being catabolic in nature, liberating energy substrates during times of stress to supply the increased metabolic demand of the body. The effects of GCs on adipose tissue metabolism are conflicting, however, because patients with elevated GCs present with central adiposity. We performed an extensive literature review of the effects of GCs on adipose tissue metabolism. The contradictory effects of GCs on lipid metabolism occur through a number of different mechanisms, some of which are well defined and others remain to be elucidated. Firstly, through increases in caloric and dietary fat intake, along with increased hydrolysis of circulating triglycerides (chylomicrons, very low-density lipoproteins) by lipoprotein lipase activity, GCs increase the amount of fatty acids in circulation, which are then available for ectopic fat distribution (liver, muscle, and central adipocytes). Glucocorticoids also increase de novo lipid production in hepatocytes through increased expression of fatty acid synthase. There is some controversy as to whether these same mechanisms occur in adipocytes, thereby contributing to adipose hypertrophy. Glucocorticoids promote preadipocyte conversion to mature adipocytes, causing hyperplasia of the adipose tissue. Glucocorticoids also have acute antilipolytic effect on adipocytes, whereas their genomic actions facilitate increased lipolysis after about 48 hours of exposure. The acute and long-term effects of GCs on adipose tissue lipolysis remain unclear. Although considerable evidence supports the notion that GCs increase lipolysis through glucocorticoid-induced increases of lipase expression, they clearly have antilipolytic effects within these same tissues and cell line models. 相似文献
20.
E. Hagström-Toft P. Arner U. Johansson L. S. Eriksson U. Ungerstedt J. Bolinder 《Diabetologia》1992,35(7):664-670
Summary The effects of insulin, and its interactions with catecholamines through beta-adrenoceptors, on human adipose tissue glucose utilization and lipolysis were investigated in vivo. Microdialysis of the extracellular compartment of abdominal subcutaneous adipose tissue was performed in healthy subjects of normal weight, before and during a 2-h hyperinsulinaemic (61±3 mU/l), euglycaemic clamp. The tissue was perfused with or without the beta-adrenergic agonist isoproterenol (10–mol/l), and the tissue dialysate concentrations of glucose, glycerol (lipolysis index) lactate and pyruvate were determined. During the insulin infusion, glucose in adipose tissue decreased by 20% (p<0.001), despite arterial steady-state normoglycaemia. The concentrations of lactate and pyruvate increased gradually to a steadystate plateau of twice the basal level in adipose tissue and arterial blood. Insulin-induced suppression of glycerol (lipolysis index) was, if anything, more marked in adipose tissue than in plasma (65% vs 50% decrease from baseline levels, p<0.05). In situ perfusion of adipose tissue with isoproterenol, starting either at the beginning of the study period or at 45 min after initiation of the insulin infusion, resulted in marked and rapid elevations of all the investigated metabolites in the adipose tissue extracellular compartment (p<0.05–0.005).Itis concluded that insulin action on glucose uptake and lipolysis in human adipose tissue in vivo is counteracted by beta-adrenoceptor stimulation. In contrast, insulin and beta-adrenoceptors have synergistic effects on non-oxidative glucose metabolism in human adipose tissue in situ. 相似文献