Hormone-sensitive Lipase mRNA Levels Research Articles

Effects of Weight Loss and Aerobic Exercise Training on Adi-Pose Tissue Zinc α2-Glycoprotein and Associated Genes in Obesity.

Zinc α2-glycoprotein (ZAG) has been implicated in fatty acid metabolism and utilization and is lower in obese and higher in cachexic adults compared to those of normal weight. Previous studies suggest that ZAG binds to the beta3-adrenergic receptor (β3AR) to influence fatty acid metabolism in adipose tissue by regulating hormone sensitive lipase (HSL). The purpose of this study is to investigate the effects of a six-month weight loss (WL) or aerobic exercise (AEX) intervention on adipose tissue and skeletal muscle ZAG mRNA levels and protein expression, as well as the expression of β3AR, and HSL. Abdominal adipose tissue (AB) and gluteal adipose tissue (Glut) and vastus lateralis muscle biopsies were performed before and after WL (n = 13) or AEX (n = 13). ZAG, HSL, and β3AR expressions were determined by RT-PCR, and ZAG and HSL plasma levels by ELISA. Body weight decreased by 9.69% (p < 0.001) in WL and did not change with AEX. Maximal oxygen consumption (VO2max) increased by 7.1% (p < 0.005) after WL and by 16.69% (p < 0.001) after AEX. WL significantly decreased body weight with a reduction of percentage of fat, fat mass, fat-free mass (FFM). AEX decreased percent fat and increased VO2max, but did not change fat mass and FFM. Abdominal ZAG and HSL mRNA levels did not change significantly after WL or AEX. There were no changes in plasma ZAG, HSL and adipose tissue β3AR mRNA levels after WL and AEX. ZAG, HSL and β3AR mRNA expressions in adipose tissue are positively associated each other. Adipose tissue abdominal and gluteal HSL are negatively associated with HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), and both ZAG and HSL adipose tissue are negatively associated with fasting glucose and the glucose area under the curve. Further work is needed to elucidate the role of ZAG and HSL in the propensity for weight gain and the ability of exercise to mitigate these responses.

Effect of dietary copper addition on lipid metabolism in rabbits

ABSTRACTThe present study was conducted to investigate the effect of copper supplementation on lipid metabolism in rabbits. Our study showed dietary copper addition (5-45 mg/kg) increased body mass gain, but decreased fat and liver weights compared with those in the control group (P < 0.05). Copper (45 mg/kg) addition significantly increased the skeletal muscle weight, but inhibited cytoplasmic lipid accumulation in liver, skeletal muscle and adipose tissue (P < 0.05). Compared with the control group, dietary copper addition (45 mg/kg) significantly increased plasma triglyceride levels but decreased very low density lipoprotein levels (P < 0.05). Copper treatment significantly increased gene expression of carnitine palmitoyltransferase (CPT) 1, CPT2 and peroxisome proliferator-activated receptor (PPAR) a in liver (P < 0.05). In skeletal muscle, CPT1, CPT2, fatty acid transport protein, fatty acid-binding protein, and PPARa mRNA as well as phosphorylated AMP-activated protein kinase (AMPK) levels were significantly up-regulated by copper treatment (P < 0.05). Rabbits receiving copper supplementation had higher CPT1, CPT2, PPARa and hormone-sensitive lipase mRNA levels in adipose tissue (P < 0.05). In conclusion, copper promoted skeletal muscle growth and reduced fat accretion. PPARa signaling in liver, skeletal muscle and adipose tissues and AMPK signaling in skeletal muscle tissue were involved in the regulation of lipid metabolism by copper.

