scholarly journals Intra-Abdominal Fat Adipocyte Hypertrophy through a Progressive Alteration of Lipolysis and Lipogenesis in Metabolic Syndrome Rats

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1529 ◽  
Author(s):  
Israel Pérez-Torres ◽  
Yolanda Gutiérrez-Alvarez ◽  
Verónica Guarner-Lans ◽  
Eulises Díaz-Díaz ◽  
Linaloe Manzano Pech ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Feedback Loop ◽  
Abdominal Fat ◽  
Hormone Sensitive Lipase ◽  
Male Wistar Rats ◽  
Perilipin A ◽  
Hormone Sensitive ◽  
Adipocyte Hypertrophy ◽  
Advanced Glycosylation ◽  
Histological Staining

This study evaluates the progressive participation of enzymes involved in lipolysis and lipogenesis, leading to adipocyte hypertrophy in a metabolic syndrome (MS) rat model caused by chronic consumption of 30% sucrose in drinking water. A total of 70 male Wistar rats were divided into two groups: C and MS. Each of these groups were then subdivided into five groups which were sacrificed as paired groups every month from the beginning of the treatment until 5 months. The intra-abdominal fat was dissected, and the adipocytes were extracted. Lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), protein kinases A (PKA), and perilipin A expressions were determined. The LPL and HSL activities were evaluated by spectrophotometry. Histological staining was performed in adipose tissue. Significant increases were observed in blood pressure, HOMA-IR, leptin, triglycerides, insulin, intra-abdominal fat, and number of fat cells per field (p = 0.001) and in advanced glycosylation products, adipocyte area, LPL, HSL activities and/or expression (p ≤ 0.01) in the MS groups progressively from the third month onward. Lipogenesis and lipolysis were increased by LPL activity and HSL activity and/or expression. This was associated with hyperinsulinemia and release of non-esterified fatty acids causing a positive feedback loop that contributes to the development of adipocyte hypertrophy.

scholarly journals Perilipin A is essential for the translocation of hormone-sensitive lipase during lipolytic activation

2003 ◽  
Vol 161 (6) ◽  
pp. 1093-1103 ◽  
Author(s):  
Carole Sztalryd ◽  
Guoheng Xu ◽  
Heidi Dorward ◽  
John T. Tansey ◽  
Juan A. Contreras ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Chinese Hamster Ovary ◽  
Lipid Droplets ◽  
Chinese Hamster ◽  
Hormone Sensitive Lipase ◽  
Ovary Cell ◽  
Perilipin A ◽  
Hormone Sensitive ◽  
Kinase A

Akey step in lipolytic activation of adipocytes is the translocation of hormone-sensitive lipase (HSL) from the cytosol to the surface of the lipid storage droplet. Adipocytes from perilipin-null animals have an elevated basal rate of lipolysis compared with adipocytes from wild-type mice, but fail to respond maximally to lipolytic stimuli. This defect is downstream of the β-adrenergic receptor–adenylyl cyclase complex. Now, we show that HSL is basally associated with lipid droplet surfaces at a low level in perilipin nulls, but that stimulated translocation from the cytosol to lipid droplets is absent in adipocytes derived from embryonic fibroblasts of perilipin-null mice. We have also reconstructed the HSL translocation reaction in the nonadipocyte Chinese hamster ovary cell line by introduction of GFP-tagged HSL with and without perilipin A. On activation of protein kinase A, HSL-GFP translocates to lipid droplets only in cells that express fully phosphorylatable perilipin A, confirming that perilipin is required to elicit the HSL translocation reaction. Moreover, in Chinese hamster ovary cells that express both HSL and perilipin A, these two proteins cooperate to produce a more rapidly accelerated lipolysis than do cells that express either of these proteins alone, indicating that lipolysis is a concerted reaction mediated by both protein kinase A–phosphorylated HSL and perilipin A.

scholarly journals Evidence of a possible role for Lys-γ3-MSH in the regulation of adipocyte function

2007 ◽  
Vol 196 (1) ◽  
pp. 149-158 ◽  
Author(s):  
Stephen C Harmer ◽  
David J Pepper ◽  
Katy Cooke ◽  
Hugh P J Bennett ◽  
Andrew B Bicknell
Keyword(s):  
Physiological Role ◽  
Hormone Sensitive Lipase ◽  
Melanocortin Receptor ◽  
Rat Tissues ◽  
Binding Studies ◽  
Cortical Cells ◽  
Perilipin A ◽  
Hormone Sensitive ◽  
Adrenal Cortical Cells

