Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.79 (hormone-sensitive lipase)
2,163 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The enzymes lipoprotein lipase (LPL, EC 3.1.1.34) and hormone-sensitive lipase (HSL, EC 3.1.1.3) apparently catalyze opposing functions in white adipose tissue: the former is concerned with fat storage, the latter with fat mobilization. We have studied their regulation in vivo in normal subjects in the postabsorptive state and after eating meals of different compositions, by measurement of arteriovenous concentration differences for triacylglycerol, non-esterified fatty acids and glycerol across a subcutaneous adipose depot. The two enzymes are regulated in a broadly reciprocal manner: in the overnight-fasted state, HSL is more active, but after a meal HSL is suppressed whilst LPL is activated. The movement of fatty acids in and out of adipose tissue appears to be driven by concentration gradients generated by regulation of these two enzymes, and also by activation, in the postprandial period, of the process of fatty acid esterification. The results show some interesting and perhaps unexpected features of metabolic regulation. Of the fatty acids generated by the action of LPL on circulating TAG, a large proportion is released directly into the venous plasma: close to 100% in the overnight-fasted state, and 50% or more at the peak of LPL action after a meal, making what appear reasonable assumptions. We suggest that this apparent 'inefficiency' of fat storage reflects the energetic cost of maintaining precise control over such a fundamental process. Although LPL is usually thought of as the enzyme regulating fat deposition, in fact the fatty acids and glycerol it releases from circulating TAG represent a substantial proportion of those released from adipose tissue, especially in the postprandial state. In addition, although HSL is considered the enzyme responsible for fat mobilization, suppression of its activity is essential to normal regulation of fat deposition. Thus, fat storage and fat mobilization during normal daily life are controlled by coordinated regulation of a number of enzymatic processes in white adipose tissue.
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PMID:Coordinated regulation of hormone-sensitive lipase and lipoprotein lipase in human adipose tissue in vivo: implications for the control of fat storage and fat mobilization. 757 42

Female rats receiving alcohol (20%) in drinking water during lactation (AL) were compared to pair-fed animals (PF) and normal controls (C) fed ad lib. All animals were killed on the 12th day of lactation. When compared to C rats, food intake decreased in both AL and PF groups, and this effect was followed by a lower body weight and mammary gland (MG), liver, and parametrial adipose tissue weights. Mammary glands triacylglyceride concentration (TG) was much lower in PF than in AL, although in the latter, values did not reach those of C, and had higher liver TG concentration than any of the other groups. Both PF and AL rats had lower plasma TG, glycerol, and free fatty acid concentrations and higher beta-hydroxybutyrate concentration than C rats. When compared to C rats, the rate of lipogenesis in MG was higher in both PF and AL rats, whereas in liver it was higher in PF and lower in AL rats, and in adipose tissue it was higher in PF and unchanged in AL rats. The appearance of 14C lipids 4 h after oral [14]triolein in both MG and liver was lower in AL and PF rats and only lower in adipose tissue of AL rats as compared to the c rats. Lipoprotein lipase and hormone-sensitive lipase activities were lower in MG in both PF and AL rats than in C, whereas in adipose tissue the activity of lipoprotein lipase did not differ between AL and C rats and the activity of HSL was lower in the former. These findings therefore show that in spite of reduced uptake of orally administered triglycerides due to decreased LPL activity, maternal alcohol feeding during lactation in the rat preserves the mammary gland triglyceride content thanks to enhanced lipogenetic activity. On the other hand, it causes liver triglycerides accumulation, probably as a result of the decreased rate of triglycerides released into circulation, and these changes are not caused by the reduced food intake of the animals.
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PMID:Effects of ethanol intake on lipid metabolism in the lactating rat. 888 39

