| 1. |
- Samad, Manisha, 1995, et al.
(författare)
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Elevated circulating adiponectin levels do not prevent anxiety-like behavior in a PCOS-like mouse model
- 2024
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Polycystic ovary syndrome (PCOS) is associated with symptoms of moderate to severe anxiety and depression. Hyperandrogenism is a key feature together with lower levels of the adipocyte hormone adiponectin. Androgen exposure leads to anxiety-like behavior in female offspring while adiponectin is reported to be anxiolytic. Here we test the hypothesis that elevated adiponectin levels protect against the development of androgen-induced anxiety-like behavior. Pregnant mice overexpressing adiponectin (APNtg) and wildtypes were injected with vehicle or dihydrotestosterone to induce prenatal androgenization (PNA) in the offspring. Metabolic profiling and behavioral tests were performed in 4-month-old female offspring. PNA offspring spent more time in the closed arms of the elevated plus maze, indicating anxiety-like behavior. Intriguingly, neither maternal nor offspring adiponectin overexpression prevented an anxiety-like behavior in PNA-exposed offspring. However, adiponectin overexpression in dams had metabolic imprinting effects, shown as lower fat mass and glucose levels in their offspring. While serum adiponectin levels were elevated in APNtg mice, cerebrospinal fluid levels were similar between genotypes. Adiponectin overexpression improved metabolic functions but did not elicit anxiolytic effects in PNA-exposed offspring. These observations might be attributed to increased circulating but unchanged cerebrospinal fluid adiponectin levels in APNtg mice. Thus, increased adiponectin levels in the brain are likely needed to stimulate anxiolytic effects.
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| 2. |
- Benrick, Anna, 1979, et al.
(författare)
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Adiponectin protects against development of metabolic disturbances in a PCOS mouse model
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:34
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Tidskriftsartikel (refereegranskat)abstract
- Adiponectin, together with adipocyte size, is the strongest factor associated with insulin resistance in women with polycystic ovary syndrome (PCOS). This study investigates the causal relationship between adiponectin levels and metabolic and reproductive functions in PCOS. Prepubertal mice overexpressing adiponectin from adipose tissue (APNtg), adiponectin knockouts (APNko), and their wild-type (WT) littermate mice were continuously exposed to placebo or dihydrotestosterone (DHT) to induce PCOS-like traits. As expected, DHT exposure led to reproductive dysfunction, as judged by continuous anestrus, smaller ovaries with a decreased number of corpus luteum, and an increased number of cystic/atretic follicles. A two-way between-groups analysis showed that there was a significant main effect for DHT exposure, but not for genotype, indicating adiponectin does not influence follicle development. Adiponectin had, however, some protective effects on ovarian function. Similar to in many women with PCOS, DHT exposure led to reduced adiponectin levels, larger adipocyte size, and reduced insulin sensitivity in WTs. APNtg mice remained metabolically healthy despite DHT exposure, while APNko-DHT mice were even more insulin resistant than their DHT-exposed littermate WTs. DHT exposure also reduced the mRNA expression of genes involved in metabolic pathways in gonadal adipose tissue of WT and APNko, but this effect of DHT was not observed in APNtg mice. Moreover, APNtg-DHT mice displayed increased pancreatic mRNA levels of insulin receptors, Pdx1 and Igf1R, suggesting adiponectin stimulates beta cell viability/hyperplasia in the context of PCOS. In conclusion, adiponectin improves metabolic health but has only minor effects on reproductive functions in this PCOS-like mouse model.
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| 3. |
- Johansson, Julia, 1982, et al.
(författare)
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Intense electroacupuncture normalizes insulin sensitivity, increases muscle GLUT4 content, and improves lipid profile in a rat model of polycystic ovary syndrome.
