Expression of Genes Related to Prostaglandin Synthesis or Signaling in Human Subcutaneous and Omental Adipose Tissue: Depot Differences and Modulation by Adipogenesis

Objectives. (1) To examine depot-specific PGE2and PGF2αrelease and mRNA expression of enzymes or receptors involved in PG synthesis or signaling in human adipose tissues; (2) to identify changes in expression of these transcripts through preadipocyte differentiation; and (3) to examine associations between adipose tissue mRNA expression of these transcripts and adiposity measurements.Methods. Fat samples were obtained surgically in women. PGE2and PGF2αrelease by preadipocytes and adipose tissue explants was measured. Expression levels of mRNA coding for enzymes or receptors involved in PG synthesis or signaling were measured by RT-PCR.Results. Cultured preadipocytes and explants from omental fat released more PGE2and PGF2αthan those from the subcutaneous depot and the corresponding transcripts showed consistent depot differences. Following preadipocyte differentiation, expression of PLA2G16 and PTGER3 mRNA was significantly increased whereas COX-1, COX-2, PTGIS, and PTGES mRNA abundance were decreased in both compartments (P≤0.01for all). Transcripts that were stimulated during adipogenesis were those that correlated best with adiposity measurements.Conclusion. Cells from the omental fat compartment release more PGE2and PGF2αthan those from the subcutaneous depot. Obesity modulates expression of PG-synthesizing enzymes and PG receptors which likely occurs through adipogenesis-induced changes in expression of these transcripts.

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Hyperglycemia-induced changes in resistin gene expression in white adipose tissue in piglets

Annals of Animal Science ◽

10.1515/aoas-2015-0021 ◽

2015 ◽

Vol 15 (3) ◽

pp. 667-679 ◽

Cited By ~ 2

Author(s):

Ewa Ocłoń ◽

Joanna Zubel-Łojek ◽

Anna Latacz ◽

Krystyna Pierzchała-Koziec

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Opposite Effect ◽

Mrna Level ◽

Physiological Saline ◽

Glycemic Status ◽

Omental Adipose Tissue ◽

Induced Changes ◽

Omental Fat ◽

Resistin Mrna

Abstract Previous data strongly indicated that resistin, an adipocyte-derived signalling peptide, plays an important role in metabolism and glucose homeostasis. Thus, the aim of the present study was to examine changes in synthesis and concentration of resistin in white adipose tissue in response to hyperglycemia in piglets. In order to develop hyperglycemia, piglets (10-week-old, Polish Landrace fatteners, female) received intraperitoneal (ip) injection of 150 mg streptozotocin (HI, n=6) or 60 mg synthetic glucocorticoid (HII, n=6). An injection of NaCl physiological saline was used as a control (n=6). Plasma resistin level was significantly higher in HII group compared with the control, while no difference was observed in HI. In epicardial adipose tissue (EAT ) the resistin mRNA level significantly increased whereas the opposite effect was observed for omental fat tissue (OAT ) in both experimental groups. Additionally, the resistin concentration did not change in EAT ; however, it was decreased in omental adipose tissue in response to hyperglycemia. The results obtained indicate that activity of resistin strongly depends on glycemic status as well as adipose tissue localization.

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Glucocorticoid-induced androgen inactivation by aldo-keto reductase 1C2 promotes adipogenesis in human preadipocytes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00069.2011 ◽

2012 ◽

Vol 302 (8) ◽

pp. E941-E949 ◽

Cited By ~ 23

Author(s):

Alain Veilleux ◽

Julie-Anne Côté ◽

Karine Blouin ◽

Mélanie Nadeau ◽

Mélissa Pelletier ◽

...

Keyword(s):