The adipocyte is a metabolically active cell that functions to store energy for times of energy deprivation or enhanced need. Obesity is characterized by increased lipid accumulation and turnover compared with the nonobese state. Both triglyceride synthesis and lipolysis are regulated metabolic processes in the adipocyte. Current research on the metabolic activities of the human adipocyte focus on plasma triglyceride hydrolysis and uptake of fatty acids by LPL, esterification of these fatty acids, and the subsequent triglyceride breakdown by hormone-sensitive lipase in response to stimulation of adrenergic receptors. These topics are discussed in relationship to the development of obesity.
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PMID:Fat cells. 897 49

The fat cell, the functional entity of adipose tissue, is mainly involved in energy storage and mobilization. The deposition of fat in, and the mobilization of fat from, adipose tissue are precisely controlled by enzyme activities: LPL and HSL. These functions are under control of hormones such as insulin, catecholamines and, to some extent, steroid hormones. The adipocytes have been recently identified as the source of many factors that may act like hormones either in the local environment or at distant sites, are also target cells for many more hormones. Adipose tissue metabolism varies from one region of the body to another. The metabolic activity is the lowest in the subcutaneous gluteofemoral area, followed by the abdominal subcutaneous area, and the highest in the visceral region. The metabolic activity of gluteofemoral fat is activated in lactating mothers. Body fat content changes with female age. Puberty, parity and menopause seems to increase accretion of adipose tissue. Obesity is defined as an increase in body fat content. There is general agreement that obesity develops as an interaction between a genetic susceptibility and environment which is expressed when the subject is exposed to a certain set of environmental conditions. Obesity develops when energy intake exceeds energy expenditure over a prolonged period. Excess body weight is associated with several diseases which can shorten life expectancy. The prevalence of obesity is high and increases steadily. Approximately 20-40% of women are overweight (BMI 25-30 kg/m-2) and 5-20% are obese (BMI > 30 kg/m-2).
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PMID:[Pathophysiological aspects of adipose tissue development in women]. 1089 89

It is well known that growth hormone (GH) treatment reduces fat mass (FM), which presumably is mediated through stimulation of triglyceride breakdown and inhibition of adipose tissue lipoprotein lipase activity (AT-LPL). However, it is unknown which of the 2 GH-regulated pathways are of most importance for the reduction in FM. We investigated the effect of weight loss together with GH treatment on the activity and gene expression of LPL and hormone-sensitive lipase (HSL) in AT and muscle tissue. A very-low-calorie diet ([VLCD] 740 kcal/d) was given to 18 obese women (body mass index [BMI] > 35 kg/m2) and half of them were treated with GH (0.04 IU/kg) for 4 weeks in a randomized double-blind placebo-controlled study. Subcutaneous fat and muscle biopsies were taken before and after 4 weeks. Weight loss after 4 weeks was similar in the 2 groups, with a reduction of 4.5% (placebo) and 4.6% (GH) and a reduction of FM by 7.4% and 9.0% ([NS] nonsignificant). The weight loss resulted in a small and NS reduction of AT-LPL activity by 20% +/- 12% in the placebo group, but in the GH group, AT-LPL was significantly reduced by 65% +/- 8% (P < .01). Muscle LPL (M-LPL) activity was not affected by the weight loss alone, but a significant reduction was observed in the GH group (20.4% +/- 10%, P < .05). AT-HSL activity was significantly enhanced after weight loss, but GH had no additional effect on this minor increment. This is in accordance with the finding that the increment in free fatty acid (FFA) after weight loss was similar in the 2 groups. GH treatment was associated with a significant reduction of high-density lipoprotein (HDL) cholesterol (P < .05). In conclusion, GH significantly inhibited AT-LPL activity but had no additional effect on the hypocaloric-induced loss of FM, indicating that under such circumstances, AT-LPL does not directly regulate adipose tissue mass. GH was not found to have opposite effects on the activity of LPL in adipose tissue and muscle, since GH treatment reduced them both (by 65% and 20%, respectively). The VLCD-induced weight loss was associated with a minor enhanced activity of AT-HSL with no independent effect of GH. Thus, concerning body weight, FM, and lipolytic activity, treatment with GH offers no extra benefits during a VLCD for 4 weeks.
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PMID:Regulation of lipoprotein lipase and hormone-sensitive lipase activity and gene expression in adipose and muscle tissue by growth hormone treatment during weight loss in obese patients. 1091 3

