GPR120 agonist ameliorated insulin resistance and improved ovarian function

Zygote ◽  
2021 ◽  
pp. 1-6
Author(s):  
Yang Liu ◽  
Jiayi Ding ◽  
Xiaofang Tan ◽  
Ya Shen ◽  
Li Xu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Rat Model ◽  
Lipid Accumulation ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Vital Role ◽  
Expression Levels ◽  
Glucose And Lipid Metabolism

Summary GPR120 is implicated in the regulation of glucose and lipid metabolism, and insulin resistance. In the current study, we aimed to investigate the role of GPR120 in polycystic ovary syndrome (PCOS). With the adoption of dehydroepiandrosterone, a rat model was established to simulate PCOS in vitro. mRNA and protein expression levels of GPR120 were measured using RT-qPCR and western blot, respectively. In addition, expression levels of testosterone, estradiol, luteinizing hormone and follicle-stimulating hormone, serum total cholesterol and triglyceride were assessed using the corresponding kits. Moreover, haematoxylin and eosin staining was used to detect pathological changes in ovary or liver and oil red staining was utilized to evaluate lipid accumulation. In the present study, GPR120 was downregulated in plasma, liver and ovary in the PCOS rat model. In addition, the GPR120 agonist regulated lipid metabolism in the liver and weight in the PCOS rat model. Furthermore, the GPR120 agonist decreased insulin resistance in the PCOS rat model but improved the ovarian function. It is suggested that GPR120 plays a vital role in suppressing insulin resistance, regulating ovary function and decreasing lipid accumulation in the liver, demonstrating that targeting GPR120 could be an effective method for the improvement of PCOS.

Melatonin ameliorates ovarian dysfunction by regulating autophagy in PCOS via the PI3K-Akt pathway

Reproduction ◽  
2021 ◽  
Author(s):  
Fenfen Xie ◽  
Junhui Zhang ◽  
Muxin Zhai ◽  
Yajing Liu ◽  
Hui Hu ◽  
...  
Keyword(s):  
Rat Model ◽  
Follicular Fluid ◽  
Molecular Mechanisms ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Akt Pathway ◽  
Therapeutic Drug ◽  
Ovarian Dysfunction ◽  
Protective Function ◽  
Expression Levels

Emerging evidence has demonstrated that melatonin (MT) plays a crucial role in regulating mammalian reproductive functions. It has been reported that MT has a protective effect on polycystic ovary syndrome (PCOS). However, the protective mechanisms of MT remain poorly understood. This study aims to explore the effect of MT on ovarian function in PCOS and to elucidate the relevant molecular mechanisms in vivo and in vitro. Here, we first analysed MT expression levels in the follicular fluid of PCOS patients. A significant reduction in MT expression levels was noted in PCOS patients. Intriguingly, reduced MT levels correlated with serum testosterone and inflammatory cytokine levels in follicular fluid. Moreover, we confirmed the protective function of MT through regulating autophagy in a dehydroepiandrosterone (DHEA)-induced PCOS rat model. Autophagy was activated in the ovarian tissue of the PCOS rat model, whereas additional MT inhibited autophagy by increasing PI3K-Akt pathway expression. In addition, serum-free testosterone, inflammatory and apoptosis indexes were reduced after MT supplementation. Furthermore, we also found that MT suppressed autophagy and apoptosis by activating the PI3K-Akt pathway in the DHEA-exposed human granulosa cell line KGN. Our study showed that MT ameliorated ovarian dysfunction by regulating autophagy in DHEA-induced PCOS via the PI3K-Akt pathway, revealing a potential therapeutic drug target for PCOS.

scholarly journals Nootkatone, a Dietary Fragrant Bioactive Compound, Attenuates Dyslipidemia and Intramyocardial Lipid Accumulation and Favorably Alters Lipid Metabolism in a Rat Model of Myocardial Injury: An In Vivo and In Vitro Study

