scholarly journals Regulation of angiopoietin-like protein 4/fasting-induced adipose factor (Angptl4/FIAF) expression in mouse white adipose tissue and 3T3-L1 adipocytes

2008 ◽  
Vol 100 (1) ◽  
pp. 18-26 ◽  
Author(s):  
Sarah Dutton ◽  
Paul Trayhurn
Keyword(s):  
Skeletal Muscle ◽  
Cell Culture ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Culture Medium ◽  
Mrna Level ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Before And After ◽  
Stimulation Of

Angiopoietin-like protein 4 (Angptl4)/FIAF (fasting-induced adipose factor) was first identified as a target for PPAR and to be strongly induced in white adipose tissue (WAT) by fasting. Here we have examined the regulation of the expression and release of this adipokine in mouse WAT and in 3T3-L1 adipocytes. Angptl4/FIAF expression was measured by RT-PCR and real-time PCR; plasma Angptl4/FIAF and release of the protein in cell culture was determined by western blotting. The Angptl4/FIAF gene was expressed in each of the major WAT depots of mice, the mRNA level in WAT being similar to the liver and much higher (>50-fold) than skeletal muscle. Fasting mice (18 h) resulted in a substantial increase in Angptl4/FIAF mRNA in liver and muscle (9·5- and 21-fold, respectively); however, there was no effect of fasting on Angptl4/FIAF mRNA in WAT and the plasma level of Angptl4/FIAF was unchanged. The Angptl4/FIAF gene was expressed in 3T3-L1 adipocytes before and after differentiation, the level increasing post-differentiation; Angptl4/FIAF was released into the culture medium. Insulin, leptin, dexamethasone, noradrenaline, TNFα and several IL (IL-1β, IL-6, IL-10, IL-18) had little effect on Angptl4/FIAF mRNA levels in 3T3-L1 adipocytes. However, a major stimulation of Angptl4/FIAF expression was observed with rosiglitazone and the inflammatory prostaglandins PGD2 and PGJ2. Angptl4/FIAF does not act as an adipose tissue signal of nutritional status, but is markedly induced by fasting in liver and skeletal muscle.

NGF gene expression and secretion in white adipose tissue: regulation in 3T3-L1 adipocytes by hormones and inflammatory cytokines

2004 ◽  
Vol 287 (2) ◽  
pp. E331-E339 ◽  
Author(s):  
Muhammad R. Peeraully ◽  
John R. Jenkins ◽  
Paul Trayhurn
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Sympathetic Neurons ◽  
Mrna Levels ◽  
Rt Pcr ◽  
White Adipocytes ◽  
Pparγ Agonist ◽  
Tnf Α ◽  
Ngf Gene

The sympathetic nervous system plays a central role in lipolysis and the production of leptin in white adipose tissue (WAT). In this study, we have examined whether nerve growth factor (NGF), a target-derived neurotropin that is a key signal in the development and survival of sympathetic neurons, is expressed and secreted by white adipocytes. NGF mRNA was detected by RT-PCR in the major WAT depots of mice (epididymal, perirenal, omental, mesenteric, subcutaneous) and in human fat (subcutaneous, omental). In mouse WAT, NGF expression was observed in mature adipocytes and in stromal vascular cells. NGF expression was also evident in 3T3-L1 cells before and after differentiation into adipocytes. NGF protein, measured by ELISA, was secreted from 3T3-L1 cells, release being higher before differentiation. Addition of the sympathetic agonists norepinephrine, isoprenaline, or BRL-37344 (β3-agonist) led to falls in NGF gene expression and secretion by 3T3-L1 adipocytes, as did IL-6 and the PPARγ agonist rosiglitazone. A substantial decrease in NGF expression and secretion occurred with dexamethasone. In contrast, LPS increased NGF mRNA levels and NGF secretion. A major increase in NGF mRNA level (9-fold) and NGF secretion (≤40-fold) in 3T3-L1 adipocytes occurred with TNF-α. RT-PCR showed that the genes encoding the p75 and trkA NGF receptors were expressed in mouse WAT. These results demonstrate that white adipocytes secrete NGF (an adipokine), NGF synthesis being influenced by several factors with TNF-α having a major stimulatory effect. We suggest that NGF is a target-derived neurotropin and an inflammatory response protein in white adipocytes.