Different effects of growth hormone and fasting on the induction patterns of two hormone-sensitive lipase genes in red seabream Pagrus major

Growth hormone (GH) increases phosphorylation and mRNA levels of hormone-sensitive lipase (HSL) in the livers of some marine teleosts. The hepatic GH-HSL axis appears to play important roles in fasting-induced lipolysis. However, it is not known whether GH exerts similar effects on HSL in fish adipose tissues. Functional differentiation of two fish-specific HSL isoforms (HSL1 and HSL2) also remains unclear. The present study seeks to address two unanswered questions about fish lipolysis using red seabream (Pagrus major): (1) Does GH increase phosphorylation and mRNA levels of HSL in adipose tissue? (2) How do GH and fasting affect mRNA levels of two HSL isoform genes in the liver and adipose tissue? To this end, we first cloned HSL1 and HSL2 cDNAs and investigated their tissue distribution. Transcripts of both HSLs and HSL1 proteins were abundant in the visceral adipose tissue, gonads, and liver, suggesting the important role of HSL in adipose tissue lipolysis. HSL2 transcript levels were 20–65% those of HSL1 except in the skin, and HSL2 proteins were not detected by our in-house antisera. Ex vivo administration of GH increased HSL1 phosphorylation, non-esterified fatty acid (NEFA) release, and levels of HSL1 and HSL2 mRNA in both the liver and visceral adipose tissue. Hepatic HSL2 mRNA was particularly sensitive to GH administration and sometimes exceeded HSL1 mRNA levels with up to 13-fold induction. In contrast, fasting for 4 and 7d increased HSL1 mRNA levels, but had only marginal effects on HSL2 mRNA levels in both adipose tissue or liver. We concluded that GH would increase HSL mRNAs during adipose tissue lipolysis in red seabream; however, GH and fasting result in different induction ratio of two HSL isoform genes, suggesting that other hormone(s) also contributes to fasting-induced lipolysis.

Fatty acid composition and mRNA expression levels of lipid-metabolic genes in the muscles of ovariectomised young goats

This study investigated the fatty acid composition and mRNA levels of acetyl-coenzyme A carboxylase (ACC), fatty acid synthase (FAS), hormone-sensitive lipase (HSL) and lipoprotein lipase (LPL) genes in the Longissimus dorsi muscle (LD) and Biceps femoris muscle (BF) of nine ovariectomised young goats, 50 days after ovariectomy at 5 months of age, relative to nine Control goats. Ovariectomy resulted in faster growth rates (130 vs 110 g/days; P = 0.027), more intramuscular fat (3.37% vs 1.62%; P = 0.009) and heavier final weights (28.3 vs 26.6 kg; P = 0.035). The total saturated fatty acid, C15:0 in the LD and C6:0, C11:0, C12:0, C15:0 and C21:0 in the BF were lower in ovariectomised goats than that in the Control goats (P &lt; 0.05). Ovariectomy increased the total monounsaturated fatty acids in the LD (P &lt; 0.05) and BF (P &lt; 0.01). In the BF, the total polyunsaturated fatty acids and C18:2 of ovariectomised goats were lower than those of the Control goats (P &lt; 0.05), and the C20:2 content significantly decreased in the LD (P &lt; 0.05). The LD of the ovariectomised goats expressed significantly higher FAS but lower HSL mRNA levels than those of Control goats (P &lt; 0.01). Significantly higher ACC, FAS and LPL and lower HSL mRNA levels were observed in the BF of the ovariectomised goats than in the BF of Controls (P &lt; 0.05). These data suggest that ovariectomy affects fatty acid composition potentially by altering the expression of lipid-metabolic genes in the muscles of young goats.

FNDC5 overexpression and irisin ameliorate glucose/lipid metabolic derangements and enhance lipolysis in obesity

Irisin is a cleaved and secreted fragment of fibronectin type III domain containing 5 (FNDC5), and contributes to the beneficial effects of exercise on metabolism. Here we report the therapeutical effects of FNDC5/irisin on metabolic derangements and insulin resistance in obesity, and show the lipolysis effect of irisin and its signal molecular mechanism. In obese mice, lentivirus mediated-FNDC5 overexpression enhanced energy expenditure, lipolysis and insulin sensitivity, and reduced hyperlipidemia, hyperglycemia, hyperinsulinism, blood pressure and norepinephrine levels; it increased hormone-sensitive lipase (HSL) expression and phosphorylation, and reduced perilipin level and adipocyte diameter in adipose tissues. Subcutaneous perfusion of irisin reduced hyperlipidemia and hyperglycemia, and improved insulin resistance. Either FNDC5 overexpression or irisin perfusion only induced a tendency toward a slight decrease in body weight in obese mice. In 3T3-L1 adipocytes, irisin enhanced basal lipolysis rather than isoproterenol-induced lipolysis, which were prevented by inhibition of adenylate cyclase or PKA; irisin increased the HSL and perilipin phosphorylation; it increased PKA activity, and cAMP and HSL mRNA levels, but reduced perilipin expression. These results indicate that FNDC5/irisin ameliorates glucose/lipid metabolic derangements and insulin resistance in obese mice, and enhances lipolysis via cAMP–PKA–HSL/perilipin pathway. FNDC5 or irisin can be taken as an effective therapeutic strategy for metabolic disorders.

