scholarly journals Hormone-sensitive lipase deficiency alters gene expression and cholesterol content of mouse testis

Reproduction ◽  
2017 ◽  
Vol 153 (2) ◽  
pp. 175-185 ◽  
Author(s):  
Feng Wang ◽  
Zheng Chen ◽  
Xiaofang Ren ◽  
Ye Tian ◽  
Fucheng Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Cholesterol Content ◽  
Hormone Sensitive Lipase ◽  
Protein Distribution ◽  
Wild Type ◽  
Cholesterol Levels ◽  
Hormone Sensitive ◽  
Elongation Phase

Hormone-sensitive lipase-knockout (HSL−/−) mice exhibit azoospermia for unclear reasons. To explore the basis of sterility, we performed the following three experiments. First, HSL protein distribution in the testis was determined. Next, transcriptome analyses were performed on the testes of three experimental groups. Finally, the fatty acid and cholesterol levels in the testes with three different genotypes studied were determined. We found that the HSL protein was present from spermatocyte cells to mature sperm acrosomes in wild-type (HSL+/+) testes. Spermiogenesis ceased at the elongation phase of HSL−/− testes. Transcriptome analysis indicated that genes involved in lipid metabolism, cell membrane, reproduction and inflammation-related processes were disordered in HSL−/− testes. The cholesterol content was significantly higher in HSL−/− than that in HSL+/+ testis. Therefore, gene expression and cholesterol ester content differed in HSL−/− testes compared to other testes, which may explain the sterility of male HSL−/− mice.

scholarly journals Metabolic characteristics of a human hepatoma cell line stably transfected with hormone-sensitive lipase

1999 ◽  
Vol 341 (2) ◽  
pp. 453-460 ◽  
Author(s):  
Richard J. PEASE ◽  
David WIGGINS ◽  
E. David SAGGERSON ◽  
Jeni TREE ◽  
Geoffrey F. GIBBONS
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Hepatoma Cell ◽  
Hormone Sensitive Lipase ◽  
Acid Oxidation ◽  
Hepatoma Cell Line ◽  
Wild Type ◽  
Transfected Cells ◽  
Oxidative Pathway ◽  
Hormone Sensitive

Clones of HepG2 cells were selected that stably express the cDNA for hormone-sensitive lipase (HSL). When cells were cultured in the presence of labelled extracellular oleate, accumulation of labelled fatty acid as cellular triacylglycerol (TAG) was significantly lower in the transfectants compared with the wild-type cells. There was no change in the net rate of phospholipid (PL) synthesis. Culture of cells containing isotopically prelabelled TAG resulted in a greater net loss of TAG from the transfected cells than from the wild-type cells. The excess loss of labelled TAG was primarily due to an increased TAG fatty acid oxidation. Free fatty acid release into the medium was not increased in the transfectants, nor was the very low rate of lipoprotein lipid secretion. Also, there was no increased net trafficking of fatty acids from TAG into PLs. Changes in the 3H:14C ratio of TAG prelabelled with [3H]glycerol and [14C]oleate suggested that none of excess TAG fatty acid released in the transfected cells underwent intracellular re-esterification to TAG prior to oxidation. The results suggest that fatty acids mobilized by HSL are directed immediately into the oxidative pathway and are not available for biosynthetic processes. It appears likely, therefore, that intracellular TAG-derived fatty acids which enter the oxidative pathway exist in a different compartment from those that are directed towards synthesis.

Zinc-α2-Glycoprotein Knockout Influenced Genes Expression Profile in Adipose Tissue and Decreased the Lipid Mobilizing After Dexamethasone Treatment in Mice

2020 ◽  
Vol 52 (10) ◽  
pp. 755-763
Author(s):  
Wenge Zhang ◽  
Yu Qiao ◽  
Fulei Qi ◽  
Qingyi Shen ◽  
Ruqian Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Visceral Fat ◽  
Fatty Acid Synthase ◽  
Wild Type ◽  
Genes Expression