Lys-γ3-MSH is a melanocortin peptide derived from the C-terminal of the 16 kDa fragment of POMC. The physiological role of Lys-γ3-MSH is unclear, although it has previously been shown that, although not directly steroidogenic, it can act to potentiate the steroidogenic response of adrenal cortical cells to ACTH. This synergistic effect appears to be correlated with an ability to increase the activity of hormone sensitive lipase (HSL) and therefore the rate of cholesterol ester hydrolysis. Ligand binding studies have suggested that high-affinity binding sites for Lys-γ3-MSH exist in the adrenal gland and a number of other rat tissues that express HSL, including adipose, skeletal muscle and testes. To investigate the hypothesis that Lys-γ3-MSH may play a wider role in cholesterol and lipid metabolism, we tested the effect of Lys-γ3-MSH on lipolysis, an HSL-mediated process, in 3T3-L1 adipocytes. In comparison with other melanocortin peptides, Lys-γ3-MSH was found to be a potent stimulator of lipolysis. It was also able to phosphorylate HSL at key serine residues and stimulate the hyperphosphorylation of perilipin A. The receptor through which the lipolytic actions of Lys-γ3-MSH are being mediated is not clear. Attempts to characterise this receptor suggest that either the pharmacology of the melanocortin receptor 5 in 3T3-L1 adipocytes is different from that described when expressed in heterologous systems or the possibility that a further, as yet uncharacterised, receptor exists.

scholarly journals Central melanocortin stimulation increases phosphorylated perilipin A and hormone-sensitive lipase in adipose tissues

2010 ◽  
Vol 299 (1) ◽  
pp. R140-R149 ◽  
Author(s):  
Y. B. Shrestha ◽  
C. H. Vaughan ◽  
B. J. Smith ◽  
C. K. Song ◽  
D. J. Baro ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Sympathetic Nerves ◽  
Hormone Sensitive Lipase ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Perilipin A ◽  
Hormone Sensitive

Norepinephrine (NE) released from the sympathetic nerves innervating white adipose tissue (WAT) is the principal initiator of lipolysis in mammals. Central WAT sympathetic outflow neurons express melanocortin 4-receptor (MC4-R) mRNA. Single central injection of melanotan II (MTII; MC3/4-R agonist) nonuniformly increases WAT NE turnover (NETO), increases interscapular brown adipose tissue (IBAT) NETO, and increases the circulating lipolytic products glycerol and free fatty acid. The WAT pads that contributed to this lipolysis were inferred from the increases in NETO. Because phosphorylation of perilipin A (p-perilipin A) and hormone-sensitive lipase are necessary for NE-triggered lipolysis, we tested whether MTII would increase these intracellular markers of lipolysis. Male Siberian hamsters received a single 3rd ventricular injection of MTII or saline. Trunk blood was collected at 0.5, 1.0, and 2.0 h postinjection from excised inguinal, retroperitoneal, and epididymal WAT (IWAT, RWAT, and EWAT, respectively) and IBAT pads. MTII increased circulating glycerol concentrations at 0.5 and 1.0 h, whereas free fatty acid concentrations were increased at 1.0 and 2.0 h. Western blot analysis showed that MTII specifically increased p-perilipin A and hormone-sensitive lipase only in fat pads that previously had MTII-induced increases in NETO. Phosphorylation increased in IWAT at all time points and IBAT at 0.5 h, but not RWAT or EWAT at any time point. These results show for the first time in rodents that p-perilipin A can serve as an in vivo, fat pad-specific indictor of lipolysis and extend our previous findings showing that central melanocortin stimulation increases WAT lipolysis.

scholarly journals Heterogeneity in the physiological states and pharmacological responses of differentiating 3T3-L1 preadipocytes

2009 ◽  
Vol 187 (3) ◽  
pp. 375-384 ◽  
Author(s):  
Lit-Hsin Loo ◽  
Hai-Jui Lin ◽  
Dinesh K. Singh ◽  
Kathleen M. Lyons ◽  
Steven J. Altschuler ◽  
...  
Keyword(s):  
Immunofluorescence Microscopy ◽  
Hormone Sensitive Lipase ◽  
Molecular Heterogeneity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Specific Effects ◽  
Enhancer Binding Protein ◽  
Perilipin A ◽  
Pparγ Agonists ◽  
Hormone Sensitive

Increases in key components of adipogenesis and lipolysis pathways correlate at the population-averaged level during adipogenesis. However, differentiating preadipocytes are highly heterogeneous in cellular and lipid droplet (LD) morphologies, and the degree to which individual cells follow population-averaged trends is unclear. In this study, we analyze the molecular heterogeneity of differentiating 3T3-L1 preadipocytes using immunofluorescence microscopy. Unexpectedly, we only observe a small percentage of cells with high simultaneous expression of markers for adipogenesis (peroxisome proliferator-activated receptor γ [PPARγ], CCAAT/enhancer-binding protein α, and adiponectin) and lipid accumulation (hormone-sensitive lipase, perilipin A, and LDs). Instead, we identify subpopulations of cells with negatively correlated expressions of these readouts. Acute perturbation of adipocyte differentiation with PPARγ agonists, forskolin, and fatty acids induced subpopulation-specific effects, including redistribution of the percentage of cells in observed subpopulations and differential expression levels of PPARγ. Collectively, our results suggested that heterogeneity observed during 3T3-L1 adipogenesis reflects a dynamic mixture of subpopulations with distinct physiological states.