Adipose Tissue ◽

Lipid Accumulation ◽

Tissue Sample ◽

Subcutaneous Fat ◽

Human Adipose Tissue ◽

Preadipocyte Differentiation ◽

Omental Adipose Tissue ◽

Human Preadipocytes ◽

Omental Fat ◽

G3pdh Activity

Adipogenesis and lipid storage in human adipose tissue are inhibited by androgens such as DHT. Inactivation of DHT to 3α-diol is stimulated by glucocorticoids in human preadipocytes. We sought to characterize glucocorticoid-induced androgen inactivation in human preadipocytes and to establish its role in the antiadipogenic action of DHT. Subcutaneous and omental primary preadipocyte cultures were established from fat samples obtained in subjects undergoing abdominal surgeries. Inactivation of DHT to 3α/β-diol for 24 h was measured in dexamethasone- or vehicle-treated cells. Specific downregulation of aldo-keto reductase 1C (AKR1C) enzymes in human preadipocytes was achieved using RNA interference. In whole adipose tissue sample, cortisol production was positively correlated with androgen inactivation in both subcutaneous and omental adipose tissue ( P < 0.05). Maximal dexamethasone (1 μM) stimulation of DHT inactivation was higher in omental compared with subcutaneous fat from men as well as subcutaneous and omental fat from women ( P < 0.05). A significant positive correlation was observed between BMI and maximal dexamethasone-induced DHT inactivation rates in subcutaneous and omental adipose tissue of men and women ( r = 0.24, n = 26, P < 0.01). siRNA-induced downregulation of AKR1C2, but not AKR1C1 or AKR1C3, significantly reduced basal and glucocorticoid-induced androgen inactivation rates ( P < 0.05). The inhibitory action of DHT on preadipocyte differentiation was potentiated following AKR1C2 but not AKR1C1 or AKR1C3 downregulation. Specifically, lipid accumulation, G3PDH activity, and FABP4 mRNA expression in differentiated preadipocytes exposed to DHT were reduced further upon AKR1C2 siRNA transfection. We conclude that glucocorticoid-induced androgen inactivation is mediated by AKR1C2 and is particularly effective in omental preadipocytes of obese men. The interplay between glucocorticoids and AKR1C2-dependent androgen inactivation may locally modulate adipogenesis and lipid accumulation in a depot-specific manner.

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Expression of genes related to glucocorticoid action in human subcutaneous and omental adipose tissue

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/j.jsbmb.2010.02.024 ◽

2010 ◽

Vol 122 (1-3) ◽

pp. 28-34 ◽

Cited By ~ 37

Author(s):

Alain Veilleux ◽

Philippe Y. Laberge ◽

Jacques Morency ◽

Suzanne Noël ◽

Van Luu-The ◽

...

Keyword(s):

Adipose Tissue ◽

Omental Adipose Tissue ◽

Expression Of Genes ◽

Glucocorticoid Action

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Neudesin Neurotrophic Factor Promotes Bovine Preadipocyte Differentiation and Inhibits Myoblast Myogenesis

Animals ◽

10.3390/ani9121109 ◽

2019 ◽

Vol 9 (12) ◽

pp. 1109 ◽

Cited By ~ 1

Author(s):

Xiaotong Su ◽

Yaning Wang ◽

Anqi Li ◽

Linsen Zan ◽

Hongbao Wang

Keyword(s):

Adipose Tissue ◽

Protein Expression ◽

Mrna Expression ◽

Neurotrophic Factor ◽

Muscle Development ◽

Expression Patterns ◽

Marker Genes ◽

Qinchuan Cattle ◽

Preadipocyte Differentiation ◽

Expression Levels

Neudesin neurotrophic factor (NENF) is a secreted protein that is essential in multiple biological processes, including neural functions, adipogenesis, and tumorigenesis. In our previous study, NENF was significantly inhibited in the bovine adipocytes-myoblasts co-culture system. However, studies on NENF regulation of bovine muscle development and involvement in the cross-talk between adipose tissue and skeletal muscle have not been reported. Hence, the aim of this study was to clarify the functional roles of NENF in bovine preadipocytes and myoblasts. Real-time quantitative PCR (RT-qPCR) was performed to examine the spatial expression patterns of NENF in different tissues, and the results showed that NENF was highly expressed in the muscle of four-day-old and 24-month-old Qinchuan cattle. Compared with four-day-old Qinchuan cattle, the expression level of NENF was significantly up-regulated in 24-month-old bovine adipose tissue. To explore the roles of NENF in bovine myoblast and preadipocyte differentiation, small interfering RNA (siRNA) targeting the NENF gene were transfected into bovine preadipocytes and myoblasts to knock down the expression of the NENF gene. The results showed that the knockdown of NENF in differentiating adipocytes attenuated lipid accumulation, decreased the mRNA expression of adipogenic key marker genes PPARγ, CEBPα, CEBPβ, FASN, and SCD1, and decreased the protein expression of PPARγ, CEBPα, and FASN. The formation of myotubes was significantly accelerated, and the mRNA expression levels of myogenic marker genes MYOD1, MYF5, MYF6, MEF2A, MEF2C, and CKM, and the protein expression levels of MYOD1, MYF6, MEF2A, and CKM were up-regulated in myoblasts where NENF was knocked down. In short, the knockdown of NENF inhibited preadipocyte differentiation and promoted myoblast myogenesis.

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Androgen generation in adipose tissue in women with simple obesity – a site-specific role for 17β-hydroxysteroid dehydrogenase type 5

Journal of Endocrinology ◽

10.1677/joe.1.05762 ◽

2004 ◽

Vol 183 (2) ◽

pp. 331-342 ◽

Cited By ~ 89

Author(s):

Marcus Quinkler ◽

Binayak Sinha ◽

Jeremy W Tomlinson ◽

Iwona J Bujalska ◽

Paul M Stewart ◽

...

