Placental restriction of fetal growth decreases IGF1 and leptin mRNA expression in the perirenal adipose tissue of late gestation fetal sheep

2008 ◽  
Vol 294 (5) ◽  
pp. R1413-R1419 ◽  
Author(s):  
Jaime A. Duffield ◽  
Tony Vuocolo ◽  
Ross Tellam ◽  
Bernard S. Yuen ◽  
Beverly S. Muhlhausler ◽  
...  

Placental restriction (PR) of fetal growth results in a low birth weight and an increased visceral fat mass in postnatal life. We investigated whether PR alters expression of genes that regulate adipogenesis [IGF1, IGF1 receptor (IGF1R), IGF2, IGF2R, proliferator-activated receptor-γ, retinoid-X-receptor-α], adipocyte metabolism (lipoprotein lipase, G3PDH, GAPDH) and adipokine signaling (leptin, adiponectin) in visceral adipose tissue before birth. PR was induced by removal of the majority of endometrial caruncles in nonpregnant ewes before mating. Fetal blood samples were collected from 116 days gestation, and perirenal visceral adipose tissue (PAT) was collected from PR and control fetuses at 145 days. PAT gene expression was measured by quantitative RT-PCR. PR fetuses had a lower weight (PR 2.90 ± 0.32 kg; control, 5.12 ± 0.24 kg; P < 0.0001), mean gestational arterial Po2 ( P < 0.0001), plasma glucose ( P < 0.01), and insulin concentrations ( P < 0.02), than controls. The expression of IGF1 mRNA in PAT was lower in the PR fetuses (PR, 0.332 ± 0.063; control, 0.741 ± 0.083; P < 0.01). Leptin mRNA expression in PAT was also lower in PR fetuses (PR, 0.077 ± 0.009; control, 0.115 ± 0.013; P < 0.05), although there was no difference in the expression of other adipokine or adipogenic genes in PAT between PR and control fetuses. Thus, restriction of placental and hence, fetal substrate supply results in decreased IGF1 and leptin expression in fetal visceral adipose tissue, which may alter the functional development of the perirenal fat depot and contribute to altered leptin signaling in the growth-restricted newborn and the subsequent emergence of an increased visceral adiposity.

Obesity Facts ◽  
2012 ◽  
Vol 5 (3) ◽  
pp. 452-459 ◽  
Author(s):  
Thais Ortiz Hammes ◽  
Cíntia dos Santos Costa ◽  
Francieli Rohden ◽  
Rogério Margis ◽  
Jussara Carnevale de Almeida ◽  
...  

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 571-571
Author(s):  
Wen-Hao Xu ◽  
Yuan-Yuan Qu ◽  
Jun Wang ◽  
Hai-Liang Zhang ◽  
Dingwei Ye

571 Background: Growing evidence has proved obesity one of the confirmed important etiologic indicators for renal cell carcinoma (RCC). CD36 is underpinned to be involved in adipose absorption, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to investigate the mRNA expression of CD36 in anthropometric measures of adipose tissue and defining its value in predicting prognosis in ccRCC patients. Methods: Real-Time qPCR was detected from 367 paired ccRCC and adjacent normal tissues. Distributions of categorical clinical-pathological data together with levels of CD36 expression were compared with χ2-test. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured by MRI. Pearson’s correlation coefficient was utilized to quantify relations between body mass index (BMI), VAT%, SAT and CD36 expression respectively. Cox regression analysis were developed to address the influence of independent factors on prognostic value. Gene Set Enrichment Analysis (GSEA) was performed to select related genes and pathways from TCGA database. Results: In the current study, we demonstrated that CD36 mRNA was highly expressed in ccRCC tissues, and was found significantly increased in patients with advanced TNM stage ( p= 0.003, p< 0.001, p< 0.001), and high VAT% ( p= 0.004). Pearson’s correlation coefficient indicated CD36 amplification positively correlated with BMI ( r= 0.117, p= 0.025), VAT% ( r= 0.465, p< 0.001), while negatively with SAT ( r= -0.296, p= 0.002). Furthermore, ccRCC patients with elevated CD36 expression held shorter PFS and OS, with HR of 4.873 (3.300-7.196, p< 0.001) and 4.610 (2.956-7.189, p< 0.001). In 104 cases whose MRI scans were available, VAT was significantly correlated with poor PFS and OS. Significant genes were obtained from GSEA, and CD36 was found involved in the most significant pathways including fatty acid metabolism, angiogenesis and TGF-β signaling pathways. Conclusions: In conclusion, our study first reveal that elevated CD36 mRNA expression is positively correlated to distribution of abdominal adipose, particularly VAT%, which, in addition, notably predicts poor prognosis in ccRCC patients.