Green tea catechins enhance norepinephrine-induced lipolysis via a protein kinase A-dependent pathway in adipocytes

Green tea catechins have been shown to attenuate obesity in animals and humans. The catechins activate adenosine monophosphate-activated protein kinase (AMPK), and thereby increase fatty acid oxidation in liver and skeletal muscles. Green tea catechins have also been shown to reduce body fat in humans. However, the effect of the catechins on lipolysis in adipose tissue has not been fully understood. The aim of this study was to clarify the effect of green tea catechins on lipolysis in adipocytes and to elucidate the underlying mechanism. Differentiated mouse adipocyte cell line (3T3-L1) was stimulated with green tea catechins in the presence or absence of norepinephrine. Glycerol and free fatty acids in the media were measured. Phosphorylation of hormone-sensitive lipase (HSL) was determined by Western blotting, and the mRNA expression levels of HSL, adipose triglyceride lipase (ATGL), and perilipin were determined by quantitative RT-PCR. The cells were treated with inhibitors of protein kinase A (PKA), protein kinase C (PKC), protein kinase G (PKG), or mitogen-activated protein kinase (MAPK) to determine the responsible pathway. Treatment of 3T3-L1 adipocytes with green tea catechins increased the level of glycerol and free fatty acids released into the media in the presence, but not absence, of norepinephrine, and increased the level of phosphorylated HSL in the cells. The catechins also increased mRNA and protein levels of HSL and ATGL. PKA inhibitor (H89) attenuated the catechin-induced increase in glycerol release and HSL phosphorylation. The results demonstrate that green tea catechins enhance lipolysis in the presence of norepinephrine via a PKA-dependent pathway in 3T3-L1 adipocytes, providing a potential mechanism by which green tea catechins could reduce body fat.

Effects of resveratrol on lipid metabolism in muscle and adipose tissues: A reevaluation in a pig model

The body fat-lowering effect and mechanisms of action of resveratrol (0, 300, 600 mg resveratrol/kg diet) was evaluated in a pig model. Resveratrol improved serum lipid profiles, and decreased visceral adipose tissue weight and serum leptin level. In adipose tissue, peroxisome proliferator activated receptor γ (PPARγ) and fatty acid synthase (FAS) mRNA levels, and FAS and lipoprotein lipase (LPL) activities were decreased by resveratrol, while hormone sensitive lipase (HSL), adipose triglyceride lipase (ATGL) and carnitine palmitoyl transferase-1(CPT-1) mRNA levels, and HSL and CPT-1 activities were increased. In muscle tissue, PPARγ, FAS, acetyl-CoA carboxylase (ACC) and LPL mRNA levels and FAS and ACC activities were decreased by resveratrol, while HSL mRNA levels and CPT-1 activity were increased. Moreover, compared with the control group, LPL activity was decreased, and CPT-1 mRNA levels and HSL activity were increased in the 600 mg resveratrol/kg diet group. This study provides the very first evidence in a pig model that resveratrol could improve serum lipid profiles and decrease body fat deposition, which might be mediated by a reduction in fatty acid uptake and de novo lipogenesis, as well as an increase in fat mobilization and fatty acid oxidation in muscle and adipose tissues.

Supplementation dietary zinc levels on growth performance, carcass traits, and intramuscular fat deposition in weaned piglets.