Keyword(s):

Weight Loss ◽

Adipose Tissue ◽

Subcutaneous Fat ◽

Human Adipose Tissue ◽

Hydroxysteroid Dehydrogenase ◽

Rt Pcr ◽

Androgen Synthesis ◽

The Metabolic Syndrome ◽

Simple Obesity ◽

Omental Fat

Women with polycystic ovary syndrome (PCOS) have high circulating androgens, thought to originate from ovaries and adrenals, and frequently suffer from the metabolic syndrome including obesity. However, serum androgens are positively associated with body mass index (BMI) not only in PCOS, but also in simple obesity, suggesting androgen synthesis within adipose tissue. Thus we investigated androgen generation in human adipose tissue, including expression of 17β-hydroxysteroid dehydrogenase (17β-HSD) isozymes, important regulators of sex steroid metabolism. Paired omental and subcutaneous fat biopsies were obtained from 27 healthy women undergoing elective abdominal surgery (age range 30–50 years; BMI 19.7–39.2 kg/m2). Enzymatic activity assays in preadipocyte proliferation cultures revealed effcient conversion of androstenedione to testosterone in both subcutaneous and omental fat. RT-PCR of whole fat and preadipocytes of subcutaneous and omental origin showed expression of 17β-HSD types 4 and 5, but no relevant expression of 17β-HSD types 1, 2, or 3. Microarray analysis confirmed this expression pattern (17β-HSD5>17β-HSD4) and suggested a higher expression of 17β-HSD5 in subcutaneous fat. Accordingly, quantitative real-time RT-PCR showed significantly higher expression of 17β-HSD5 in subcutaneous compared with omental fat (P<0.05). 17β-HSD5 expression in subcutaneous, but not omental, whole fat correlated significantly with BMI (r=0.51, P<0.05). In keeping with these findings, 17β-HSD5 expression in subcutaneous fat biopsies from six women taking part in a weight loss study decreased significantly with weight loss (P<0.05). A role for 17β-HSD5 in adipocyte differentiation was further supported by the observed increase in 17β-HSD5 expression upon differentiation of stromal preadipocytes to mature adipocytes (n=5; P<0.005), which again was higher in cells of subcutaneous origin. Functional activity of 17β-HSD5 also significantly increased with differentiation, revealing a net gain in androgen activation (androstenedione to testosterone) in subcutaneous cultures, contrasting with a net gain in androgen inactivation (testosterone to androstenedione) in omental cultures. Thus, human adipose tissue is capable of active androgen synthesis catalysed by 17β-HSD5, and increased expression in obesity may contribute to circulating androgen excess.

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The effect of placental restriction on insulin signaling and lipogenic pathways in omental adipose tissue in the postnatal lamb

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174413000202 ◽

2013 ◽

Vol 4 (5) ◽

pp. 421-429 ◽

Cited By ~ 4

Author(s):

S. Lie ◽

J. A. Duffield ◽

I. C. McMillen ◽

J. L. Morrison ◽

S. E. Ozanne ◽

...

Keyword(s):

Adipose Tissue ◽

Mrna Expression ◽

Insulin Signaling ◽

Visceral Obesity ◽

Signaling Molecules ◽

Protein Abundance ◽

Adipose Depot ◽

Omental Adipose Tissue ◽

Lipogenic Genes ◽

Neonatal Lambs

Intrauterine growth restriction (IUGR) followed by accelerated growth after birth is associated with an increased risk of abdominal (visceral) obesity and insulin resistance in adult life. The aim of the present study was to determine the impact of IUGR on mRNA expression and protein abundance of insulin signaling molecules in one of the major visceral fat depots, the omental adipose depot. IUGR was induced by placental restriction, and samples of omental adipose tissue were collected from IUGR (n = 9, 5 males, 4 females) and Control (n = 14, 8 males, 6 females) neonatal lambs at 21 days of age. The mRNA expression of the insulin signaling molecules, AMP-kinase (AMPK) and adipogenic/lipogenic genes was determined by qRT-PCR, and protein abundance by Western Blotting. AMPKα2 mRNA expression was increased in male IUGR lambs (0.015 ± 0.002 v. 0.0075 ± 0.0009, P < 0.001). The proportion of the AMPK pool that was phosphorylated (%P-AMPK) was lower in IUGR lambs compared with Controls independent of sex (39 ± 9% v. 100 ± 18%, P < 0.001). The mRNA expression and protein abundance of insulin signaling proteins and adipogenic/lipogenic genes was not different between groups. Thus, IUGR is associated with sex-specific alterations in the mRNA expression of AMPKα2 and a reduction in the percentage of the total AMPK pool that is phosphorylated in the omental adipose tissue of neonatal lambs, before the onset of visceral obesity. These molecular changes would be expected to promote lipid accumulation in the omental adipose depot and may therefore contribute to the onset of visceral adiposity in IUGR animals later in life.

