The effect of maternal obesity on fatty acid transporter expression and lipid metabolism in the full-term placenta of lean breed swine

2017 ◽  
Vol 102 (1) ◽  
pp. e242-e253 ◽  
Author(s):  
L. Tian ◽  
S. S. Dong ◽  
J. Hu ◽  
J. J. Yao ◽  
P. S. Yan
2017 ◽  
Vol 32 (6) ◽  
pp. 971-978 ◽  
Author(s):  
Xiaohua Yang ◽  
Patricia Glazebrook ◽  
Geraldine C. Ranasinghe ◽  
Maricela Haghiac ◽  
Virtu Calabuig-Navarro ◽  
...  

2020 ◽  
Author(s):  
Ada Admin ◽  
Tim Benninghoff ◽  
Lena Espelage ◽  
Samaneh Eickelschulte ◽  
Isabel Zeinert ◽  
...  

The two closely related RabGTPase-activating proteins (RabGAPs) TBC1D1 and TBC1D4 play a crucial role in the regulation of GLUT4 translocation in response to insulin and contraction in skeletal muscle. In mice, deficiency in one or both RabGAPs leads to reduced insulin and contraction-stimulated glucose uptake, and to elevated fatty acid uptake and oxidation in both glycolytic and oxidative muscle fibers without altering mitochondrial copy number and the abundance of OXPHOS proteins. Here we present evidence for a novel mechanism of skeletal muscle lipid utilization involving the two RabGAPs and the fatty acid transporter SLC27A4/FATP4. Both RabGAPs control the uptake of saturated and unsaturated long-chain fatty acids (LCFAs) into skeletal muscle and knockdown of a subset of RabGAP substrates, <i>Rab8, Rab10 </i>or <i>Rab14, </i>decreased LCFA uptake into these cells. In skeletal muscle from <i>Tbc1d1/Tbc1d4</i> knockout animals, SLC27A4/FATP4 abundance was increased and depletion of SLC27A4/FATP4 but not FAT/CD36 completely abrogated the enhanced fatty acid oxidation in RabGAP-deficient skeletal muscle and cultivated C2C12 myotubes. Collectively, our data demonstrate that RabGAP-mediated control of skeletal muscle lipid metabolism converges with glucose metabolism at the level of downstream RabGTPases and involves regulated transport of LCFAs via SLC27A4/FATP4.


2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Bartlomiej Lukaszuk ◽  
Agnieszka Miklosz ◽  
Malgorzata Zendzian-Piotrowska ◽  
Beata Wojcik ◽  
Jan Gorski ◽  
...  

The diaphragm is a dome-shaped skeletal muscle indispensable for breathing. Its activity contributes up to 70% of the total ventilatory function at rest. In comparison to other skeletal muscles, it is distinguished by an oxidative phenotype and uninterrupted cyclic contraction pattern. Surprisingly, the research regarding diaphragm diabetic phenotype particularly in the light of lipid-induced insulin resistance is virtually nonexistent. Male Wistar rats were randomly allocated into 3 groups: control, streptozotocin-induced (STZ) type-1 diabetes, and rodents fed with high-fat diet (HFD). Additionally, half of the animals from each group were administered with myriocin, a robust, selective inhibitor of ceramide synthesis and, therefore, a potent agent ameliorating insulin resistance. Diaphragm lipid contents were evaluated using chromatography. Fatty acid transporter expression was determined by Western blot. The STZ and HFD rats had increased concentration of lipids, namely, ceramides (CER) and diacylglycerols (DAG). Interestingly, this coincided with an increased concentration of long-chain (C ≥ 16) saturated fatty acid species present in both the aforementioned lipid fractions. The CER/DAG accumulation was accompanied by an elevated fatty acid transporter expression (FATP-1 in HFD and FATP-4 in STZ). Surprisingly, we observed a significantly decreased triacylglycerol content in the diaphragms of STZ-treated rats.


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2768
Author(s):  
Livia Belcastro ◽  
Carolina S. Ferreira ◽  
Marcelle A. Saraiva ◽  
Daniela B. Mucci ◽  
Antonio Murgia ◽  
...  

The rise in prevalence of obesity in women of reproductive age in developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health. Placental lipid metabolism is disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism in women with pre-gestational obesity as a sole pregnancy complication and compared it to placental responses of lean women. Open profile and targeted lipidomics were used to assess placental lipids and oxidised products of docosahexahenoic acid (DHA), neuroprostanes, arachidonic acid (AA), and isoprostanes. Despite no overall signs of lipid accumulation, DHA and AA levels in placentas from obese women were, respectively, 2.2 and 2.5 times higher than those from lean women. Additionally, a 2-fold increase in DHA-derived neuroprostanes and a 1.7-fold increase in AA-derived isoprostanes were seen in the obese group. These changes correlated with a 70% decrease in placental FABP1 protein. Multivariate analyses suggested that neuroprostanes and isoprostanes are associated with maternal and placental inflammation and with birth weight. These results might shed light on the molecular mechanisms associated with altered placental fatty acid metabolism in maternal pre-gestational obesity, placing these oxidised fatty acids as novel mediators of placental function.


2020 ◽  
Vol 10 (9) ◽  
pp. 1282-1295 ◽  
Author(s):  
Gretchen M. Alicea ◽  
Vito W. Rebecca ◽  
Aaron R. Goldman ◽  
Mitchell E. Fane ◽  
Stephen M. Douglass ◽  
...  