scholarly journals Effect of diabetes and fasting on GLUT-4 (muscle/fat) glucose-transporter expression in insulin-sensitive tissues. Heterogeneous response in heart, red and white muscle

1992 ◽  
Vol 282 (3) ◽  
pp. 765-772 ◽  
Author(s):  
M Camps ◽  
A Castelló ◽  
P Muñoz ◽  
M Monfar ◽  
X Testar ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
White Muscle ◽  
Glucose Transporter ◽  
Mrna Levels ◽  
Glut 4 ◽  
Brown Adipose ◽  
Red Muscle

1. GLUT-4 glucose-transporter protein and mRNA levels were assessed in heart, red muscle and white muscle, as well as in brown and white adipose tissue from 7-day streptozotocin-induced diabetic and 48 h-fasted rats. 2. In agreement with previous data, white adipose tissue showed a substantial decrease in GLUT-4 mRNA and protein levels in response to both diabetes and fasting. Similarly, GLUT-4 mRNA and protein markedly decreased in brown adipose tissue in both insulinopenic conditions. 3. Under control conditions, the level of expression of GLUT-4 protein content differed substantially in heart, red and white skeletal muscle. Thus GLUT-4 protein was maximal in heart, and red muscle had a greater GLUT-4 content compared with white muscle. In spite of the large differences in GLUT-4 protein content, GLUT-4 mRNA levels were equivalent in heart and red skeletal muscle. 4. In heart, GLUT-4 mRNA decreased to a greater extent than GLUT-4 protein in response to diabetes and fasting. In contrast, red muscle showed a greater decrease in GLUT-4 protein than in mRNA in response to diabetes or fasting, and in fact no decrease in GLUT-4 mRNA content was detectable in fasting. On the other hand, preparations of white skeletal muscle showed a substantial increase in GLUT-4 mRNA under both insulinopenic conditions, and that was concomitant to either a modest decrease in GLUT-4 protein in diabetes or to no change in fasting. 5. These results indicate that (a) the effects of diabetes and fasting are almost identical and lead to changes in GLUT-4 expression that are tissue-specific, (b) white adipose tissue, brown adipose tissue and heart respond similarly to insulin deficiency by decreasing GLUT-4 mRNA to a larger extent than GLUT-4 protein, and (c) red and white skeletal muscle respond to insulinopenic conditions in a heterogeneous manner which is characterized by enhanced GLUT-4 mRNA/protein ratios.

Uncoupling Protein-3 mRNA Levels Are Increased in White Adipose Tissue and Skeletal Muscle of Bezafibrate-Treated Rats

1999 ◽  
Vol 260 (2) ◽  
pp. 547-556 ◽  
Author(s):  
Àgatha Cabrero ◽  
Gemma Llaverı́as ◽  
Núria Roglans ◽  
Marta Alegret ◽  
Rosa Sánchez ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
Uncoupling Protein 3

scholarly journals Plasma and cerebrospinal fluid leptin levels are maintained despite enhanced food intake in progesterone-treated rats

2001 ◽  
pp. 659-665 ◽  
Author(s):  
E Grueso ◽  
M Rocha ◽  
M Puerta
Keyword(s):  
Cerebrospinal Fluid ◽  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
White Adipose Tissue ◽  
Mrna Level ◽  
Positive Energy ◽  
Reduce Food Intake ◽  
Mrna Levels ◽  
Fat Depots