AbstractZinc-α2-glycoprotein (ZAG), as an adipokine, plays an important role in lipid metabolism. However, its influence on whole gene expression profile in adipose tissue is not known. Under stress condition, how ZAG affects the lipid metabolism is also unclear. Therefore, in this study ZAG systemic knockout (KO) mice were used as a model to reveal the genes expression profile in visceral fat tissues of ZAG KO mice and wild-type mice by genome-wide microarray screening. Then dexamethasone (DEX) was used to explore the effect of ZAG deletion on body fat metabolism under stress. Our results showed that 179 genes were differentially expressed more than 1.5 times between ZAG KO mice and wild type mice, of which 26 genes were upregulated dramatically and 153 genes were significantly downregulated. Under DEX simulated stress, ZAG systemic knockout in vivo resulted in a markedly decrease of triglycerides (TG) and nonesterified fatty acid (NEFA) content in in plasma. Similarly, for lipid catabolism, ZAG KO led to a significant increase of phosphorylated HSL (p-HSL) protein and a rising tendency of adipose triglyceride lipase (ATGL) protein relative to those of the DEX group. For lipid anabolism, fatty acid synthase (FAS) and adiponectin protein expression in visceral fat rose notably in ZAG KO mice after DEX treatment. In conclusion, ZAG knockout can affect the gene expression profile of adipose tissue, reduce elevated TG and NEFA levels in plasma, and alter lipid metabolism under DEX treatment. These findings provide new insights into the mechanism of lipid metabolic disorders in response to stress.

scholarly journals Cellular retinol-binding protein type III is a PPARγ target gene and plays a role in lipid metabolism

2008 ◽  
Vol 295 (6) ◽  
pp. E1358-E1368 ◽  
Author(s):  
Cynthia F. Zizola ◽  
Gary J. Schwartz ◽  
Silke Vogel
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Free Fatty Acid ◽  
Target Gene ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Wild Type ◽  
Type Iii ◽  
Cellular Retinol Binding Protein

Cellular retinol-binding protein (CRBP) type III (CRBP-III) belongs to the family of intracellular lipid-binding proteins, which includes the adipocyte-binding protein aP2. In the cytosol, CRBP-III binds retinol, the precursor of retinyl ester and the active metabolite retinoic acid. The goal of the present work is to understand the regulation of CRBP-III expression and its role in lipid metabolism. Using EMSAs, luciferase reporter assays, and chromatin immunoprecipitation assays, we found that CRBP-III is a direct target of peroxisome proliferator-activated receptor-γ (PPARγ). Moreover, CRBP-III expression was induced in adipose tissue of mice after treatment with the PPARγ agonist rosiglitazone. To examine a potential role of CRBP-III in regulating lipid metabolism in vivo, CRBP-III-deficient (C-III-KO) mice were maintained on a high-fat diet (HFD). Hepatic steatosis was decreased in HFD-fed C-III-KO compared with HFD-fed wild-type mice. These differences were partly explained by decreased serum free fatty acid levels and decreased free fatty acid efflux from adipose tissue of C-III-KO mice. In addition, the lack of CRBP-III was associated with reduced food intake, increased respiratory energy ratio, and altered body composition, with decreased adiposity and increased lean body mass. Furthermore, expression of genes involved in mitochondrial fatty acid oxidation in brown adipose tissue was increased in C-III-KO mice, and C-III-KO mice were more cold tolerant than wild-type mice fed an HFD. In summary, we demonstrate that CRBP-III is a PPARγ target gene and plays a role in lipid and whole body energy metabolism.

Fatty acid oxidation and triacylglycerol hydrolysis are enhanced after chronic leptin treatment in rats

2002 ◽  
Vol 282 (3) ◽  
pp. E593-E600 ◽  
Author(s):  
Gregory R. Steinberg ◽  
Arend Bonen ◽  
David J. Dyck
Keyword(s):  
Fatty Acid ◽  
Citrate Synthase ◽  
Uncoupling Protein ◽  
Oxidative Capacity ◽  
Hormone Sensitive Lipase ◽  
Acid Oxidation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Triacylglycerol Hydrolysis ◽  
Hormone Sensitive