- 2010
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 299:4
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Tidskriftsartikel (refereegranskat)abstract
- Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and insulin resistance, possibly reflecting defects in skeletal muscle and adipocyte insulin signaling. Low-frequency (2 Hz) electroacupuncture (EA) increases insulin sensitivity in female rats with dihydrotestosterone (DHT)-induced PCOS, but the mechanism is unclear. We hypothesized that low-frequency EA regulates mediators involved in skeletal muscle glucose uptake and metabolism and alters the lipid profile in rats with DHT-induced PCOS. To test this hypothesis, we implanted in prepubescent female rats 90-day continuous-release pellets containing DHT (PCOS). At 70 days of age, the rats were randomly subdivided into two groups: one received low-frequency EA (evoking muscle twitches) for 20-25 min five times/wk for 4-5 wk; the other did not. Controls were implanted with pellets containing vehicle only. All three groups were otherwise handled similarly. Lipid profile was measured in fasting blood samples. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp, soleus muscle protein expression of glucose transporter 4 (GLUT4), and phosphorylated and nonphosphorylated Akt, and Akt substrate of 160 kDa was determined by Western blot analysis and GLUT4 location by immunofluorescence staining. PCOS EA rats had normalized insulin sensitivity, lower levels of total high-density lipoprotein and low-density lipoprotein cholesterol, and increased expression of GLUT4 in different compartments of skeletal muscle compared with PCOS rats. Total weight and body composition did not differ in the groups. Thus, in rats with DHT-induced PCOS, low-frequency EA has systemic and local effects involving intracellular signaling pathways in muscle that may, at least in part, account for the marked improved insulin sensitivity.
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| 4. |
- Stener-Victorin, Elisabet, 1964, et al.
(författare)
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Effects and mechanisms of acupuncture in the reproductive system.
- 2010
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Ingår i: Autonomic neuroscience : basic & clinical. - : Elsevier BV. - 1872-7484. ; 157:1-2, s. 46-51
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Tidskriftsartikel (refereegranskat)abstract
- The use of acupuncture to treat reproductive dysfunction has not been well investigated. Only a few clinical studies have been reported, most of which are flawed by poor design and a lack of valid outcome measures and diagnostic criteria, making the results difficult to interpret. Experimental studies, however, show that acupuncture has substantial effects on reproductive function. Here we review the possible mechanisms of action of acupuncture on the reproductive system and its effects on reproductive dysfunction, focusing in particular on polycystic ovary syndrome, the most common endocrine and metabolic disorder in women. Clinical and experimental evidence demonstrates that acupuncture is a suitable alternative or complement to pharmacological induction of ovulation, without adverse side effects. Clearly, acupuncture modulates endogenous regulatory systems, including the sympathetic nervous system, the endocrine system, and the neuroendocrine system. Randomized clinical trials are warranted to further evaluate the clinical effects of acupuncture in reproductive disorders.
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| 5. |
- Stener-Victorin, Elisabet, 1964, et al.
(författare)
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Effects of acupuncture and exercise on insulin sensitivity, adipose tissue characteristics, and markers of coagulation and fibrinolysis in women with polycystic ovary syndrome: secondary analyses of a randomized controlled trial.
- 2012
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 97:2, s. 501-508
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the possible effects of low-frequency electro-acupuncture (EA) and physical exercise on markers of coagulation and fibrinolysis, insulin sensitivity, and adipose tissue characteristics in women with PCOS. Design: Secondary analyses of a prospective, randomized controlled clinical trial. ClinicalTrials.gov (identifier NCT00484705) Settings: Department of Physiology and Department of Obstetrics and Gynecology, Universtiy of Gothenburg. Patients/Interventions: Eighty-four women with PCOS were randomized to sixteen weeks of low-frequency EA (14 treatments), physical exercise (at least 3 times/week) or no intervention. Main outcome measures: Anthropometrics, circulating coagulation and fibrinolytic markers, insulin sensitivity (euglycemic hyperinsulinemic clamp), hemodynamics, and adipose tissue morphology/function recorded at baseline, after 16 weeks of intervention, and after a 16 week follow-up. Results: In the low-frequency EA group, circulating plasminogen activator inhibitor (PAI-1) activity decreased by 21.8% after 16 weeks of intervention and by 31.1% at the 16 week follow-up and differed from the physical exercise and the no-intervention groups. The EA group had decreases in circulating fibrinogen and t-PA, sagittal diameter, and diastolic blood pressure after treatment, and fibrinogen remained lower at the 16-week follow-up. In the physical exercise group, lipoprotein lipase activity increased and diastolic blood pressure decreased after treatment, and both diastolic and systolic blood pressure were lower at follow-up. No other variables were affected. Conclusions: Low-frequency EA counteracted a possible prothrombotic state in women with PCOS, as reflected by a decrease in PAI-1 activity. Despite within-group improvements, there were no between-group differences in anthropometric, metabolic, or hemodynamic variables after 16 weeks of EA or physical exercise at the dose/intensity studied.