This study was conducted to estimate dietary zinc (Zn) levels on growth performance, carcass traits, and intramuscular fat (IMF) deposition in weaned piglets. Sixty piglets were randomly divided into five groups, as follows: control (basal diet), Zn250, Zn380, Zn570, and Zn760 with supplementation of 250, 380, 570, and 760 mg Zn/kg of the basal diet, respectively. The final weight, average daily gain (ADG), gain/feed (G/F), lean meat percentage, fat meat percentage, lean eye area, backfat thickness, and IMF content were dose-dependently increased in all groups of Zn treatment. The serum total triglycerides (TG) and free fatty acid (FFA) were significantly higher in all Zn treatments than in the control. The enzyme activities of lipoprotein lipase (LPL), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) were markedly higher, while enzyme activities of hormone-sensitive lipase (HSL) and carnitine palmitoyltransferase-1 (CPT-1) were significantly lower in all Zn treatments than in the control. The messenger RNA (mRNA) levels of sterol regulatory element-binding protein 1 (SREBP-1), stearoyl-CoA desaturase (SCD), FAS, ACC, peroxisome proliferator-activated receptor γ (PPARγ), LPL, and adipocyte fatty acid-binding protein (A-FABP) were significantly higher, while the mRNA levels of CPT-1 and HSL were significantly lower in all Zn treatments compared with the control. These results indicated that high levels of Zn increased IMF accumulation by up-regulating intramuscular lipogenic and fatty acid transport gene expression and enzyme activities while down-regulating lipolytic gene expression and enzyme activities.

Breed difference of porcine Sirtuin 1, adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL)

In the current study, we investigated the breed difference of Sirt1 gene expression in liver and pancreas between Jinhua pigs (a local fatty breed of China) and Landrace (a leaner breed). In addition, the gene expression of lipid metabolism enzymes adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL) has also been examined. Results showed that the serum triglyceride (TG), and total cholesterol (TCHO) concentration of Jinhua pigs were greater than Landrace while the serum glycerol in Jinhua pigs was lower at the age of 180d. The serum leptin concentration was also greater in Jinhua pigs. Compared with Landrace, the mRNA level and protein abundance of Sirt1 were lower both in liver and pancreas in Jinhua pigs. Consistent with Sirt1 expression, in liver and pancreas, the mRNA expression of lipolitic enzymes ATGL and HSL was always lower in Jinhua pigs than Landrace respectively. Furthermore, similar results were found in 60d pigs. The mRNA levels of Sirt1, ATGL and HSL were decreased in 60d Jinhua pigs comparatively. These results indicated that porcine Sirt1, as well as ATGL and HSL gene expressions are different between fatty and leaner pigs. This will provide useful information for better known of Sirt1 function in fat deposition.

Palmitoleic acid (n-7) increases white adipocyte lipolysis and lipase content in a PPARα-dependent manner

We investigated whether palmitoleic acid, a fatty acid that enhances whole body glucose disposal and suppresses hepatic steatosis, modulates triacylglycerol (TAG) metabolism in adipocytes. For this, both differentiated 3T3-L1 cells treated with either palmitoleic acid (16:1n7, 200 μM) or palmitic acid (16:0, 200 μM) for 24 h and primary adipocytes from wild-type or PPARα-deficient mice treated with 16:1n7 (300 mg·kg(-1)·day(-1)) or oleic acid (18:1n9, 300 mg·kg(-1)·day(-1)) by gavage for 10 days were evaluated for lipolysis, TAG, and glycerol 3-phosphate synthesis and gene and protein expression profile. Treatment of differentiated 3T3-L1 cells with 16:1n7, but not 16:0, increased basal and isoproterenol-stimulated lipolysis, mRNA levels of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) and protein content of ATGL and pSer(660)-HSL. Such increase in lipolysis induced by 16:1n7, which can be prevented by pharmacological inhibition of PPARα, was associated with higher rates of PPARα binding to DNA. In contrast to lipolysis, both 16:1n7 and 16:0 increased fatty acid incorporation into TAG and glycerol 3-phosphate synthesis from glucose without affecting glyceroneogenesis and glycerokinase expression. Corroborating in vitro findings, treatment of wild-type but not PPARα-deficient mice with 16:1n7 increased primary adipocyte basal and stimulated lipolysis and ATGL and HSL mRNA levels. In contrast to lipolysis, however, 16:1n7 treatment increased fatty acid incorporation into TAG and glycerol 3-phosphate synthesis from glucose in both wild-type and PPARα-deficient mice. In conclusion, palmitoleic acid increases adipocyte lipolysis and lipases by a mechanism that requires a functional PPARα.