OBJECTIVES: For adipostatic control, increases in food intake are followed by increased leptin levels that in turn reduce food intake. However, progesterone administration increases both food intake and body weight. The aim of this study was to analyze changes in the white adipose tissue-leptin system in rats with enhanced plasma levels of progesterone. METHODS: Female Wistar rats received progesterone chronically by means of subcutaneous implants over 30 days. RESULTS: They showed an increased food intake followed by increased body weight and heavier fat depots. An enhanced ob-mRNA level was detected in inguinal white adipose tissue depot on day 2 of treatment but the increase was transient, disappearing on day 6 of treatment. No changes in ob-mRNA levels were found in parametrial and retroperitoneal white adipose tissue depots. Plasma and cerebrospinal fluid leptin levels were unchanged either during the treatment or between corresponding treated and control rats. Leptin concentrations in cerebrospinal fluid were ten times lower than in plasma (0.2--0.3 ng/ml versus 2--3 ng/ml respectively). CONCLUSIONS: These results indicated that progesterone favours a positive energy balance not only by enhancing food intake but also by inhibiting the concurrent enhancement in plasma and cerebrospinal fluid leptin levels expected from the increased fat mass.

scholarly journals Changes in insulin-receptor mRNA levels in skeletal muscle and brown adipose tissue of weanling rats during fasting and refeeding

1992 ◽  
Vol 68 (3) ◽  
pp. 583-592 ◽  
Author(s):  
Rachel M. Knott ◽  
Paul Trayhurn ◽  
John E. Hesketh
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Insulin Receptor ◽  
Uncoupling Protein ◽  
Mrna Level ◽  
Mrna Levels ◽  
Receptor Mrna ◽  
Brown Adipose ◽  
Fasting And Refeeding

Tissue-specific alterations in insulin sensitivity occur in response to fasting and refeeding, as part of the integrated adaptive mechanisms employed to adjust to major changes in nutritional status. In the present study the effects of fasting and refeeding on insulin-receptor, actin and myosin mRNA levels in skeletal muscle, and insulin-receptor and uncoupling-protein mRNA in brown adipose tissue of rats have been examined. Insulin-receptor mRNA levels increased markedly in both skeletal muscle and brown adipose tissue after a 40 h fast, the increase being greater in brown fat (8-fold) than in muscle (2-fold). On refeeding for 4 h, the insulin-receptor mRNA level in both tissues declined rapidly to control levels. An increase in insulin-receptor mRNA level was also observed in brown adipose tissue after a 16 h fast, although not in skeletal muscle. In contrast to the insulin-receptor mRNA, the level of the mRNA for the mitochondrial uncoupling protein declined markedly in brown adipose tissue during a 40 h fast. These results indicate that insulin-receptor mRNA levels are modulated in response to the alterations in nutritional status that occur during fasting and refeeding; this may reflect a nutritional influence on transcription of the receptor-protein gene

scholarly journals Developmental patterns of FASN and LIPE mRNA expression in adipose tissue of growing Jinhua and Landrace gilts

2010 ◽  
Vol 55 (No. 12) ◽  
pp. 557-564 ◽  
Author(s):  
Z. Miao ◽  
F. Zhu ◽  
H. Zhang ◽  
X. Chang ◽  
H. Xie ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid Synthase ◽  
Mrna Level ◽  
Fat Content ◽  
Mrna Levels ◽  
Similar Model ◽  
Rt Pcr ◽  
Developmental Patterns ◽  
Hormone Sensitive ◽  
Subcutaneous Adipose