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| 6. |
- Mansor, Fazliana, et al.
(författare)
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Labisia pumila Upregulates Peroxisome Proliferator-Activated Receptor Gamma Expression in Rat Adipose Tissues and 3T3-L1 Adipocytes.
- 2013
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Ingår i: Advances in Pharmacological Sciences. - : Hindawi Limited. - 1687-6334 .- 1687-6342. ; :Article ID 808914
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Tidskriftsartikel (refereegranskat)abstract
- Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor that regulates lipid and glucose metabolism. We investigated the effects of Labisia pumila (LP) standardized water extract on PPARgamma transcriptional activity in adipocytes in vitro and in vivo. We used a rat model of dihydrotestosterone- (DHT-) induced polycystic ovary syndrome (PCOS), a condition characterized by insulin resistance. At 9 weeks of age, the PCOS rats were randomly subdivided into two groups: PCOS-LP (50mg/kg/day of LP) and PCOS-control (1mL of deionised water) for 4-5 weeks on the same schedule. Real-time RT-PCR was performed to determine the PPARgamma mRNA levels. LP upregulated PPARgamma mRNA level by 40% in the PCOS rats. Western blot analysis further demonstrated the increased PPARgamma protein levels in parallel with upregulation in mRNA. These observations were further proven by adipocytes culture. Differentiated 3T3-L1 adipocytes were treated with final concentration of 100 μ g/mL LP and compared to untreated control and 10 μ M of rosiglitazone (in type of thiazolidinediones). LP increased PPARgamma expressions at both mRNA and protein levels and enhanced the effect of glucose uptake in the insulin-resistant cells. The data suggest that LP may ameliorate insulin resistance in adipocytes via the upregulation of PPARgamma pathway.
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| 7. |
- Feng, Y., et al.
(författare)
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Acupuncture in polycystic ovary syndrome: Potential and challenge
- 2013
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Ingår i: Current Research in Acupuncture. - New York, NY : Springer New York. - 9781461433576 ; , s. 487-515
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Bokkapitel (refereegranskat)abstract
- Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder affecting 5-10 % of women of reproductive age. Conventional pharmacological therapy and surgery are effective but with obvious side effects and limited long-term treatment. Therefore, acupuncture therapy, as a complement or alternative to conventional therapies, may be an alternative for women with PCOS by reducing their symptoms. Experimental, mechanistic trials clearly indicate positive effects of acupuncture on reproductive and metabolic function. However, lack of randomized controlled trials hinders the translation and application of acupuncture in the treatment of PCOS. In this chapter, we summarize the PCOS diagnostic criteria and characters, PCOS-like animal models as well as the possible physiological basis and mechanism of the effect of acupuncture in PCOS. Clinical data from studies in women with PCOS and experimental observations in PCOS-like rat models suggest that acupuncture exerts long-lasting beneficial effects on metabolic, endocrine, and neuroendocrine systems. © 2013 Springer Science+Business Media New York. All rights are reserved.
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| 8. |
- Jedel, Elizabeth, 1962, et al.
(författare)
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Anxiety and depression symptoms in women with polycystic ovary syndrome compared with controls matched for body mass index.