Obesity is a chronic metabolic disorder associated with CVD and increased morbidity and mortality. When the BMI is > or = 30 kg/m2, mortality rates from all causes, and especially CVD, are increased by 50% to 100%. There is strong evidence that weight loss in overweight and obese individuals improves risk factors for diabetes and CVD. Additional evidence indicates that weight loss and the associated diuresis reduce blood pressure in both overweight hypertensive and nonhypertensive individuals, reduce serum TG levels, increase high-density lipoprotein cholesterol levels, and may produce some reduction in low-density lipoprotein cholesterol concentrations. Of interest, even if weight loss is minimal, obese individuals showing a good level of cardiorespiratory fitness are at reduced risk for cardiovascular mortality than lean but poorly fit subjects. Insulin and catecholamines have pronounced metabolic effects on human adipose tissue metabolism. Insulin stimulates LPL and inhibits HSL; the opposite is true for catecholamines. There is regional variation in adipocyte TG turnover favoring lipid mobilization in the visceral fat depots and lipid storage in the peripheral subcutaneous sites. The hormonal regulation of adipocyte TG turnover is altered in obesity and is most marked in central obesity. There is resistance to insulin stimulation of LPL; however, LPL activity in fasted obese subjects is increased and remains so following weight reduction. Catecholamine-induced lipolysis is enhanced in visceral fat but decreased in subcutaneous fat. Numerous adaptive responses take place with physical training. These adaptations result in a more efficient system for oxygen transfer to muscle, which is now able to better utilize the unlimited lipid stores instead of the limited carbohydrate reserves available. In addition, the reduced adipose tissue mass represents an important mechanical advantage, allowing better long-term work. Gender differences have been reported in the adaptation of adipose tissue metabolism to aerobic exercise training. Physical training helps counteract the permissive and affluent environment that predisposes reduced-obese subjects to regain weight. An exercise program using weight resistance modalities may also be included safely, and it improved program retention in a multidisciplinary weight management program that was designed for obese children. Thirty to 45 minutes of physical activity of moderate intensity, performed 3 to 5 days a week, should be encouraged. All adults should set a long-term goal to accumulate at least 30 minutes or more of moderate-intensity physical activity on most, and preferably all days. Public health interventions promoting walking are likely to be the most successful. Indeed, walking is unique because of its safety, accessibility, and popularity. It is noteworthy that there is a clear dissociation between the adaptation of cardiorespiratory fitness and the improvements in the metabolic risk profile that can be induced by endurance training programs. It appears that as long as the increase in energy expenditure is sufficient, low-intensity endurance exercise is likely to generate beneficial metabolic effects that would be essentially similar to those produced by high-intensity exercise. The clinician should therefore focus on the improvement of the metabolic profile rather than on weight loss alone. Realistic goals should be set between the clinician and the patient, with a weight loss of approximately of 0.5 to 1 pound per week. It should be kept in mind that since it generally takes years to become overweight or obese, a weight loss pattern of 0.5 or 1 pound per week will require time and perseverance to reach the proposed target. However, the use of physical activity as a method to lose weight seems inversely related to patients' age and BMI and directly related to the level of education. Thus, public health interventions helping these groups to become physically active remain a challenge and further emphasize the importance of the one-on-one interaction between the clinician/health care professional with the obese individual "at risk" of CVD. This notion is critical, as it has been shown that less than half of obese adults have reported being advised to lose weight under the guidance of health care professionals.
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PMID:Exercise in weight management of obesity. 1157 Jan 17

