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- Johansson, Julia, 1982, et al.
(författare)
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Electrical vs Manual Acupuncture Stimulation in a Rat Model of Polycystic Ovary Syndrome: Different Effects on Muscle and Fat Tissue Insulin Signaling
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- In rats with dihydrotestosterone (DHT)-induced polycystic ovary syndrome (PCOS), repeated low-frequency electrical stimulation of acupuncture needles restores whole-body insulin sensitivity measured by euglycemic hyperinsulinemic clamp. We hypothesized that electrical stimulation causing muscle contractions and manual stimulation causing needle sensation have different effects on insulin sensitivity and related signaling pathways in skeletal muscle and adipose tissue, with electrical stimulation being more effective in DHT-induced PCOS rats. From age 70 days, rats received manual or low-frequency electrical stimulation of needles in abdominal and hind limb muscle five times/wk for 4–5 wks; controls were handled but untreated rats. Low-frequency electrical stimulation modified gene expression (decreased Tbc1d1 in soleus, increased Nr4a3 in mesenteric fat) and protein expression (increased pAS160/AS160, Nr4a3 and decreased GLUT4) by western blot and increased GLUT4 expression by immunohistochemistry in soleus muscle; glucose clearance during oral glucose tolerance tests was unaffected. Manual stimulation led to faster glucose clearance and modified mainly gene expression in mesenteric adipose tissue (increased Nr4a3, Mapk3/Erk, Adcy3, Gsk3b), but not protein expression to the same extent; however, Nr4a3 was reduced in soleus muscle. The novel finding is that electrical and manual muscle stimulation affect glucose homeostasis in DHT-induced PCOS rats through different mechanisms. Repeated electrical stimulation regulated key functional molecular pathways important for insulin sensitivity in soleus muscle and mesenteric adipose tissue to a larger extent than manual stimulation. Manual stimulation improved whole-body glucose tolerance, an effect not observed after electrical stimulation, but did not affect molecular signaling pathways to the same extent as electrical stimulation. Although more functional signaling pathways related to insulin sensitivity were affected by electrical stimulation, our findings suggest that manual stimulation of acupuncture needles has a greater effect on glucose tolerance. The underlying mechanism of the differential effects of the intermittent manual and the continuous electrical stimulation remains to be elucidated.
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| 2. |
- Lager, Susanne, 1978, et al.
(författare)
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Effect of IL-6 and TNF-α on fatty acid uptake in cultured human primary trophoblast cells.
- 2011
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Ingår i: Placenta. - : Elsevier BV. - 1532-3102 .- 0143-4004. ; 32:2, s. 121-7
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Tidskriftsartikel (refereegranskat)abstract
- Maternal obesity and gestational diabetes (GDM) are conditions associated with fetal overgrowth and excessive fat accumulation in the fetus, implicating an increased placental nutrient transfer in these pregnancies. Obese and GDM mothers have altered metabolism and hormone levels, including elevation of maternal circulatory lipids and pro-inflammatory cytokines. We tested the hypothesis that interleukin (IL)-6 and tumor necrosis factor (TNF)-α stimulate placental fatty acid transport, as these pro-inflammatory cytokines have been shown to affect lipid metabolism in other tissues. In cultured primary human trophoblast cells IL-6, but not TNF-α, stimulated fatty acid accumulation, as measured by BODIPY fluorescence. The increased fatty acid accumulation could not be explained by an increased expression of key components in placental fatty acid transport, such as adipophilin, fatty acid transport protein (FATP)1, FATP4, or lipoprotein lipase. In a cohort of lean and overweight/obese pregnant women, increasing maternal third trimester IL-6 plasma concentrations correlated with decreasing placental lipoprotein lipase activity. However, as no effect on lipoprotein lipase activity was observed in cultured trophoblast cells after exposure to either IL-6 or TNF-α, the correlation between maternal circulatory IL-6 levels and placental lipoprotein lipase activity at term is unlikely to represent a cause-and-effect relationship. In conclusion, high levels of IL-6 stimulate trophoblast fatty acid accumulation, which could contribute to an excessive nutrient transfer in conditions associated with elevated maternal IL-6 such as obesity and gestational diabetes.