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Synergetic Action of Forskolin and Mevastatin Induce Normalization of Lipids Profile in Dyslipidemic Rats through Adenosine Monophosphate Kinase Upregulation

BioMed Research International ◽

10.1155/2021/6687551 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Aaser M. Abdelazim ◽

Tamer Ahmed Ismail ◽

Mosleh M. Abumaghaid ◽

Islam M. Saadaldin

Keyword(s):

Adipose Tissue ◽

Lipid Metabolism ◽

Lipid Profile ◽

Mrna Expression ◽

Synergetic Effect ◽

Adenosine Monophosphate ◽

Hormone Sensitive Lipase ◽

Albino Rats ◽

Omental Adipose Tissue ◽

Triton Wr 1339

In the present study, we examined the synergetic effect of forskolin and mevastatin administration on lipid profile and lipid metabolism in omental adipose tissue in dyslipidemic rats. The study was conducted on forty male albino rats. The rats were randomly classified into four main groups of ten animals in each group as follows: group A, served as control nontreated; group B, rats that received Triton WR 1339 (500 mg/kg); group C, rats that received Triton WR 1339 with forskolin (100% FSK extract 0.5 mg/kg/day) for four weeks; and group D, dyslipidemic rats received both mevastatin and forskolin. At the end of the experimental period, blood and omental adipose tissue samples were collected, preserved, and used for biochemical determination of lipid profile and mRNA expression profile of adenylate cyclase (AC), hormone-sensitive lipase, respectively (HSL), and adenosine monophosphate-activated protein kinase (AMPK). The results showed a significant decline in the serum concentration of total cholesterol, LDL-cholesterol, and triglycerides, although there was a significant increase in serum levels of HDL-cholesterol and glycerol in rats received forskolin alone or with mevastatin when compared with control and dyslipidemic groups. The mRNA expression levels of AC, HSL, and AMPK were significantly increased in omental adipose tissue of rats received forskolin when compared with other groups. In conclusion, forskolin acts synergistically with mevastatin to lower lipid profile and improve lipid metabolism in dyslipidemic rats through upregulation of AMPK expression.

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FAT/CD36 regulates PEPCK expression in adipose tissue

AJP Cell Physiology ◽

10.1152/ajpcell.00372.2012 ◽

2013 ◽

Vol 304 (5) ◽

pp. C478-C484 ◽

Cited By ~ 17

Author(s):

Zhongxiao Wan ◽

Sarthak Matravadia ◽

Graham P. Holloway ◽

David C. Wright

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Mrna Expression ◽

Phosphoenolpyruvate Carboxykinase ◽

Fatty Acid Uptake ◽

Acid Oxidation ◽

Acid Uptake ◽

Expression Of Genes ◽

Fatty Acid Release ◽

Acid Release

Fatty acid translocase (FAT)/CD36 has been extensively studied for its role in facilitating fatty acid uptake. Recent findings have also demonstrated that this protein regulates adipocyte lipolysis and may modulate fatty acid reesterification. As FAT/CD36 has been shown to control the expression of genes involved in fatty acid oxidation in adipocytes, we reasoned that this protein might also control the expression of enzymes involved in fatty acid reesterification. In adipose tissue from FAT/CD36 knockout (KO) mice, we found that glycerol and fatty acid release were reduced and this was associated with reductions in adipose triglyceride lipase. Decreases in lipolysis were paralleled by increases in the free fatty acid-to-glycerol ratio and reductions in primary and fractional rates of fatty acid reesterfication in cultured adipose tissue from FAT/CD36 KO mice. Reductions in reesterfication were associated with decreases in the mRNA expression and protein content of phosphoenolpyruvate carboxykinase (PEPCK). To determine if reductions in lipolysis could lead to decreases in PEPCK mRNA expression, we treated cultured mouse adipose tissue with the lipase inhibitor CAY10499 (2 μM) and found that this resulted in an ∼50% reduction in PEPCK mRNA expression. Treatment with hexarelin (10 μM, 12 h), a CD36 agonist, increased PEPCK mRNA expression independent of lipolysis. Collectively, our results provide novel evidence that FAT/CD36 regulates PEPCK in adipose tissue and that this could be secondary to reductions in lipolysis.

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