Leptin acutely increases fatty acid (FA) oxidation and triacylglycerol (TG) hydrolysis and decreases TG esterification in oxidative rodent muscle. However, the effects of chronic leptin administration on FA metabolism in skeletal muscle have not been examined. We hypothesized that chronic leptin treatment would enhance TG hydrolysis as well as the capacity to oxidize FA in soleus (SOL) muscle. Female Sprague-Dawley rats were infused for 2 wk with leptin (LEPT; 0.5 mg · kg−1 · day−1) by use of subcutaneously implanted miniosmotic pumps. Control (AD-S) and pair-fed (PF-S) animals received saline-filled implants. Subsequently, FA metabolism was monitored for 45 min in isolated, resting, and contracting (20 tetani/min) SOL muscles by means of pulse-chase procedures. Food intake (−33 ± 2%, P < 0.01) and body mass (−12.5 ± 4%, P = 0.01) were reduced in both LEPT and PF-S animals. Leptin levels were elevated (+418 ± 7%, P < 0.001) in treated animals but reduced in PF-S animals (−73 ± 8%, P< 0.05) relative to controls. At rest, TG hydrolysis was increased in leptin-treated rats (1.8 ± 2.2, AD-S vs. 23.5 ± 8.1 nmol/g wet wt, LEPT; P < 0.001). In contracting SOL muscles, TG hydrolysis (1.5 ± 0.6, AD-S vs. 3.6 ± 1.0 μmol/g wet wt, LEPT; P = 0.02) and palmitate oxidation (18.3 ± 6.7, AD-S vs. 45.7 ± 9.9 nmol/g wet wt, LEPT; P < 0.05) were both significantly increased by leptin treatment. Chronic leptin treatment had no effect on TG esterification either at rest or during contraction. Markers of overall (citrate synthase) and FA (hydroxyacyl-CoA dehydrogenase) oxidative capacity were unchanged with leptin treatment. Protein expression of hormone-sensitive lipase (HSL) was also unaltered following leptin treatment. Thus leptin-induced increases in lipolysis are likely due to HSL activation (i.e., phosphorylation). Increased FA oxidation secondary to chronic leptin treatment is not due to an enhanced oxidative capacity and may be a result of enhanced flux into the mitochondrion (i.e., carnitine palmitoyltransferase I regulation) or electron transport uncoupling (i.e., uncoupling protein-3 expression).

scholarly journals Miltefosine Affects Lipid Metabolism in Leishmania donovani Promastigotes

2007 ◽  
Vol 51 (4) ◽  
pp. 1425-1430 ◽  
Author(s):  
M. Rakotomanga ◽  
S. Blanc ◽  
K. Gaudin ◽  
P. Chaminade ◽  
P. M. Loiseau
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Leishmania Donovani ◽  
Cholesterol Content ◽  
Strong Reduction ◽  
Drug Pressure ◽  
Antileishmanial Drug ◽  
Partial Inactivation ◽  
Orally Active

ABSTRACT Miltefosine (hexadecylphosphocholine [HePC]) is the first orally active antileishmanial drug. Transient HePC treatment of Leishmania donovani promastigotes at 10 μM significantly reduced the phosphatidylcholine content and enhanced the phosphatidylethanolamine (PE) content in parasite membranes, suggesting a partial inactivation of PE-N-methyltransferase. Phospholipase D activity did not seem to be affected by HePC. In addition, the enhancement of the lysophosphatidylcholine content could be ascribed to phospholipase A2 activation. Moreover, transient HePC treatment had no effect on the fatty acid alkyl chain length or the fatty acid unsaturation rate. Concerning sterols, we found a strong reduction of the C24 alkylated sterol content, and the enhancement of the cholesterol content could be the result of the HePC condensation effect with sterols. Because some of the effects observed after transient HePC treatment were different from those previously observed in HePC-resistant parasites, it could be hypothesized that continuous in vitro drug pressure induces the mechanisms of regulation in Leishmania lipid metabolism.

scholarly journals Physical Association between the Adipocyte Fatty Acid-binding Protein and Hormone-sensitive Lipase

2004 ◽  
Vol 279 (50) ◽  
pp. 52399-52405 ◽  
Author(s):  
Anne J. Smith ◽  
Mark A. Sanders ◽  
Brian R. Thompson ◽  
Constantine Londos ◽  
Fredric B. Kraemer ◽  
...  
Keyword(s):  
Energy Transfer ◽  
Fatty Acid ◽  
Fluorescence Resonance Energy Transfer ◽  
Fluorescent Protein ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Hormone Sensitive Lipase ◽  
Fatty Acid Binding ◽  
Hormone Sensitive ◽  
Fluorescence Resonance

Previousin vitrostudies have established that hormone sensitive lipase (HSL) and adipocyte fatty acid-binding protein (AFABP) form a physical complex that presumably positions the FABP to accept a product fatty acid generated during catalysis. To assess AFABP-HSL interaction within a cellular context, we have used lipocytes derived from 293 cells (C8PA cells) and examined physical association using fluorescence resonance energy transfer. Transfection of C8PA cells with cyan fluorescent protein (CFP)-HSL, yellow fluorescent protein (YFP)-adipocyte FABP, or YFP-liver FABP revealed that under basal conditions each protein was cytoplasmic. In the presence of 20 μmforskolin, CFP-HSL translocated to the triacylglycerol droplet, coincident with BODIPY-FA labeled depots. Fluorescence resonance energy transfer analysis demonstrated that CFP-HSL associated with YFP-adipocyte FABP in both basal and forskolin-treated cells. In contrast, little if any fluorescence resonance energy transfer could be detected between CFP-HSL and YFP-liver FABP. These results suggest that a pre-lipolysis complex containing at least AFABP and HSL exists and that the complex translocates to the surface of the lipid droplet.