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5656
Author(s):  
M.F. Nagoor Meeran ◽  
Sheikh Azimullah ◽  
M Marzouq Al Ahbabi ◽  
Niraj Kumar Jha ◽  
Vinoth-Kumar Lakshmanan ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Rat Model ◽  
Lipid Accumulation ◽  
Heart Diseases ◽  
Radical Scavenging ◽  
Enzymatic Antioxidants ◽  
Protective Effects ◽  
Altered Lipid Metabolism ◽  
Altered Lipid

In the present study, we assessed whether nootkatone (NKT), a sesquiterpene in edible plants, can provide protection against dyslipidemia, intramyocardial lipid accumulation, and altered lipid metabolism in a rat model of myocardial infarction (MI) induced by subcutaneous injections of isoproterenol (ISO, 85 mg/kg) on days 9 and 10. The rats were pre- and co-treated with NKT (10 mg/kg, p.o.) administered daily for 11 days. A significant reduction in the activities of myocardial creatine kinase and lactate dehydrogenase, as well as non-enzymatic antioxidants, and alterations in lipids and lipoproteins, along with a rise in plasma lipid peroxidation and intramyocardial lipid accumulation, were observed in ISO-treated rats. ISO administration induced alterations in the activities of enzymes/expressions that played a significant role in altering lipid metabolism. However, NKT treatment favorably modulated all biochemical and molecular parameters altered by ISO and showed protective effects against oxidative stress, dyslipidemia, and altered lipid metabolism, attributed to its free-radical-scavenging and antihyperlipidemic activities in rats with ISO-induced MI. Additionally, NKT decreased the accumulation of lipids in the myocardium as evidenced from Oil red O staining. Furthermore, the in vitro observations demonstrate the potent antioxidant property of NKT. The present study findings are suggestive of the protective effects of NKT on dyslipidemia and the underlying mechanisms. Based on our findings, it can be suggested that NKT or plants rich in NKT can be promising for use as a phytopharmaceutical or nutraceutical in protecting the heart and correcting lipid abnormalities and dyslipidemia, which are risk factors for ischemic heart diseases.

scholarly journals Metabolism and Ovarian Function in PCOS Women: A Therapeutic Approach with Inositols

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Antonio Simone Laganà ◽  
Paola Rossetti ◽  
Massimo Buscema ◽  
Sandro La Vignera ◽  
Rosita Angela Condorelli ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Second Messengers ◽  
Biological Functions ◽  
Androgen Excess ◽  
Glucose And Lipid Metabolism ◽  
Insulin Sensitizers ◽  
Degree Of Severity ◽  
Correlate Data

Polycystic ovary syndrome (PCOS) is characterized by chronical anovulation and hyperandrogenism which may be present in a different degree of severity. Insulin-resistance and hyperinsulinemia are the main physiopathological basis of this syndrome and the failure of inositol-mediated signaling may concur to them. Myo (MI) and D-chiro-inositol (DCI), the most studied inositol isoforms, are classified as insulin sensitizers. In form of glycans, DCI-phosphoglycan and MI-phosphoglycan control key enzymes were involved in glucose and lipid metabolism. In form of phosphoinositides, they play an important role as second messengers in several cellular biological functions. Considering the key role played by insulin-resistance and androgen excess in PCOS patients, the insulin-sensitizing effects of both MI and DCI were tested in order to ameliorate symptoms and signs of this syndrome, including the possibility to restore patients’ fertility. Accumulating evidence suggests that both isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS, although MI showed the most marked effect on the metabolic profile, whereas DCI reduced hyperandrogenism better. The purpose of this review is to provide an update on inositol signaling and correlate data on biological functions of these multifaceted molecules, in view of a rational use for the therapy in women with PCOS.

scholarly journals Ketogenic Diets Induced Glucose Intolerance and Lipid Accumulation in Mice with Alterations in Gut Microbiota and Metabolites

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Yue Li ◽  
Xin Yang ◽  
Jing Zhang ◽  
Tianyi Jiang ◽  
Ziyi Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Neurodegenerative Diseases ◽  
Ketogenic Diet ◽  
Glucose Intolerance ◽  
Lipid Accumulation ◽  
Fat Accumulation ◽  
Glucose And Lipid Metabolism ◽  
Ketogenic Diets