The ratio of estrogen receptor α to β is associated with the expression of lipoprotein lipase and hormone-sensitive lipase in human adipose tissue

Lipoprotein lipase (LPL) is a key enzyme regulating fat metabolism by catabolizing plasma triglyceride (TG) into free fatty acid (FFA) (lipogenesis). Hormone-sensitive lipase (HSL) is rate-limiting enzyme for lipolysis by hydrolysis of stored TG in fat into FFA and glycerol. Current evidence has suggested that estrogen have regulatory effect on determining the amount and distribution of adipose tissue, but the mechanism remains unclear. Estrogen performs its biological activities through binding to its two receptors, ER-alpha (ERα) and ER-beta (ERβ), which are expressed in adipocytes. In this study, we investigate the association between ER expression and LPL or HSL in human adipose tissue. Exploratory, pilot study. We obtained small pieces (5-10g) of subcutaneous and omental adipose tissue from thirty-eight women who have had a gynecologic surgery. Total RNA was extracted from the fat samples, and a real-time RT-PCR was performed to measure and quantify the mRNA expression of ER, LPL, and HSL. Correlation and regression tests were performed for the variables. All subjects were premenopausal women aged 20 to 50 (median age: 39.2 years-old). In subcutaneous fat, neither ERα nor ERβ showed a correlation with the mRNA levels of LPL or HSL. However, the ER ratio (α/β) showed a negative correlation with the HSL (r = -0.553, P < 0.001). In omental fat, the mRNA of ERα was significantly correlated with both LPL and HSL (P = 0.001 and P = 0.017). In addition, the ER ratio was positively correlated with LPL mRNA level (r = 0.471, P < 0.001). The results of present study showed that both subtypes of ER were associated with the expression of LPL or HSL. Our findings imply that the ratio of ERα to ERβ in human subcutaneous and omental adipose tissue is an important regulatory factor involved in fat metabolism by interacting with LPL and HSL.

Hormone-sensitive lipase – quantitation of enzyme and mRNA in small biopsies of human adipose tissue

Hormone-sensitive lipase (HSL) activity was first identified as an adrenaline-sensitive lipolytic activity in adipose tissue. Hormonal activation of HSL occurs via cAMP-dependent protein kinase, which phosphorylates HSL. HSL is the enzyme responsible for the release of free fatty acids (FFAs) from adipose tissue and, therefore, plays a pivotal role in providing the major source of energy for most tissues. Although its expression is highest in adipose tissue, HSL is also expressed in the adrenal glands, ovaries, testes and, to a lesser extent, in skeletal and cardiac muscle and macrophages. The aim of this article is to describe a modified method of determination of HSL activity and gene expression in 10 mg of frozen human adipose tissue samples obtained by biopsy. The enzymes were extracted from the frozen tissue and activity was tested against a fatty acid-labelled diacylglycerol emulsion. The released fatty acids were extracted using a liquid–liquid partition system. The mean±standard error of the mean (SEM) HSL activity in normal fasting individuals was 2.38±0.75 milliunits (mU) oleate/min/g at 37°C. HSL mRNA levels were assessed in 10 mg of adipose tissue using a competitive reverse transcriptase polymerase chain reaction (RT-PCR) assay and the mean ratio of HSL mRNA molecules to β2-microglobulin-mRNA molecules in normal individuals was 0.29±0.04 (mean±SEM). The methods described here are suitable for use in adipose tissue biopsies obtained from normal individuals and provide a means for the examination of the regulation of this enzyme. The importance of this is becoming increasingly apparent, as the inability to suppress lipolysis is associated with conditions of insulin resistance and an increase in propensity to atherosclerosis. This is associated with inappropriate release of FFAs in the postprandial period, resulting in reduced sensitivity of glucose metabolism and increased postprandial lipaemia.