The present study was aimed to investigate the developmental patterns of FASN (fatty acid synthase) and LIPE (lipase, hormone-sensitive) mRNA in adipose tissue in pigs of different breeds and the relation with carcass fat content. Subcutaneous adipose tissue was sampled and total RNA was extracted to determine FASN and LIPE mRNA levels by semi-quantitative RT-PCR. The results showed that the FASN mRNA level increased with age (P < 0.05) and Jinhua gilts expressed higher FASN mRNA compared with Landrace gilts at 80 and 125 days of age (P < 0.05). In addition, Jinhua gilts expressed lower LIPE mRNA compared with Landrace gilts at 80 days of age (P < 0.01). Furthermore, the ratio of FASN/LIPE mRNA had a similar model in the two breeds, and was higher in Jinhua gilts than that in Landrace gilts at 80 and 125 days of age (P < 0.05). The FASN mRNA level was positively related to carcass fat content in Jinhua and Landrace gilts (r = 0.802, P = 0.01; r = 0.734, P = 0.02; respectively), and the ratio of FASN/LIPE expression exhibited significantly positively related carcass fat content (r = 0.804, P = 0.01; r = 0.749, P = 0.02; respectively).

Improvement of glucose homeostasis and hepatic insulin resistance in ob/ob mice given oral molybdate

1997 ◽  
Vol 155 (1) ◽  
pp. 55-64 ◽  
Author(s):  
BA Reul ◽  
DJ Becker ◽  
LN Ongemba ◽  
CJ Bailey ◽  
JC Henquin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Tyrosine Kinase ◽  
Glucose Homeostasis ◽  
White Adipose Tissue ◽  
Receptor Tyrosine Kinase ◽  
Mrna Level ◽  
Hepatic Insulin Resistance ◽  
Tnf Alpha ◽  
Mrna Levels

Molybdate (Mo) exerts insulinomimetic effects in vitro. In this study, we evaluated whether Mo can improve glucose homeostasis in genetically obese, insulin-resistant ob/ob mice. Oral administration of Mo (174 mg/kg molybdenum element) for 7 weeks did not affect body weight, but decreased the hyperglycaemia (approximately 20 mM) of obese mice to the levels of lean (L) (+/+) mice, and reduced the hyperinsulinaemia to one-sixth of pretreatment levels. Tolerance to oral glucose was improved: total glucose area was 30% lower in Mo-treated mice than in untreated ob/ob mice (O), while the total insulin area was halved. Hepatic glucokinase (GK) mRNA level and activity were unchanged in O mice compared with L mice, but the mRNA level and activity of L-type pyruvate kinase (L-PK) were increased in O mice by 3.5- and 1.7-fold respectively. Mo treatment increased GK mRNA levels and activity (by approximately 2.2-fold and 61% compared with O values), and had no, or only a mild, effect on the already increased L-PK variables. mRNA levels and activity of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK) were augmented in O liver (sixfold and by 57% respectively), and these were reduced by Mo treatment. Insulin binding to partially purified receptors from liver was reduced in O mice and restored by Mo treatment. Despite this correction, overall receptor tyrosine kinase activity was not improved in Mo mice. Moreover, the overexpression (by two- to fourfold) of the cytokine tumour necrosis factor alpha (TNF alpha) in white adipose tissue, which may have a determinant role in the insulin resistance of the O mice, was unaffected by Mo. Likewise, overexpression of the ob gene in white adipose tissue was unchanged by Mo. In conclusion, Mo markedly improved glucose homeostasis in the ob/ob mice by an insulin-like action which appeared to be exerted distal to the insulin receptor tyrosine kinase step. The blood glucose-lowering effect of Mo was unrelated to over-expression of the TNF alpha and ob genes in O mice, but resulted at least in part from attenuation of liver insulin resistance by the reversal of pre-translational regulatory defects in these mice.