2010 ◽  
Vol 299 (5) ◽  
pp. R1224-R1231 ◽  
Author(s):  
Mei J. Zhu ◽  
Yan Ma ◽  
Nathan M. Long ◽  
Min Du ◽  
Stephen P. Ford

Obesity of women at conception is increasing, a condition associated with offspring obesity. We hypothesized that maternal obesity increases placental fatty acid transporter (FATP) expression, enhancing delivery of fatty acids to their fetuses. Sheep are a commonly utilized biomedical model for pregnancy studies. Nonpregnant ewes were randomly assigned to a control group [100% of National Research Council (NRC) recommendations] or obese group (OB, 150% of NRC) from 60 days before conception to 75 or 135 days of gestation (dG; term = 150 dG), when placental cotyledonary tissue was collected for analysis. Fetuses of OB ewes were markedly heavier ( P < 0.05) on 75 dG than fetuses from control ewes, but this difference disappeared by 135 dG. Maternal obesity markedly increased ( P < 0.05) cholesterol and triglyceride concentrations of both maternal and fetal blood. There is no difference in lipoprotein lipase mRNA expression between control and OB group at either gestational age. On 75 dG, the mRNA expression of FATP1 ( P < 0.05), FATP4 ( P = 0.08), and fatty acid translocase CD (cluster of differentiation) 36 ( P < 0.05) proteins were more enhanced in cotyledonary tissue from OB than control ewes; consistently, protein expression of FATP1 and FATP4 was increased ( P < 0.05). Similarly, on 135 dG, the mRNA levels of FATP1, FATP4, and CD36 were all higher ( P < 0.05), but only FATP4 protein content was enhanced ( P < 0.05) in OB cotyledonary tissue. Peroxisome proliferator-activated receptor (PPAR)-γ regulates the expression of FATPs. Both the mRNA expression and protein content of PPARγ were increased in OB cotyledonary in the midgestation. In conclusion, maternal obesity enhances the mRNA expression and protein content of FATPs in cotyledonary in the midgestation, which is associated with higher PPARγ content in cotyledonary.


Placenta ◽  
2016 ◽  
Vol 45 ◽  
pp. 132
Author(s):  
Xiaohua Yang ◽  
Patricia Glazebrook ◽  
Maricela Haghiac ◽  
Judi Minium ◽  
Sylvie Hauguel deMouzon ◽  
...  

2020 ◽  
Author(s):  
Ada Admin ◽  
Tim Benninghoff ◽  
Lena Espelage ◽  
Samaneh Eickelschulte ◽  
Isabel Zeinert ◽  
...  

The two closely related RabGTPase-activating proteins (RabGAPs) TBC1D1 and TBC1D4 play a crucial role in the regulation of GLUT4 translocation in response to insulin and contraction in skeletal muscle. In mice, deficiency in one or both RabGAPs leads to reduced insulin and contraction-stimulated glucose uptake, and to elevated fatty acid uptake and oxidation in both glycolytic and oxidative muscle fibers without altering mitochondrial copy number and the abundance of OXPHOS proteins. Here we present evidence for a novel mechanism of skeletal muscle lipid utilization involving the two RabGAPs and the fatty acid transporter SLC27A4/FATP4. Both RabGAPs control the uptake of saturated and unsaturated long-chain fatty acids (LCFAs) into skeletal muscle and knockdown of a subset of RabGAP substrates, <i>Rab8, Rab10 </i>or <i>Rab14, </i>decreased LCFA uptake into these cells. In skeletal muscle from <i>Tbc1d1/Tbc1d4</i> knockout animals, SLC27A4/FATP4 abundance was increased and depletion of SLC27A4/FATP4 but not FAT/CD36 completely abrogated the enhanced fatty acid oxidation in RabGAP-deficient skeletal muscle and cultivated C2C12 myotubes. Collectively, our data demonstrate that RabGAP-mediated control of skeletal muscle lipid metabolism converges with glucose metabolism at the level of downstream RabGTPases and involves regulated transport of LCFAs via SLC27A4/FATP4.


Author(s):  
Livia Belcastro ◽  
Carolina S. Ferreira ◽  
Marcelle A. Saraiva ◽  
Daniela B. Mucci ◽  
Antonio Murgia ◽  
...  

The rise in prevalence of obesity in women of reproductive age in both developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health, contributing to substantial economic burden on society. Placental lipid metabolism might be disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism and handling from women with pre-gestational obesity as a sole pregnancy complication and compared to placental responses of lean women. Open profile and targeted lipidomics were used to assess placental lipids and oxidized products of docosahexahenoic acid (DHA), neuroprostanes, and arachidonic acid (AA), isoprostanes. Placental fatty acid transporters FABP1, FABP3 and endothelial lipase protein were measured. Despite no signs of overall alterations in lipid content, increased contents of DHA, AA, DHA-derived neuroprostanes and AA-derived isoprostanes and decreased content of FABP1 protein were found in placentas from obese women. Multivariate analyses suggested that these oxidised fatty acids are associated with maternal and placental inflammation and also with birth weight. These results might shed light on the molecular mechanisms associated with altered fatty acid metabolism and lipid handling in maternal pre-gestational obesity, placing these oxidized fatty acids as novel mediators of placental function.


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