Standardized Ethanol Extract of Curcuma longa L. Fermented by Aspergillus oryzae Promotes Lipolysis via Activation of cAMP-Dependent PKA in 3T3-L1 Adipocytes

We investigated the effect of standardized ethanol extract from Curcuma longa L. fermented by Aspergillus oryzae (FTE) on lipid accumulation and lipolysis using 3T3-L1 adipocytes. Treatment with FTE at 100 μg/mL significantly reduced lipid accumulation by 43% as quantified by Oil Red O dye and microscopic observation. Intracellular triglyceride content was also lowered by 60%. To determine the effects of FTE on lipolysis, levels of glycerol release and mRNA expression of lipases were measured. Incubation of 3T3-L1 adipocytes with 60 and 100 μg/mL FTE dramatically elevated levels of free glycerol released into the medium by 58 and 77%, respectively. Likewise, treatment of mature adipocytes with FTE significantly increased cAMP level by reduction of phosphodiestersae-3B. Subsequently, FTE clearly increased hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) mRNA levels and decreased perilipin mRNA level via cAMP-dependent protein kinase A (PKA), resulting in lipolysis. Practical Applications Turmeric (the common name for Curcuma longa L.) is an Indian spice derived from rhizomes of the plant Curcuma longa, a perennial member of the Zingiberaceae family cultivated in India and other parts of Southeast Asia. Turmeric has traditionally been used for the treatment of inflammation, menstrual disorders, dyspepsia, vomiting and cancer. In this study, FTE suppressed 3T3-L1 preadipocyte differentiation and promoted lipolysis via upregulation of mRNA levels of HSL and ATGL by PKA phosphorylation. Our results suggested that FTE could be a candidate for antiobesity treatment through reduction of lipid accumulation and stimulation of lipolysis.

Fat-reducing effects of dehydroepiandrosterone involve upregulation of ATGL and HSL expression, and stimulation of lipolysis in adipose tissue

Dehydroepiandrosterone (DHEA) reduces body fat in rodents and humans, and increases glycerol release from isolated rat epididymal adipocytes and human visceral adipose tissue explants. It suggests that DHEA stimulates triglyceride hydrolysis in adipose tissue; however, the mechanisms underlying this action are still unclear.We examined the effects of DHEA on the expression of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), the key enzymes of lipolysis, in rat epididymal white adipose tissue (eWAT). Male Wistar rats were fed a diet containing 0.6% DHEA for 2weeks and eWAT was analyzed for mRNA and protein expression of ATGL and HSL, as well as mRNA expression of peroxisome proliferator-activated receptor γ 2 (PPARγ2) and its downstream target fatty acid translocase (FAT). Glycerol release from eWAT explants and serum free fatty acids (FFA) were also measured.Rats that received DHEA gained less weight, had 23% lower eWAT mass and 31% higher serum FFA levels than controls. Cultured explants of eWAT from DHEA-treated rats released 81% more glycerol than those from control rats. DHEA administration upregulated ATGL mRNA (1.62-fold, P<0.05) and protein (1.78-fold, P<0.05) expression as well as augmented HSL mRNA levels (1.36-fold, P<0.05) and Ser660 phosphorylation of HSL (2.49-fold, P<0.05). PPARγ2 and FAT mRNA levels were also increased in DHEA-treated rats (1.61-fold, P<0.05 and 2.16-fold, P<0.05; respectively). Moreover, ATGL, HSL, and FAT mRNA levels were positively correlated with PPARγ2 expression.This study demonstrates that DHEA promotes lipid mobilization in adipose tissue by increasing the expression and activity of ATGL and HSL. The effects of DHEA appear to be mediated, at least in part, via PPARγ2 activation, which in turn upregulates ATGL and HSL gene expression.