scholarly journals Effects of dietary n -6: n -3 PUFA ratio on the growth performance, serum lipid and adipokine profiles, tissue fatty acid composition and gene expression of lipid metabolism of finishing pigs

2020 ◽  
Author(s):  
Jing Chen ◽  
Jiantao Li ◽  
Xianjun Liu ◽  
Hongze Cui ◽  
Liyan Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Growth Performance ◽  
Acid Composition ◽  
Blood Lipid ◽  
Finishing Pigs ◽  
Pufa Ratio ◽  
Tissue Fatty Acid Composition

Abstract Background The health benefits of n-3 polyunsaturated fatty acids (PUFA), such as cardioprotective, anti-inflammatory and hypo-triglyceridemic properties, have been well documented. However, current dietary modification can easily lead to excessive concentrations of n-6 PUFA and an imbalance in the n-6:n-3 PUFA ratio, resulting in the pathogenesis of obesity and related diseases. This study investigated the effects of various dietary n-6:n-3 PUFA ratios on the growth performance, blood lipid and cytokine profiles, tissue fatty acid composition, and gene expression involved in lipid metabolism in finishing pigs. Seventy-two crossbred [(Duroc × Landrace) × Yorkshire] finishing pigs (68.5 ± 1·8 kg) were fed one of four isoenergetic diets with n-6:n-3 PUFA ratios of 2:1, 3:1, 5:1 and 8:1. Results Pigs fed diets with n-6:n-3 PUFA ratios of 3:1 and 5:1 had a higher average daily gain (ADG) and average daily feed intake (ADFI) (P < 0.05) and a lower feed conversion ratio (FCR) (P < 0.05). The concentrations of triglyceride (TG) and total cholesterol (TC) of pigs fed diets with n-6:n-3 PUFA ratios of 1:1 to 5:1 decreased (P < 0·05), whereas the ratio of concentrations of high-density to low-density lipoprotein cholesterol (HDL-C:LDL-C) in pigs fed a diet with an n-6:n-3 PUFA ratio of 2:1 increased (P < 0·05) compared with those fed a diet with an n-6:n-3 PUFA ratio of 8:1. Pigs fed a diet with n-6:n-3 PUFA ratios of 2:1 and 3:1 had lower concentrations of leptin (LEP) and interleukin 6 (IL-6) (P < 0·05), and higher concentrations of adiponectin (APN) (P < 0·05) than those fed diets with n-6:n-3 PUFA ratios of 5:1 and 8:1. Diets with n-6:n-3 PUFA ratios of 2:1 and 3:1 markedly down-regulated the expression levels of peroxisome proliferator-activated receptor-γ (PPARγ) and lipoprotein lipase (LPL) in both the longissimus dorsi muscle (LM) and subcutaneous adipose tissue (SCAT), but up-regulated the expression level of adipocyte fatty acid binding protein (aP2) in the LM. The expression levels of aP2 and hormone- sensitive lipase were similar to those of PPARγ in the SCAT. Conclusions This study demonstrated that dietary n-6:n-3 PUFA ratios between 3:1 and 5:1 beneficially affected growth performance, optimize blood lipid and adipocytokine levels, enhanced absorption and deposition of n-3 PUFA and regulated lipid metabolism-related genes.

scholarly journals PO-193 Exercise training decreased lipid accumulation in murine skeletal muscle through Sestrin2-mediated SHIP2-JNK signaling pathway

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Tianyi Wang ◽  
Song Huang ◽  
Xiao Han ◽  
Sujuan Liu ◽  
Yanmei Niu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Exercise Training ◽  
High Fat Diet ◽  
De Novo ◽  
Underlying Mechanism ◽  
Wild Type ◽  
High Fat