2006 ◽  
Vol 290 (4) ◽  
pp. R1044-R1051 ◽  
Author(s):  
Sheridan Gentili ◽  
Michael J. Waters ◽  
I. Caroline McMillen

It is unknown whether the JAK/STAT/suppressor of cytokine signaling-3 (SOCS-3) intracellular signaling pathway plays a role in tissue growth and metabolism during fetal life. We investigated whether there is a differential profile of SOCS-3 expression in the liver and perirenal adipose tissue during the period of increased fetal growth in late gestation and the impact of fetal growth restriction on SOCS-3 expression in the fetal liver. We also determined whether basal SOCS-3 expression in the fetal liver and perirenal adipose tissue is regulated by endogenous fetal prolactin (PRL). SOCS-3 mRNA abundance was higher in the liver than in the pancreas, spleen, and kidney of the sheep fetus during late gestation. In the liver, SOCS-3 mRNA expression was increased ( P < 0.05) between 125 ( n = 4) and 145 days ( n = 7) gestation and lower ( P < 0.05) in growth-restricted compared with normally grown fetal sheep in late gestation. The relative expression of SOCS-3 mRNA in the fetal liver was directly related to the mean plasma PRL concentrations during a 48-h infusion of either a dopaminergic agonist, bromocriptine ( n = 7), or saline ( n = 5), such that SOCS-3 mRNA expression was lower when plasma PRL concentrations decreased below ∼20 ng/ml [ y = 0.99 − (2.47/ x) + (4.96/ x2); r2 = 0.91, P < 0.0001, n = 12]. No relationship was shown between the abundance of phospho-STAT5 in the fetal liver and circulating PRL. SOCS-3 expression in perirenal adipose tissue decreased ( P < 0001) between 90–91 ( n = 6) and 140–145 days ( n = 9) gestation and was not related to endogenous PRL concentrations. Thus SOCS-3 is differentially expressed and regulated in key fetal tissues and may play an important and tissue-specific role in the regulation of cellular proliferation and differentiation before birth.


Author(s):  
John F. Odhiambo ◽  
Christopher L. Pankey ◽  
Adel B. Ghnenis ◽  
Stephen P. Ford

Similarities in offspring phenotype due to maternal under- or over-nutrition during gestation have been observed in studies conducted at University of Wyoming. In these studies, ewes were either nutrient-restricted (NR) from early to mid-gestation, or fed an obesogenic diet (MO) from preconception through term. Offspring necropsies occurred at mid-gestation, late-gestation, and after parturition. At mid gestation, body weights of NR fetuses were ~30% lighter than controls, whereas MO fetuses were ~30% heavier than those of controls. At birth, lambs born to NR, MO, and control ewes exhibited similar weights. This was a consequence of accelerated fetal growth rates in NR ewes, and reduced fetal growth rates in MO ewes in late gestation, when compared to their respective controls. These fetal growth patterns resulted in remarkably similar effects of increased susceptibility to obesity, cardiovascular disease, and glucose intolerance in offspring programmed mostly during fetal stages of development. These data provide evidence that maternal under- and over-nutrition similarly induce the development of the same cadre of physical and metabolic problems in postnatal life.


2007 ◽  
Vol 293 (4) ◽  
pp. E958-E964 ◽  
Author(s):  
Gregory R. Steinberg ◽  
Bruce E. Kemp ◽  
Matthew J. Watt

We have investigated the gene and protein expression of adipose triglyceride lipase (ATGL) and triglyceride (TG) lipase activity from subcutaneous and visceral adipose tissue of lean and obese subjects. Visceral and subcutaneous adipose tissue was obtained from 16 age-matched lean and obese subjects during abdominal surgery. Tissues were analyzed for mRNA expression of lipolytic enzymes by real-time quantitative PCR. ATGL protein content was assessed by Western blot and TG lipase activity by radiometric assessment. Subcutaneous and visceral adipose tissue of obese subjects had elevated mRNA expression of PNPLA2 (ATGL) and other lipases including PNPLA3, PNPLA4, CES1, and LYPLAL1 ( P < 0.05). Surprisingly, ATGL protein expression and TG lipase activity were reduced in subcutaneous adipose tissue of obese subjects. Immunoprecipitation of ATGL reduced total TG lipase activity in adipose lysates by 70% in obese and 83% in lean subjects. No significant differences in the ATGL activator CGI-58 mRNA levels ( ABHD5) were associated with obesity. These data demonstrate that ATGL is important for efficient TG lipase activity in humans. They also demonstrate reduced ATGL protein expression and TG lipase activity despite increased mRNA expression of ATGL and other novel lipolytic enzymes in obesity. The lack of correlation between ATGL protein content and in vitro TG lipase activity indicates that small decrements in ATGL protein expression are not responsible for the reduction in TG lipase activity observed here in obesity, and that posttranslational modifications may be important.