ABSTRACT The ketogenic diet (KD), which can induce changes in gut microbiota, has shown benefits for epilepsy and several neurodegenerative diseases. However, the effects of a KD on glucose and lipid metabolism remain inconclusive. Using two formulas of ketogenic diets (KDR with 89.5% fat and KDH with 91.3% fat), which are commonly used in mouse trials, we found that KDR but not KDH induced insulin resistance and damaged glucose homeostasis, while KDH induced more fat accumulation in mice. Further study showed that KD impacted glucose metabolism, which was related to the sources of fat, while both the sources and proportions of fat affected lipid metabolism. And the KD widely used in human studies still induced insulin resistance and fat accumulation in mice. Moreover, KDs changed the gut microbiota and metabolites in mice, and the sources and proportions of fat in the diets respectively changed the abundance of specific bacteria and metabolites which were correlated with parameters related to glucose intolerance and lipid accumulation. Overall, our study demonstrated that the metabolic disorders induced by KDs are closely related to the source and proportion of fat in the diet, which may be associated with the changes of the gut microbiota and metabolites. IMPORTANCE The ketogenic diet with extremely high fat and very low carbohydrate levels is very popular in society today. Although it has beneficial effects on epilepsy and neurodegenerative diseases, how ketogenic diets impact host glucose and lipid metabolism and gut microbiota still needs further investigation. Here, we surveyed the effects of two ketogenic diets which are commonly used in mouse trials on metabolic phenotypes, gut microbiota, and metabolites in mice. We found that both ketogenic diets impaired glucose and lipid metabolism in mice, and this may be due to the sources and proportions of fat in the diets. This work highlights the potential risk of glucose and lipid metabolism disorders and the importance of evaluating the sources and proportions of fat in the diets, when using ketogenic diets for weight loss and the treatment of diseases.

scholarly journals A Dietary Medium-Chain Fatty Acid, Decanoic Acid, Inhibits Recruitment of Nur77 to the HSD3B2 Promoter In Vitro and Reverses Endocrine and Metabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 382-394 ◽  
Author(s):  
Bao Hui Lee ◽  
Inthrani Raja Indran ◽  
Huey Min Tan ◽  
Yu Li ◽  
Zhiwei Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Polycystic Ovary Syndrome ◽  
Rat Model ◽  
Polycystic Ovary ◽  
Decanoic Acid ◽  
Chain Fatty Acid ◽  
Metabolic Abnormalities ◽  
Ovary Syndrome

Abstract Hyperandrogenism is the central feature of polycystic ovary syndrome (PCOS). Due to the intricate relationship between hyperandrogenism and insulin resistance in PCOS, 50%–70% of these patients also present with hyperinsulinemia. Metformin, an insulin sensitizer, has been used to reduce insulin resistance and improve fertility in women with PCOS. In previous work, we have noted that a dietary medium-chain fatty acid, decanoic acid (DA), improves glucose tolerance and lipid profile in a mouse model of diabetes. Here, we report for the first time that DA, like metformin, inhibits androgen biosynthesis in NCI-H295R steroidogenic cells by regulating the enzyme 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase type 2 (HSD3B2). The inhibitory effect on HSD3B2 and androgen production required cAMP stimulation, suggesting a mechanistic action via the cAMP-stimulated pathway. Specifically, both DA and metformin reduced cAMP-enhanced recruitment of the orphan nuclear receptor Nur77 to the HSD3B2 promoter, coupled with decreased transcription and protein expression of HSD3B2. In a letrozole-induced PCOS rat model, treatment with DA or metformin reduced serum-free testosterone, lowered fasting insulin, and restored estrous cyclicity. In addition, DA treatment lowered serum total testosterone and decreased HSD3B2 protein expression in the adrenals and ovaries. We conclude that DA inhibits androgen biosynthesis via mechanisms resulting in the suppression of HSD3B2 expression, an effect consistently observed both in vitro and in vivo. The efficacy of DA in reversing the endocrine and metabolic abnormalities of the letrozole-induced PCOS rat model are promising, raising the possibility that diets including DA could be beneficial for the management of both hyperandrogenism and insulin resistance in PCOS.