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| 6. |
- Magnusson-Olsson, AnneLiese, et al.
(författare)
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Effect of maternal triglycerides and free fatty acids on placental LPL in cultured primary trophoblast cells and in a case of maternal LPL deficiency.
- 2007
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Ingår i: Am J Physiol Endocrinol Metab. ; 293:1
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Tidskriftsartikel (refereegranskat)abstract
- Maternal hypertriglyceridemia is a normal condition in late gestation and is an adaptation to ensure an adequate nutrient supply to the fetus. Placental lipoprotein lipase (LPL) is involved in the initial step in transplacental fatty acid transport as it hydrolyzes maternal triglycerides (TG) to release free fatty acids (FFA). We investigated LPL activity and protein (Western blot) and mRNA expression (real-time RT-PCR) in the placenta of an LPL-deficient mother with marked hypertriglyceridemia. The LPL activity was fourfold lower, LPL protein expression 50% lower, and mRNA expression threefold higher than that of normal, healthy placentas at term (n = 4-7). To further investigate the role of maternal lipids in placental LPL regulation, we isolated placental cytotrophoblasts from term placentas and studied LPL activity and protein and mRNA expression after incubation in Intralipid (as a source of TG) and oleic, linoleic, and a combination of oleic, linoleic, and arachidonic acids as well as insulin. Intralipid (40 and 400 mg/dl) decreased LPL activity by approximately 30% (n = 10-14, P < 0.05) and 400 microM linoleic and linoleic-oleic-arachidonic acid (n = 10) decreased LPL activity by 37 and 34%, respectively. No major changes were observed in LPL protein or mRNA expression. We found no effect of insulin on LPL activity or protein expression in the cultured trophoblasts. To conclude, the activity of placental LPL is reduced by high levels of maternal TG and/or FFA. This regulatory mechanism may serve to counteract an excessive delivery of FFA to the fetus in conditions where maternal TG levels are markedly increased.
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| 7. |
- Magnusson-Olsson, AnneLiese, et al.
(författare)
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Gestational and hormonal regulation of human placental lipoprotein lipase
- 2006
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Ingår i: J Lipid Res. ; 47:11, s. 2551-61
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Tidskriftsartikel (refereegranskat)abstract
- The fetal demand for FFA increases as gestation proceeds, and LPL represents one potential mechanism for increasing placental lipid transport. We examined LPL activity and protein expression in first trimester and term human placenta. The LPL activity was 3-fold higher in term (n = 7; P < 0.05) compared with first trimester (n = 6) placentas. The LPL expression appeared lower in microvillous membrane from first trimester (n = 2) compared with term (n = 2) placentas. We incubated isolated placental villous fragments with a variety of effectors [GW 1929, estradiol, insulin, cortisol, epinephrine, insulin-like growth factor-1 (IGF-1), and tumor necrosis factor-alpha] for 1, 3, and 24 h to investigate potential regulatory mechanisms. Decreased LPL activity was observed after 24 h of incubation with estradiol (1 micro g/ml), insulin, cortisol, and IGF-1 (n = 12; P < 0.05). We observed an increase in LPL activity after 3 h of incubation with estradiol (20 ng/ml) or hyperglycemic medium plus insulin (n = 7; P < 0.05). To conclude, we suggest that the gestational increase in placental LPL activity represents an important mechanism to enhance placental FFA transport in late pregnancy. Hormonal regulation of placental LPL activity by insulin, cortisol, IGF-1, and estradiol may be involved in gestational changes and in alterations in LPL activity in pregnancies complicated by altered fetal growth.