Objective Obesity is becoming increasingly prevalent and is an important contributor to the worldwide burden of diseases. It is widely accepted that exercise training is beneficial for the prevention and treatment of obesity. However, the underlying mechanism by which exercise training improving skeletal muscle lipid metabolism is still not fully described. Sestrins (Sestrin1-3) are highly conserved stress-inducible protein. Concomitant ablation of Sestrin2 and Sestrin3 has been reported to provoke hepatic mTORC1/S6K1 activation and insulin resistance even without nutritional overload and obesity, implicating that Sestrin2 and Sestrin3 have an important homeostatic function in the control of mammalian glucose and lipid metabolism. Our previous results demonstrated that physical exercise increased Sestrin2 expression in murine skeletal muscle, while the role of Sestrin2 in regulating lipid metabolism remains unknown.  SH2 domain containing inositol 5-phosphatase (SHIP2) acts as a negative regulator of the insulin signaling both in vitro and in vivo. An increased expression of SHIP2 inhibits the insulin-induced Akt activation, glucose uptake, and glycogen synthesis in 3T3-L1 adipocytes, L6 myotubes and tissues of animal models. Alterations of SHIP2 expression and/or enzymatic function appear to have a profound impact on the development of insulin resistance. However, the regulatory function of SHIP2 in lipid metabolism after exercise remains unclear. It has been reported that SHIP2 modulated lipid metabolism through regulating the activity of c-Jun N-terminal kinase (JNK) and Sterol regulatory element-binding protein-1 (SREBP-1). JNK is a subclass of mitogen-activated protein kinase (MAPK) signaling pathway in mammalian cells and plays a crucial role in metabolic changes and inflammation associated with a high-fat diet. Inhibition of JNK reduces lipid deposition and proteins level of fatty acid de novo synthesis in liver cells. It has been reported that Sestrin2 regulated the phosphorylation of JNK, however the underlying mechanism remains unclear. SREBP-1 is important in regulating cholesterol biosynthesis and uptake and fatty acid biosynthesis, and SREBP-1 expression produces two different isoforms, SREBP-1a and SREBP-1c. SREBP-1c is responsible for regulating the genes required for de novo lipogenesis and its expression is regulated by insulin. SREBP-1a regulates genes related to lipid and cholesterol production and its activity is regulated by sterol levels in the cell. Altogether, the purpose of this study was to explore the effect and underlying mechanism of Sestrin2 on lipid accumulation after exercise training. Methods Male wild type and SESN2−/− mice were divided into normal chow (NC) and high-fat diet (HFD) groups to create insulin resistance mice model. After 8 weeks the IR model group was then divided into HFD sedentary control and HFD exercise groups (HE). Mice in HE group underwent 6-week treadmill exercise to reveal the effect of exercise training on lipid metabolism in insulin resistance model induced by HFD. We explored the mechanism through which Sestrin2 regulated lipid metabolism in vitro by supplying palmitate, overexpressing or inhibiting SESNs, SHIP2 and JNK in myotubes. Results We found that 6-week exercise training decreased body weight, BMI and fat mass in wild type and SESN2-/- mice after high-fat diet (HFD) feeding. And exercise training decreased the level of plasma glucose, serum insulin, triglycerides and free fatty acids in wild type but not in Sestrin2-/- mice. Lipid droplet in skeletal muscle was also decreased in wild type but did not in Sestrin2-/- mice. Moreover, exercise training increased the proteins expression involved in fatty acid oxidation and decreased the proteins which related to fatty acid de novo synthesis. The results of oil red staining and the change of proteins related to fatty acid de novo synthesis and beta oxidation in myotubes treated with palmitate, Ad-SESN2 and siRNA-Sestrin2 were consisted with the results in vivo, which suggested that Sestrin2 was a key regulator in lipid metabolism. Exercise training increased Sestrin2 expression and reversed up-regulation of SHIP2 and pJNK induced by HFD in wild type mice but not in Sestrin2-/- mice. In parallel, overexpression of Sestrin2 decreased the level of SHIP2 and pJNK induced by palmitate while Sestrin2 knock down by siRNA-Sestrin2 treatment did not change the expression of SHIP2 and pJNK, which suggested that Sestrin2 modulated SHIP2 and JNK in the state of abnormal lipid metabolism. Inhibition of SHIP2 reduced the activity of JNK, increased lipid accumulation and the proteins of fatty acid synthesis after palmitate treatment and over expression of Sestrin2, which suggest that Sestrin2 modulated lipid metabolism through SHIP2/JNK pathway. Conclusions Sestrin2 plays an important role in improving lipid metabolism after exercise training, and Sestrin2 regulates lipid metabolism by SHIP2-JNK pathway in skeletal muscle.

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