Effects of Dietary Energy Level on the Expression of the HSL Gene in Different Tissues of Sheep

A total of 36 four-mon-old hybrid lambs (Dorset×Thin-tailed Han sheep) with similar body weight (BW) were randomly allocated to three dietary treatments with different energy (7.21, 10.33 and 13.49 MJ d−1 ME) but similar protein levels. The animals were slaughtered and subcutaneous fat, longissimus dorsi muscle, femoral biceps muscle and cardiac muscle tissue samples were taken after being treated for 40 d. The samples were then subjected to quantitative PCR to determine mRNA expression of hormone-sensitive lipase (HSL) in different tissues in the laboratory. The findings showed that the abundance of HSL mRNA decreased with the elevation of dietary energy. In the subcutaneous fatty tissue, the HSL mRNA levels showed significant differences among the three groups (P<0.01); in the longissimus dorsi and femoral biceps muscles, the HSL mRNA level in the low energy group was significantly higher than that in the moderate and high energy groups (P<0.01). In the cardiac muscle, the HSL mRNA level in the moderate energy group was significantly different from the low and high energy groups (P<0.05). The number of HSL copies (Qty) in different tissues of sheep was different, it was greater in the subcutaneous fat than in longissimus dorsi muscle, femoral biceps muscle and heart.

Essential role of hormone-sensitive lipase (HSL) in the maintenance of lipid storage in Mycobacterium leprae-infected macrophages

Mycobacterium leprae (M. leprae), the causative agent of leprosy, parasitizes within the foamy or enlarged phagosome of macrophages where rich lipids accumulate. Although the mechanisms for lipid accumulation in the phagosome have been clarified, it is still unclear how such large amounts of lipids escape degradation. To further explore underlying mechanisms involved in lipid catabolism in M. leprae-infected host cells, we examined the expression of hormone-sensitive lipase (HSL), a key enzyme in fatty acid mobilization and lipolysis, in human macrophage THP-1 cells. We found that infection by live M. leprae significantly suppressed HSL expression levels. This suppression was not observed with dead M. leprae or latex beads. Macrophage activation by peptidoglycan (PGN), the ligand for toll-like receptor 2 (TLR2), increased HSL expression; however, live M. leprae suppressed this increase. HSL expression was abolished in the slit-skin smear specimens from patients with lepromatous and borderline leprosy. In addition, the recovery of HSL expression was observed in patients who experienced a lepra reaction, which is a cell-mediated, delayed-type hypersensitivity immune response, or in patients who were successfully treated with multi-drug therapy. These results suggest that M. leprae suppresses lipid degradation through inhibition of HSL expression, and that the monitoring of HSL mRNA levels in slit-skin smear specimens may be a useful indicator of patient prognosis.

Changes in white adipose tissue metabolism induced by resveratrol in rats

BackgroundA remarkable range of biological functions have been ascribed to resveratrol. Recently, this polyphenol has been shown to have body fat lowering effects. The aim of the present study was to assess some of the potential underlying mechanisms of action which take place in adipose tissue.MethodsSixteen male Sprague-Dawley rats were randomly divided into two groups: control and treated with 30 mg resveratrol/kg body weight/d. All rats were fed an obesogenic diet and after six weeks of treatment white adipose tissues were dissected. Lipoprotein lipase activity was assessed by fluorimetry, acetyl-CoA carboxylase by radiometry, and malic enzyme, glucose-6P-dehydrogenase and fatty acid synthase by spectrophotometry. Gene expression levels of acetyl-CoA carboxylase, fatty acid synthase, lipoprotein lipase, hormone-sensitive lipase, adipose triglyceride lipase, PPAR-gamma, SREBP-1c and perilipin were assessed by Real time RT-PCR. The amount of resveratrol metabolites in adipose tissue was measured by chromatography.ResultsThere was no difference in the final body weight of the rats; however, adipose tissues were significantly decreased in the resveratrol-treated group. Resveratrol reduced the activity of lipogenic enzymes, as well as that of heparin-releasable lipoprotein lipase. Moreover, a significant reduction was induced by this polyphenol in hormone-sensitive lipase mRNA levels. No significant changes were observed in other genes. Total amount of resveratrol metabolites in adipose tissue was 2.66 ± 0.55 nmol/g tissue.ConclusionsIt can be proposed that the body fat-lowering effect of resveratrol is mediated, at least in part, by a reduction in fatty acid uptake from circulating triacylglycerols and also in de novo lipogenesis.