We sought to investigate the influence of 17beta-estradiol (E(2)) on key enzymes of lipogenesis and lipolysis in subcutaneous (SC) abdominal adipocytes isolated from women. In addition, we wished to determine the influence of an anti-estrogen, ICI:compound 182,780 (anti-E), known to act via the estrogen receptor (ER), alone and in combination with E(2). Adipose tissue was obtained from 17 women undergoing elective surgery, with a mean age of 47 years (range, 34 to 62), mean weight of 65.4 kg (range, 58.1 to 75.0), and mean body mass index (BMI) of 25 kg/m(2) (range, 22 to 27). Isolated adipocytes were treated with varying doses of E(2), anti-E, or E(2) in combination with anti-E 10(-8) mol/L for 48 hours. Following treatment, proteins were extracted and the effects on lipogenesis and lipolysis were assessed, using Western blotting to determine the relative expression of the key enzymes of these processes, lipoprotein lipase (LPL; 56 kd), and hormone-sensitive lipase (HSL; 84 kd), respectively. Glycerol release into the medium was also measured as an index of lipolytic activity. The protein expression studies demonstrated that E(2) altered expression of LPL relative to control, with the highest dose significantly reducing LPL expression and the lower doses significantly increasing LPL expression (mean protein expression relative to control +/- SE): E(2) 10(-12) mol/L, 1.79 +/- 0.16 (P <.001); E(2) 10(-7) mol/L, 0.56 +/- 0.08 (P <.05). In contrast, HSL expression was increased relative to control at the higher doses of E(2) but was not significantly altered relative to control at the lower doses: E(2) 10(-12) mol/L, 1.02 +/- 0.14 (P >.05); E(2) 10(-7) mol/L, 1.55 +/- 0.17 (P <.01). Anti-E 10(-8) mol/L alone reduced LPL protein expression relative to control (P <.05) and increased HSL protein expression relative to control (P >.05). In combination with E(2) 10(-7) mol/L, anti-E 10(-8) mol/L did not abrogate the inhibitory effect on LPL expression relative to control (P <.05). Furthermore, E(2) 10(-7) mol/Lin combination with anti-E 10(-8) mol/L, displayed a stimulatory effect on HSL expression relative to control (P <.01). Glycerol release studies following the higher doses of E(2), and also following E(2) 10(-7) mol/L in combination with anti-E 10(-8) mol/L, provided support for the HSL protein expression studies. We conclude that the highest concentration of E(2) (10(-7) mol/L) significantly reduced LPL expression relative to control, while the lower concentrations significantly increased LPL expression relative to control. The highest concentration of E(2) also significantly increased both HSL expression and glycerol release relative to control. The effects of anti-E suggest that the in vitro effects of E(2) on lipogenesis and lipolysis occur, at least in part, through a receptor-mediated pathway. In addition, as recently observed in other tissues, ICI:compound 182,780 does not appear to behave as a pure anti-estrogen in isolated human adipocytes.
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PMID:17Beta-estradiol and anti-estrogen ICI:compound 182,780 regulate expression of lipoprotein lipase and hormone-sensitive lipase in isolated subcutaneous abdominal adipocytes. 1270 Oct 46

It was hypothesized that transcriptional reprogramming is involved in the structural and functional adaptations of lipid metabolism in human tibialis anterior muscle (TA) from endurance-trained male subjects. RT-PCR experiments demonstrated a significant upregulation of the mRNA level of key enzymes involved in 1) lipolytic mobilization of fatty acids (FA) from intramyocellular lipid (IMCL) stores via hormone-sensitive lipase (LIPE), 2) intramyocellular FA transport via muscle fatty acid binding protein (FABP3), and 3) oxidative phosphorylation (cytochrome c oxidase I, COI), in TA of endurance-trained vs. untrained subjects. In contrast, mRNAs for factors involved in glycolysis (muscle 6-phosphofructokinase, PFKM), intramyocellular storage of FA (diacylglycerol O-acyltransferase 1, DGAT), and beta-oxidation (long-chain acyl-coenzyme A dehydrogenase, ACADL) were invariant between TA of trained and untrained subjects. Correlation analysis identified an association of LIPE with FABP3 and LPL (lipoprotein lipase) mRNA levels and indicated coregulation of the transcript level for LIPE, FABP3, and COI with the level of mRNA encoding peroxisome proliferator-activated receptor-alpha (PPAR-alpha), the master regulator of lipid metabolism. Moreover, a significant correlation existed between LPL mRNA and the absolute rate of IMCL repletion determined by magnetic resonance spectroscopy after exhaustive exercise. Additionally, the LIPE mRNA level correlated with ultrastructurally determined IMCL content and mitochondrial volume density. The present data point to a training-induced, selective increase in mRNA levels of enzymes which are involved in metabolization of intramuscular FA, and these data confirm the well-established phenomenon of enhanced lipid utilization during exercise at moderate intensity in muscles of endurance-trained subjects.
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PMID:Transcriptional adaptations of lipid metabolism in tibialis anterior muscle of endurance-trained athletes. 1456 68