scholarly journals Schistosoma japonicum Infection Leads to the Reprogramming of Glucose and Lipid Metabolism in the Colon of Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaoying Yang ◽  
Weimin Ding ◽  
Xinyu Qian ◽  
Pengfei Jiang ◽  
Qingqing Chen ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Schistosoma Japonicum ◽  
Underlying Mechanism ◽  
Vital Role ◽  
Metabolic Reprogramming ◽  
Downstream Signaling ◽  
Tensin Homolog ◽  
Glucose And Lipid Metabolism

The deposition of Schistosoma japonicum (S. japonicum) eggs commonly induces inflammation, fibrosis, hyperplasia, ulceration, and polyposis in the colon, which poses a serious threat to human health. However, the underlying mechanism is largely neglected. Recently, the disorder of glucose and lipid metabolism was reported to participate in the liver fibrosis induced by the parasite, which provides a novel clue for studying the underlying mechanism of the intestinal pathology of the disease. This study focused on the metabolic reprogramming profiles of glucose and lipid in the colon of mice infected by S. japonicum. We found that S. japonicum infection shortened the colonic length, impaired intestinal integrity, induced egg-granuloma formation, and increased colonic inflammation. The expression of key enzymes involved in the pathways regulating glucose and lipid metabolism was upregulated in the colon of infected mice. Conversely, phosphatase and tensin homolog deleted on chromosome ten (PTEN) and its downstream signaling targets were significantly inhibited after infection. In line with these results, in vitro stimulation with soluble egg antigens (SEA) downregulated the expression of PTEN in CT-26 cells and induced metabolic alterations similar to that observed under in vivo results. Moreover, PTEN over-expression prevented the reprogramming of glucose and lipid metabolism induced by SEA in CT-26 cells. Overall, the present study showed that S. japonicum infection induces the reprogramming of glucose and lipid metabolism in the colon of mice, and PTEN may play a vital role in mediating this metabolic reprogramming. These findings provide a novel insight into the pathogenicity of S. japonicum in hosts.

scholarly journals Ketogenic diets induced glucose intolerance and lipid accumulation in mice with alterations in gut microbiota and metabolites

2020 ◽  
Author(s):  
Yue Li ◽  
Xin Yang ◽  
Jing Zhang ◽  
Tianyi Jiang ◽  
Ziyi Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Ketogenic Diet ◽  
Glucose Intolerance ◽  
Lipid Accumulation ◽  
Fat Accumulation ◽  
Glucose And Lipid Metabolism ◽  
Ketogenic Diets ◽  
Tryptophan Metabolites

Abstract Background: A ketogenic diet (KD), which is extremely high in fat with a very low carbohydrate level and can induce changes in gut microbiota, has shown benefits for epilepsy and several neurodegenerative diseases. However, the effects of a KD on glucose and lipid metabolism remain inconclusive.Results: Using two formulas of ketogenic diets (KDR with 89.5% fat and KDH with 91.3% fat), which are commonly used in mouse trials, we found that KDR but not KDH induced insulin resistance and damaged glucose homeostasis, while KDH induced more fat accumulation in mice. In addition to the differences in the proportions of nutrients between the two kinds of KD, we found that the sources of fat in KDR were mainly trans-fatty acids. Further study showed that KD impacted glucose metabolism, which was related to the sources of fat, while both the sources and proportions of fat affected lipid metabolism. We found that both the sources and proportions of fat changed the abundance of specific bacteria in Lachnospiraceae and Oscillibacter, which positively correlated with parameters related to lipid accumulation. The abundances of specific bacteria in Bacteroides and Ruminococcaceae were only affected by the sources of fat, and specific bacteria from Lactococcus and Roseburia were only affected by the proportions of fat. Moreover, alterations in the concentrations of SCFAs and tryptophan metabolites, which were negatively correlated with parameters related to lipid accumulation, were also affected by the sources of fat. In addition, the ketogenic diet widely used in human studies still induced insulin resistance and fat accumulation in mice; enhanced Roseburia, Ruminococcaceae and Lachnospiraceae; reduced Turicibacter; increased bile acids and decreased SCFAs.Conclusions: Overall, our study demonstrated that ketogenic diets induced glucose intolerance and lipid accumulation in mice, which is closely related to the source and proportion of fat in the diet, likely due to changes in the gut microbiota and metabolites.