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| 8. |
- Magnusson-Olsson, AnneLiese
(författare)
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Placental LPL and glucose metabolism in complicated pregnancies
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Pregnancies complicated by intrauterine growth restriction (IUGR) or diabetes are associated with alterations in both lipid and glucose metabolism, which may lead to long lasting metabolic disturbances in the fetus and susceptibility for developing metabolic syndrome in postnatal life. Glucose is the major energy source for both the fetus and placenta. Many fetuses suffering from IUGR are hypoglycaemic in utero and we speculated that the IUGR placenta consumes more glucose leaving less for transport to the fetus. The fetal lipid demand increases as gestation proceeds and lipids are used to build cell membranes and for brain development. An insufficient supply could lead to neurological or vascular complications. The IUGR and diabetic newborn have lower and higher fat depots, respectively. We speculated that the placental capacity for fatty acid transfer is altered in these pregnancy complications. Triglyceride hydrolases in the placental are critical in releasing fatty acids (FFA) from maternal lipoproteins, making FFA available for transport to the fetus. METHODS: We determined activity (spectrophotometric method) and protein expression (Western blot) of the glycolytic enzymes phosphofructo kinase (PFK), pyruvate kinase (PK) and hexokinase (HXK) in homogenates of IUGR and normal placentas. Glucose consumption and lactate production in fresh placental villous tissue using a perifusion system was measured. We also studied activity and expression of lipoprotein lipase (LPL) and placenta specific TG hydrolase in microvillous membrane (MVM) and expression of L-FABP and C-FABP in homogenates in placentas from IUGR and diabetic pregnancies. The TG hydrolase activities were assessed by measuring hydrolysis of 3H-Trioleic acid incorporated into Intralipid® micelles. We also investigated regulation of LPL in placental villous tissue (activity and protein expression) or isolated placental cytotrophoblasts (activity protein, and mRNA expression) in response to hormones, free fatty acids, triglycerides and glucose. We investigated LPL activity, protein and mRNA expression (real time RT PCR) in the placenta from a LPL deficient mother with marked hypertriglyceridemia.RESULTS: The activity of PFK was 32% lower in IUGR placentas (p<0.05). Placental glucose consumption in IUGR was not different from AGA whereas lactate production was decreased by 28 % in IUGR (p<0.05). LPL activity was reduced by 47% in preterm IUGR (p<0.05) whereas the LPL activity in IDDM pregnancies was increased by 39% (p<0.05) as compared to controls. The expression of L-FABP was increased by 112% in IDDM (p<0.05) and by 64% in GDM (p<0.05). The LPL activity was 3-fold higher in term as compared to first trimester placentas (p<0.05). No change was seen after incubation for 1 and 3 h but after 24 h incubation with estradiol, insulin, cortisol and IGF-1 LPL activity decreased (p<0.05). In further studies of LPL regulation, we observed an increase in LPL activity after 3 h incubation with physiological concentrations of estradiol (20 ng/ml) (p<0.05) and hyperglycemic media plus insulin (p<0.05). In the placenta from the LPL deficient mother LPL activity was four-fold lower as compared with normal placentas (p<0.05), the LPL protein expression 50% lower (p<0.05) and mRNA expression threefold higher (p<0.05) than that of normal term placentas. Intralipid (a source of triglycerides) (400 mg/dl) decreased LPL activity by 30% (p<0.05) and 400 µM oleic and linoleic acid decreased LPL activity by 62 and 52 %, respectively (p<0.05). CONCLUSIONS: The hypoglycemia in IUGR fetuses is not due to an increased placental glucose consumption but our data supports an altered glycolytic pathway in the IUGR placenta. The alterations demonstrated in MVM LPL activity and L-FABP expression in IUGR and diabetic placentas may contribute to the altered lipid deposition and metabolism in these pregnancies. We suggest that the gestational increase in placental LPL activity represents an important mechanism to enhance placental FFA transport in late pregnancy and that hormonal and lipid regulation of placental LPL activity by insulin, cortisol, IGF-1, estradiol, FFAs and triglycerides may be involved in gestational changes and in alterations in LPL activity in pregnancies complicated by altered fetal growth.
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