Fasting and post-prandial adipose tissue lipoprotein lipase and hormone-sensitive lipase in obesity and Type 2 diabetes

Fasting and post-prandial abnormalities of adipose tissue (AT) lipoprotein lipase (LPL) and hormone- sensitive lipase (HSL) activities may have pathophysiological relevance in insulin-resistant conditions. The aim of this study was to evaluate activity and gene expression of AT LPL and HSL at fasting and 6 h after meal in two insulin-resistant groups - obese with Type 2 diabetes and obese without diabetes - and in non-diabetic normal-weight controls. Nine obese subjects with diabetes, 10 with obesity alone, and 9 controls underwent measurements of plasma levels of glucose, insulin, and triglycerides before and after a standard fat-rich meal. Fasting and post-prandial (6 h) LPL and HSL activities and gene expressions were determined in abdominal subcutaneous AT needle biopsies. The diabetic obese subjects had significantly lower fasting and post-prandial AT heparin-releasable LPL activity than only obese and control subjects (p<0.05) as well as lower mRNA LPL levels. HSL activity was significantly reduced in the 2 groups of obese subjects compared to controls in both fasting condition and 6 h after the meal (p<0.05), while HSL mRNA levels were not different. There were no significant changes between fasting and 6 h after meal measurements in either LPL or HSL activities and gene expressions. Lipolytic activities in AT are differently altered in obesity and Type 2 diabetes being HSL alteration associated with both insulin-resistant conditions and LPL with diabetes per se. These abnormalities are similarly observed in the fasting condition and after a fat-rich meal.

Effect of pu‐erh tea on body fat and lipid profiles in rats with diet‐induced obesity

The antiobesity and antihyperlipidaemic effects of pu-erh tea in rats with high fat diet (HFD)-induced obesity were investigated. Male Sprague-Dawley rats were randomly divided into five groups and fed varying diets for an 8-week period: control diet, HFD, and HFD supplemented with low, moderate or high doses of pu-erh tea extract (0.5 g, 2 g and 4 g/kg BW/day, respectively). Pu-erh tea significantly reduced the total body weight and the weight of various adipose pads. Pu-erh tea administration also significantly lowered plasma total cholesterol, triglyceride concentrations and low-density lipoprotein-cholesterol levels in rats with HFD-induced obesity, but did not affect high-density lipoprotein-cholesterol levels. Moreover, pu-erh tea significantly increased lipoprotein lipase, hepatic lipase and hormone-sensitive lipase activities in epididymal fat tissue in rats with HFD-induced obesity. Analysis of real-time reverse transcription-polymerase chain reaction results indicated that pu-erh tea significantly enhanced mRNA levels of hormone-sensitive lipase in rats with HFD-induced obesity. These results suggest that pu-erh tea attenuated visceral fat accumulation and improved hyperlipidemia in a rat model of HFD-induced obesity.

Combined Gene and Protein Expression of Hormone-Sensitive Lipase and Adipose Triglyceride Lipase, Mitochondrial Content, and Adipocyte Size in Subcutaneous and Visceral Adipose Tissue of Morbidly Obese Men

Aims: Lipotoxicity in obesity might be a failure of adipocytes to respond sufficiently adequate to persistent energy surplus. To evaluate the role of lipolytic enzymes or mitochondria in lipotoxicity, we studied expression levels of genes and proteins involved in lipolysis and mitochondrial DNA (mtDNA) content. Methods: As differences in lipid metabolism between men and women are extremely complex, we recruited only men (lean and morbidly obese) and collected subcutaneous and visceral adipose tissue during abdominal surgery for real-time PCR gene expression, protein expression, and microscopic study. Results: Although mRNA levels of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) were increased in visceral adipose tissue of morbidly obese men, this was not paralleled by alterations in protein expression and phosphorylation of HSL and ATGL. mtDNA content of visceral adipose tissue was increased in morbidly obese men as compared to lean controls (p < 0.013). Positive correlations were observed between visceral adipocyte size and serum triacylglycerol (r = 0.6, p < 0.007) as well as between visceral adipocyte size and CRP (r = 0.6, p < 0.009) in analyses performed separately in obese men. Conclusion: Lipotoxicity of morbidly obese men might be related to the quantitative impact of the visceral fat depot rather than to important dysregulation of involved lipolytic enzymes or adipocyte mitochondria.