2020 ◽  
Author(s):  
Jiao Li ◽  
Xu-Fang Liang ◽  
Muhammad Shoaib Alam ◽  
Haocan Luo ◽  
Yanpeng Zhang ◽  
...  

Abstract Background: Chinese perch, a carnivorous fish, can accept artificial diet after domestication nowadays, and this farm way will gain high economic interest and sustainability. However, the high content and high quality requirement of dietary protein make it need the high cost in Chinese perch. Therefore, the aim of this study was to explore the effect of fish meal replacement by low- or high-rapeseed meal on growth performance, feeding, lipid and glucose metabolism. Methods: Three experimental diets were formulated with 0, 10% and 30% rapeseed meal, named as control, RSL and RSH, groups respectively. After the 8-week of feeding trial, growth performance, lipid metabolism and AMPK-mTOR-signal pathways were measured. Results: Chinese perch fed with RSH and RSL diets showed significantly decreased WG, SGR, BFR, VSI, MSI and the whole-body crude lipid compared to those fed with the control diet (P < 0.05). Fish in RSL group decreased feed intake, serum LDL-C, hepatic mRNA expression of LPL, PEPCK and phosphorylated Grb10 (P < 0.05). In visceral adipose tissue, mRNA expression of FAS, SREBP1, ACC1, HL, CPT1 and PEPCK were all significantly down-regulated (P < 0.05). Fish in RSH group showed phosphorylated AMPK, hepatic mRNA expression of SREBP1, ACC1, FAS, PPARα and CPT1 were down-regulated, while HSL, G6PD and PC were up-regulated (P < 0.05). In visceral adipose tissue, mRNA expressions of SREBP1, LPL, CPT1 and PEPCK were down-regulated, while mRNA expression of HSL was up-regulated (P < 0.05). Conclusions: Chinese perch fed with RSL and RSH diets showed decreased fat deposition in viscera. Fish fed with low level of rapeseed meal diet ate less diet, which caused inhibited lipid metabolism in the liver and visceral adipose tissues.Fish fed with high level of rapeseed meal diet inhibited hepatic FA synthesis, activated lipolysis, hence reducing Acetyl-CoA pool. In turn, β-oxidation were inhibited, glycolysis was activated, thus lipid accumulation was decreased. In visceral adipose tissue, lipid uptake was inhibited, caused inhibited FA synthesis, β-oxidation, glycerol synthesis, and improved lipolysis.


2017 ◽  
Vol 131 (13) ◽  
pp. 1529-1540 ◽  
Author(s):  
Shahzya S. Huda ◽  
Fiona Jordan ◽  
Jack Bray ◽  
Gillian Love ◽  
Reba Payne ◽  
...  

Obesity increases pre-eclampsia (PE) risk. Adipose tissue inflammation may contribute to the clinical syndrome of PE. We compared adipose tissue macrophage infiltration and release of pro-inflammatory adipokines in PE and healthy pregnancy. Subcutaneous and visceral adipose tissue biopsies were collected from healthy (n=13) and PE (n=13) mothers. Basal and lipopolysaccharide (LPS) stimulated adipocyte TNFα, IL-6, CCL-2, and CRP release was measured. Adipose tissue cell densities of activated (cfms+) and total (CD68+) macrophages were determined. In PE only, visceral adipose tissue TNFα release was increased after LPS stimulation (57 [76] versus 81 [97] pg/ml/µg DNA, P=0.030). Basal TNFα release was negatively correlated insulin sensitivity of visceral adipocytes (r = −0.61, P=0.030) in PE. Visceral adipocyte IL-6 release was increased after LPS stimulation in PE only (566 [696] versus 852 [914] pg/ml/µg DNA, P=0.019). Visceral adipocyte CCL-2 basal (67 [61] versus 187 [219] pg/ml/µgDNA, P=0.049) and stimulated (46 [46] versus 224 [271] pg/ml/µg DNA, P=0.003) release was greater than in subcutaneous adipocytes in PE only. In PE, median TNF mRNA expression in visceral adipose tissue was higher than controls (1.94 [1.13–4.14] versus 0.8 [0.00–1.27] TNF/PPIA ratio, P=0.006). In visceral adipose tissue, CSF1R (a marker of activated macrophages) mRNA expression (24.8[11.0] versus 51.0[29.9] CSF1R/PPIA ratio, P=0.011) and activated (cfms+) macrophage count (6.7[2.6] versus 15.2[8.8] % cfms+/adipocyte, P=0.031) were higher in PE than in controls. In conclusion, our study demonstrates dysregulation of inflammatory pathways predominantly in visceral adipose tissue in PE. Inflammation of visceral adipose tissue may mediate many of the adverse metabolic effects associated with PE.