Abstract P274: Fruit Extract (blueberry, Cranberry, And Promegranate) Improved Insulin Resistance In Overweight Hypertensive And Normotensive Subjects

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Ludmila N Novaes ◽  
Mariele Moraes ◽  
Keyla Katayama ◽  
Carine Sangaleti ◽  
Maria Claudia Irigoyen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Repeated Measures ◽  
Hdl Cholesterol ◽  
Biochemical Tests ◽  
Fruit Extract ◽  
Hypertensive Patients ◽  
Glucose And Lipid Metabolism ◽  
Normotensive Subjects ◽  
Group B

Arterial hypertension is frequently associated to glucose and lipid metabolism abnormalities. The purpose of this study was to determine if antioxidants (fruit extract) supplementation interfere with glucose and lipid metabolism in overweight hypertensive patients. A randomized clinical trial was conducted with 30 individuals, 23 hypertensive patients (group A) and 7 normotensive controls (group B). They were randomized to take 3 capsules of different fruits extract a day (blueberry, cranberry and pomegranate) or placebo for 4 weeks. This is a crossover study, which started with placebo changed to capsules and vice versa. Blood samples were collected after 12 hours fasting for biochemical tests (glucose, insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), anthropometric assessment (weight, height, and body mass index), systolic BP, diastolic BP and heart rate were evaluated at baseline, after 4, and 8 weeks. The comparisons between groups were held with the GLM repeated measures. Twenty three hypertensive patients (age 47 years, 14 females) and 7 normotensive controls (age 40 years, 7 females) were evaluated. BMI, blood pressure, heart and lipid profile did not differ between groups. HOMAir decreased significantly in both groups. See results in table 1. Values are expressed as medians (±SD) In these preliminary results a 4-weeks supplementation of antioxidants (fruit extract) improved insulin resistance in overweight hypertensive and normotensive subjects. Financial support: FAPESP 2014/25808-3

Improvement of glucose and lipid metabolism in diabetic rats treated with molybdate

1996 ◽  
Vol 270 (2) ◽  
pp. E344-E352 ◽  
Author(s):  
A. T. Ozcelikay ◽  
D. J. Becker ◽  
L. N. Ongemba ◽  
A. M. Pottier ◽  
J. C. Henquin ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fatty Acid Synthase ◽  
Diabetic Rats ◽  
Nonesterified Fatty Acids ◽  
Insulin Resistant ◽  
Hepatic Glucose Metabolism ◽  
Glucose And Lipid Metabolism ◽  
Glycogen Stores

Molybdenum mimics certain insulin actions in vitro. We have investigated the effects of oral administration of Na2MoO4 (Mo) for 8 wk on carbohydrate and lipid metabolism in streptozotocin-diabetic rats. Mo decreased hyperglycemia and glucosuria by 75% and corrected the elevation of plasma nonesterified fatty acids. Tolerance to glucose loads was improved, and glycogen stores were replenished. These effects were not due to a rise of insulinemia. In liver, Mo restored the blunted mRNA and activity of glucokinase and pyruvate kinase and decreased to normal phosphoenolpyruvate carboxykinase values. Finally, Mo totally reversed the low expression and activity of acetyl-CoA carboxylase and fatty acid synthase in liver, but not in white adipose tissue. In conclusion, Mo exerts a marked blood glucose-lowering effect in diabetic rats by an insulin-like action. This effect results in part from a restoration of hepatic glucose metabolism and is associated with a tissue-specific correction of lipogenic enzyme gene expression, both processes being essentially mediated by reversal of impaired pretranslational regulatory mechanisms. These observations raise new therapeutic perspectives in diabetes, particularly in the insulin-resistant condition.

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