Metallothionein gene expression and secretion in white adipose tissue

2000 ◽  
Vol 279 (6) ◽  
pp. R2329-R2335 ◽  
Author(s):  
Paul Trayhurn ◽  
Jacqueline S. Duncan ◽  
Anne M. Wood ◽  
John H. Beattie
Keyword(s):  
Gene Expression ◽  
Molecular Weight ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Stromal Vascular Fraction ◽  
Low Molecular Weight ◽  
Secretory Product ◽  
Mrna Levels ◽  
Gene Encoding ◽  
Adrenoceptor Agonist

White adipose tissue (WAT) has been examined to determine whether the gene encoding metallothionein (MT), a low-molecular-weight stress response protein, is expressed in the tissue and whether MT may be a secretory product of adipocytes. The MT-1 gene was expressed in epididymal WAT, with MT-1 mRNA levels being similar in lean and obese ( ob/ ob) mice. MT-1 mRNA was found in each of the main adipose tissue sites (epididymal, perirenal, omental, subcutaneous), and there was no major difference between depots. Separation of adipocytes from the stromal-vascular fraction of WAT indicated that the MT gene (MT-1 and MT-2) was expressed in adipocytes themselves. Treatment of mice with zinc had no effect on MT-1 mRNA levels in WAT, despite strong induction of MT-1 expression in the liver. MT-1 gene expression in WAT was also unaltered by fasting or norepinephrine. However, administration of a β3-adrenoceptor agonist, BRL-35153A, led to a significant increase in MT-1 mRNA. On differentiation of fibroblastic preadipocytes to adipocytes in primary culture, MT was detected in the medium, suggesting that the protein may be secreted from WAT. It is concluded that WAT may be a significant site of MT production; within adipocytes, MT could play an antioxidant role in protecting fatty acids from damage.

scholarly journals Central Leptin Regulates Total Ceramide Content and Sterol Regulatory Element Binding Protein-1C Proteolytic Maturation in Rat White Adipose Tissue

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 169-178 ◽  
Author(s):  
Elena Bonzón-Kulichenko ◽  
Dominik Schwudke ◽  
Nilda Gallardo ◽  
Eduardo Moltó ◽  
Teresa Fernández-Agulló ◽  
...  
Keyword(s):  
Nervous System ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
White Adipose Tissue ◽  
Binding Protein ◽  
Regulatory Element ◽  
Mrna Levels ◽  
Element Binding Protein ◽  
Ceramide Content ◽  
Sterol Regulatory Element

Obesity and type 2 diabetes are associated with insulin and leptin resistance, and increased ceramide contents in target tissues. Because the adipose tissue has become a central focus in these diseases, and leptin-induced increases in insulin sensitivity may be related to effects of leptin on lipid metabolism, we investigated herein whether central leptin was able to regulate total ceramide levels and the expression of enzymes involved in ceramide metabolism in rat white adipose tissue (WAT). After 7 d central leptin treatment, the total content of ceramides was analyzed by quantitative shotgun lipidomics mass spectrometry. The effects of leptin on the expression of several enzymes of the sphingolipid metabolism, sterol regulatory element binding protein (SREBP)-1c, and insulin-induced gene 1 (INSIG-1) in this tissue were studied. Total ceramide levels were also determined after surgical WAT denervation. Central leptin infusion significantly decreased both total ceramide content and the long-chain fatty acid ceramide species in WAT. Concomitant with these results, leptin decreased the mRNA levels of enzymes involved in de novo ceramide synthesis (SPT-1, LASS2, LASS4) and ceramide production from sphingomyelin (SMPD-1/2). The mRNA levels of enzymes of ceramide degradation (Asah1/2) and utilization (sphingomyelin synthase, ceramide kinase, glycosyl-ceramide synthase, GM3 synthase) were also down-regulated. Ceramide-lowering effects of central leptin were prevented by local autonomic nervous system denervation of WAT. Finally, central leptin treatment markedly increased INSIG-1 mRNA expression and impaired SREBP-1c activation in epididymal WAT. These observations indicate that in vivo central leptin, acting through the autonomic nervous system, regulates total ceramide levels and SREBP-1c proteolytic maturation in WAT, probably contributing to improve the overall insulin sensitivity. Central leptin decreases total ceramide levels and prevents sterol regulatory element binding protein (SREBP-1C) proteolytic maturation in white adipose tissue, and probably, in this way, contributes to improve the overall insulin sensitivity.

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