- 2010
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Ingår i: Human reproduction. - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 25:2, s. 450-456
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Anxiety and depression are more prevalent in women with polycystic ovary syndrome (PCOS) than in those without this disorder. Possible confounding effects of overweight and obesity are suggested. The aim was to compare symptoms of anxiety and depression in women with PCOS and controls matched for age, body weight and body mass index (BMI). METHODS Women with PCOS (n = 30) and controls (n = 30) were recruited from the community. Persons with ongoing psychotropic medication were excluded. All potential participants underwent gynecological examination to confirm case-control status. Participants completed the self-reported versions of the Brief Scale for Anxiety (BSA-S) and Montgomery Asberg Depression Rating Scale (MADRS-S). RESULTS Women with PCOS had a higher BSA-S score compared with controls (median, range: 10.5, 1-24 versus 5.0, 0-28, P < 0.001). They scored higher on the following four individual symptoms: reduced sleep (2.0, 0-5 versus 0, 0-2, P < 0.001), worry (1.5, 0-4 versus 0, 0-6, P = 0.004), phobias (1, 0-4 versus 0, 0-3, P < 0.001), and pain (1, 0-3 versus 0, 0-2, P < 0.001). No statistical difference was demonstrated regarding MADRS-S scores (10.0, 0-27 versus 5.5, 0-24, P = 0.053). Only one of the nine MADRS-S symptoms, reduced sleep, which is also included in the BSA-S, differed between cases and controls. CONCLUSIONS Several anxiety symptoms distinguished women with PCOS from a control group matched on BMI. A better understanding of the symptoms is needed to identify and alleviate anxiety symptoms in this vulnerable group.
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| 9. |
- Mannerås Holm, Louise, 1980, et al.
(författare)
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Coagulation and Fibrinolytic Disturbances in Women with Polycystic Ovary Syndrome.
- 2011
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 96:4, s. 1068-76
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Tidskriftsartikel (refereegranskat)abstract
- Context: Studies of fibrinolysis/coagulation status in women with polycystic ovary syndrome (PCOS) are contradictory. Objectives: The aim of the study was to investigate whether women with PCOS have disturbed circulating levels of fibrinolysis/coagulation markers and, if so, whether the disturbances are related to hemodynamics, metabolic variables, sex steroids, SHBG, lipids, and inflammatory variables in women with PCOS. Design/Main Outcome Measures: Anthropometric variables, hemodynamics, circulating hemostatic and inflammatory markers, and serum lipid profile were measured in women with untreated PCOS (n = 74) and controls (n = 31). Results: After adjustments for age and body mass index (BMI), circulating plasminogen activator inhibitor 1 (PAI-1) activity and fibrinogen levels were higher in women with PCOS than controls; lipid profile, blood pressure, and levels of D-dimer, von Willebrand factor, factor VIII, tissue plasminogen activator, and inflammatory markers were comparable in the two groups. In multiple linear regression analyses including women with PCOS, low SHBG and high insulin predicted high PAI-1 activity (R(2) = 0.526; P < 0.001); elevated high-sensitivity C-reactive protein and soluble E-selectin in combination with heart rate predicted high fibrinogen (R(2) = 0.333; P < 0.001). Differences in PAI-1 activity were not significant after adjustments for age, BMI, SHBG, and insulin. Conclusions: PCOS is characterized by a prothrombotic state, as reflected by increased PAI-1 activity and fibrinogen, without signs of dyslipidemia or a proinflammatory state. Low SHBG and high insulin may partly explain the BMI-independent difference in PAI-1 activity between women with PCOS and controls. High-sensitivity C-reactive protein and E-selectin may be involved in regulating fibrinogen in PCOS.
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| 10. |
- Mannerås, Louise, 1980, et al.
(författare)
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A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome.
- 2007
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 148:8, s. 3781-91
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Tidskriftsartikel (refereegranskat)abstract
- Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity, and insulin resistance. However, its etiology is unclear, and its management is often unsatisfactory or requires a diversified approach. Here, we describe a new rat PCOS model, the first to exhibit both ovarian and metabolic characteristics of the syndrome. Female rats received the nonaromatizable androgen dihydrotestosterone (DHT) or the aromatase inhibitor letrozole by continuous administration, beginning before puberty, to activate androgen receptors. Adult DHT rats had irregular cycles, polycystic ovaries characterized by cysts formed from atretic follicles, and a diminished granulosa layer. They also displayed metabolic features, including increased body weight, increased body fat, and enlarged mesenteric adipocytes, as well as elevated leptin levels and insulin resistance. All letrozole rats were anovulatory and developed polycystic ovaries with structural changes strikingly similar to those in human PCOS. Our findings suggest that the formation of a "hyperplastic" theca interna reflects the inclusion of luteinized granulosa cells in the cyst wall rather than true hyperplasia. We conclude that the letrozole model is suitable for studies of the ovarian features of human PCOS, while the DHT model is suitable for studies of both ovarian and metabolic features of the syndrome.
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