scholarly journals Alisol A 24-acetate stimulates lipolysis in 3 T3-L1 adipocytes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hai-xia Lou ◽  
Wen-cheng Fu ◽  
Jia-xiang Chen ◽  
Tian-tian Li ◽  
Ying-ying Jiang ◽  
...  
Keyword(s):  
Biological Activities ◽  
Quantitative Polymerase Chain Reaction ◽  
Underlying Mechanism ◽  
Hormone Sensitive Lipase ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Alisma Orientale ◽  
Perilipin A ◽  
Hormone Sensitive

Abstract Background Alisol A 24-acetate (AA-24-a), one of the main active triterpenes isolated from the well-known medicinal plant Alisma orientale (Sam.) Juz., exhibits multiple biological activities including hypolipidemic activity. However, its effect on lipid metabolism in adipocytes remains unclear. The present study aimed to clarify the effect of AA-24-a on adipocyte lipolysis and to determine its potential mechanism of action using 3 T3-L1 cells. Methods We assayed the release of glycerol into culture medium of 3 T3-L1 cells under treatment with AA-24-a. Protein and mRNA expression and phosphorylation levels of the main lipases and kinases involved in lipolysis regulation were determined by quantitative polymerase chain reaction and western blotting. Specific inhibitors of protein kinase A (PKA; H89) and extracellular signal-regulated kinase (ERK; PD98059), which are key enzymes in relevant signaling pathways, were used to examine their roles in AA-24-a-stimulated lipolysis. Results AA-24-a significantly stimulated neutral lipolysis in fully differentiated adipocytes. To determine the underlying mechanism, we assessed the changes in mRNA and protein levels of key lipolysis-related genes in the presence or absence of H89 and PD98059. Both inhibitors reduced AA-24-a-induced lipolysis. Moreover, pretreatment with H89 attenuated AA-24-a-induced phosphorylation of hormone-sensitive lipase at Ser660, while pretreatment with PD98059 attenuated AA-24-a-induced downregulation of peroxisome proliferator-activated receptor-γ and perilipin A. Conclusions Our results indicate that AA-24-a promoted neutral lipolysis in 3 T3-L1 adipocytes by activating PKA-mediated phosphorylation of hormone-sensitive lipase and ERK- mediated downregulation of expression of perilipin A.

scholarly journals Modulation of Hormone-sensitive Lipase and Protein Kinase A-mediated Lipolysis by Perilipin A in an Adenoviral Reconstituted System

2001 ◽  
Vol 277 (10) ◽  
pp. 8267-8272 ◽  
Author(s):  
Sandra C. Souza ◽  
Kizito V. Muliro ◽  
Laura Liscum ◽  
Ping Lien ◽  
Mia T. Yamamoto ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Hormone Sensitive Lipase ◽  
Perilipin A ◽  
Hormone Sensitive ◽  
Reconstituted System ◽  
Kinase A

scholarly journals Effect of diet on fat cell size and hormone-sensitive lipase activity

1999 ◽  
Vol 87 (1) ◽  
pp. 227-232 ◽  
Author(s):  
Joshua J. Berger ◽  
R. James Barnard
Keyword(s):  
Insulin Resistance ◽  
Plasma Free Fatty Acid ◽  
Hormone Sensitive Lipase ◽  
Fischer 344 Rats ◽  
High Fat ◽  
Fat Cell ◽  
Fischer 344 ◽  
Hormone Sensitive ◽  
Adipocyte Hypertrophy ◽  
The Relationship

This study was designed to examine the relationship between diet-induced insulin resistance/hyperinsulinemia, fat cell hypertrophy, and hormone-sensitive lipase (HSL) to elucidate whether an attenuated HSL activity leads to obesity. Female Fischer 344 rats were fed either a low-fat, complex-carbohydrate diet or a high-fat, refined-sugar (HFS) diet for 2 wk, 2 mo, or 6 mo. Adipose tissue morphology and HSL activity as well as plasma free fatty acid and glycerol levels were determined at these times. No differences between groups were seen after 2 wk except the previously reported hyperinsulinemia in the HFS animals. At both 2 and 6 mo, the HFS animals demonstrated adipocyte hypertrophy. Basal and stimulated HSL activities and plasma glycerol were significantly elevated in the HFS group. There was a positive correlation between adipocyte size and HSL activity for both basal and stimulated states. These results demonstrate that an attenuated HSL activity is not observed with the onset of insulin resistance/hyperinsulinemia and therefore does not play a role in the development of obesity.

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