2011 ◽  
Vol 164 (4) ◽  
pp. 539-547 ◽  
Author(s):  
Ximena Terra ◽  
Yunuen Quintero ◽  
Teresa Auguet ◽  
Jose Antonio Porras ◽  
Mercé Hernández ◽  
...  

ObjectiveThe adipocyte/macrophage fatty acid-binding protein 4 (FABP4) has been described as a biomarker for adiposity and metabolic syndrome (MS). The aims of this study were to assess the relationship between FABP4 and inflammatory cytokines related to obesity, and to evaluate FABP4 mRNA expression in visceral and subcutaneous adipose tissue in non-diabetic morbidly obese women versus healthy lean women.MethodsWe analyzed circulating levels of FABP4 in 81 Spanish women: 38 lean (body mass index (BMI)<25 kg/m2) and 43 morbidly obese (BMI>40 kg/m2). We took 30 follow-up blood samples at 6 and 12 months after bariatric surgery. We assessed FABP4 gene expression in samples of subcutaneous abdominal and visceral adipose tissue. Adipose tissue mRNA expression was determined by real-time RT-PCR.ResultsIn morbidly obese women, plasma FABP4 levels were significantly higher than in non-obese patients. These levels positively correlated with BMI, homeostasis model assessment of insulin resistance (HOMA2-IR), and plasma glucose and insulin levels. Post-operative FABP4 levels decreased by a maximum of 30% after 12 months. We also found an inverse association between FABP4 and adiponectin levels, and positive correlations between FABP4 and circulating leptin, tumor necrosis factor (TNF) receptors, C-reactive protein (CRP) and interleukin 6 levels. Linear regression analysis revealed that FABP4 was more closely related to HOMA2-IR than adiponectin, CRP, TNF-RI, or leptin. Furthermore, high circulating FABP4 levels were associated with the presence of MS. FABP4 mRNA expression in visceral adipose tissue was related to its circulating levels in morbidly obese women.ConclusionsOur results indicate that serum FABP4 is associated with inflammatory factors related to obesity and MS in non-diabetic morbidly obese women.


2020 ◽  
Vol 93 (1112) ◽  
pp. 20200334
Author(s):  
Federico Greco ◽  
Luigi Giuseppe Quarta ◽  
Rosario Francesco Grasso ◽  
Bruno Beomonte Zobel ◽  
Carlo Augusto Mallio

Objective: The excessive amount of adipose tissue, mainly visceral, determines adiposopathy. With respect to oncogenesis, visceral adipose tissue (VAT) releases secretes adipokines, proinflammatory citokines and growth factors, considered mediating molecules in the development of obesity-related tumors. In this study, we quantify VAT in male patients with clear cell renal cell carcinoma (ccRCC) subgrouped according to the presence or absence of peritumoral collateral vessels. Methods: in this retrospective study, we enrolled 141 male caucasian patients divided into 2 groups: the ccRCC group (n = 106) composed of patients with ccRCC and control group (n = 35). The ccRCC group was further divided into two subgroups: the ccRCCa subgroup which showed absence of collateral vessels (n = 48) and ccRCCp subgroup with collateral vessels (n = 58). Total adipose tissue (TAT) area, VAT area and subcutaneous adipose tissue (SAT) area were measured in the groups and subgroups. VAT/SAT ratio was calculated for each subject. Results: Statistically significant differences were obtained between ccRCC group and control group for TAT area (p < 0.005), VAT area (p < 0.005) and SAT area (p = 0.01). Between ccRCCa subgroup and control group for TAT area (p < 0.001), VAT area (p = 0.005) and SAT area (p = 0.001). Between ccRCCp subgroup and control group for TAT area (p = 0.01) and VAT area (p = 0.01). Conclusion: This study confirms the increase of abdominal, especially visceral, adipose tissue in ccRCC patients and demonstrates a significant VAT accumulation in both categories of patients with and without peritumoral collateral vessels. Advances in knowledge: Visceral adiposity is present in patients with ccRCC regardless the presence of peritumoral collateral vessels, with surprisingly stronger results in the ccRCCa subgroup.


2014 ◽  
Vol 9 (S 01) ◽  
Author(s):  
T Wohland ◽  
D Schleinitz ◽  
M Kern ◽  
M Prellberg ◽  
J Breitfeld ◽  
...  

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