To investigate the mechanism of difference in intramuscular fat deposition between Erhualian and Large White pigs,single tube relative-quantitative RT-PCR method was used to investigate the development patterns of lipogenic (ACX, LPL, ME) and lipolytic (HSL) gene expression with 18S internal standard control. Sixteen Large White boars and twenty Erhualian boars were selected and raised according to normal nutrition standard respectively. The animals were selected randomly and slaughtered at 15 kg, 40 kg, 60 kg and 90 kg for Large White pigs and at 18 kg, 40 kg, 60 kg, 80 kg and 90 kg for Erhualian pigs respectively; with four animals of each breed at each time. The supraspinatus and semimembranosus muscles were removed for total RNA extraction and longisimus dorsi muscle for intramuscular fat (IMF) analysis using ether extract method. The results showed: (1) The property of IMF between Erhualian and Large White boars was similar during early growing period (before 40 kg) (P > 0.05) ,thereafter, IMF level of Erhualian boars increased dramatically to 4% at 60 kg and over 5% at 90 kg while Large White boars kept steadily at about 2% (P < 0.05); (2) The pattern of lipogenic and lypolytic gene expression was similar between semimembranosus and supraspinatus muscle in each breed; (3) The tendency for LPL and ME mRNA expression coincided with that of IMF development among 20 approximately 60 kg in Erhualian pigs. The results suggest that the development of IMF between 20 kg and 60 kg in Erhualian pigs may play a meaningful role in deposition of IMF,and that the expression of ME and LPL mRNA may contribute to fast sediment of IMF in Erhualian pigs.
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PMID:[Comparative study on lipogenic and lipolytic gene expression in intramuscular fat tissue between growing Erhualian and large white pigs]. 1565 73

Colonic resection leads to insulin resistance, but the mechanisms are unknown. We used an integrated approach to examine adipose tissue and skeletal muscle metabolism in patients lacking a colon. Ten healthy colectomized patients having undergone surgery for ulcerative colitis and 10 matched control subjects were studied with a hyperinsulinemic-euglycemic clamp to measure insulin sensitivity, an arteriovenous sampling meal tolerance study to measure postprandial substrate flux across adipose tissue and skeletal muscle, and adipose tissue and skeletal muscle biopsies to quantify the expression of genes involved in glucose and lipid metabolism. Colectomized subjects exhibited lower insulin sensitivity (homeostatic model assessment model, 33% reduction, P = 0.03; minimal model, 29% reduction, P = 0.05), elevated aldosterone (9-fold, P = 0.003), leptin (2.2-fold, P = 0.03), and an increased rate of nonesterified fatty acid and glycerol release from adipose tissue (P = 0.02) especially in the late postprandial period. The uptake of fatty acids into muscle was also significantly increased (P = 0.007), as were muscle CD36 and LPL mRNA expression compared with controls. In adipose tissue, hormone-sensitive lipase mRNA expression was increased (P = 0.015), whereas peroxisome proliferator-activated receptor-gamma expression was decreased (P = 0.02), as was that of CD36 (P = 0.001). In this study, alterations in fatty acid metabolism after colonic resection altered may have contributed to the impairment of insulin sensitivity.
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PMID:Enhanced metabolic cycling in subjects after colonic resection for ulcerative colitis. 1571 5


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