scholarly journals Exercise-Induced Irisin, the Fat Browning Myokine, as a Potential Anticancer Agent

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
George-Emmanuel Maalouf ◽  
Diala El Khoury
Keyword(s):  
Insulin Resistance ◽  
Anticancer Agent ◽  
Metabolic Diseases ◽  
Fat Metabolism ◽  
Positive Effects ◽  
Different Types ◽  
Negative Effect ◽  
Exercise Induced

Irisin is a recently discovered myokine that plays an important role in fat metabolism through the browning of white adipose tissue. This myokine is usually secreted after exercise by improving energy balance and has shown great potential as a possible treatment for some metabolic diseases such as obesity, insulin resistance, and inflammation. Obesity has been linked to a higher incidence of some cancers. Furthermore, some studies have shown irisin to have direct positive effects on different types of cancers. Although it is hard to relay conclusions from in vitro to in vivo studies, the majority of the available data favor irisin as a potential substance for cancer regression through reducing proinflammatory markers linked to obesity. However, some controversies remain on the exact benefits of irisin on cancer with some studies showing no or even a negative effect of irisin on cancer. This review summarizes these 2 differing viewpoints and synthesizes them to form a clearer picture of exercise-induced irisin’s effects on cancer.

scholarly journals Exposure to the Widely Used Pyrethroid Pesticide Deltamethrin, Does Not Exacerbate High Fat Diet Induced Obesity or Insulin Resistance in C57BL/6J Mice

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A45-A46
Author(s):  
Evangelia Evelyn Tsakiridis ◽  
Marisa Morrow ◽  
Andrea Llanos ◽  
Bo Wang ◽  
Alison Holloway ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glycemic Control ◽  
Metabolic Diseases ◽  
Uncoupling Protein ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Pyrethroid Pesticide ◽  
First Time

Abstract Deltamethrin is a commonly used pesticide for the control of mosquito populations. Despite widespread use, the effects of deltamethrin on adiposity and glucose homeostasis have been equivocal with some studies showing increased, decreased and no effect on adiposity and glycemic control. However, no study to date has investigated the effect of deltamethrin in mice housed at thermoneutral temperatures, which is important for modelling metabolic diseases in rodents due to reduced thermal stress and constitutive activation of brown adipose tissue. In the current study we demonstrate for the first time that deltamethrin reduces uncoupling protein-1 expression in brown adipocytes cultured in vitro at concentrations as low as 1pm. Meanwhile, in-vivo deltamethrin does not appear to alter glycemic control or promote adiposity at exposures equivalent to 0.01, 0.1 or 1.0 mg/kg/day. Together, our study demonstrates environmentally relevant exposure to deltamethrin does not exacerbate diet induced obesity or insulin resistance.

scholarly journals Effects of Food Processing on In Vivo Antioxidant and Hepatoprotective Properties of Green Tea Extracts

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 572 ◽  
Author(s):  
Xiao-Yu Xu ◽  
Jie Zheng ◽  
Jin-Ming Meng ◽  
Ren-You Gan ◽  
Qian-Qian Mao ◽  
...  
Keyword(s):  
Green Tea ◽  
Food Processing ◽  
Antioxidant Activities ◽  
Ultrasound Treatment ◽  
Positive Effects ◽  
In Vivo Experiments ◽  
Study Results ◽  
Negative Effect

Food processing can affect the nutrition and safety of foods. A previous study showed that tannase and ultrasound treatment could significantly increase the antioxidant activities of green tea extracts according to in vitro evaluation methods. Since the results from in vitro and in vivo experiments may be inconsistent, the in vivo antioxidant activities of the extracts were studied using a mouse model of alcohol-induced acute liver injury in this study. Results showed that all the extracts decreased the levels of aspartate transaminase and alanine aminotransferase in serum, reduced the levels of malondialdehyde and triacylglycerol in the liver, and increased the levels of catalase and glutathione in the liver, which can alleviate hepatic oxidative injury. In addition, the differences between treated and original extracts were not significant in vivo. In some cases, the food processing can have a negative effect on in vivo antioxidant activities. That is, although tannase and ultrasound treatment can significantly increase the antioxidant activities of green tea extracts in vitro, it cannot improve the in vivo antioxidant activities, which indicates that some food processing might not always have positive effects on products for human benefits.

scholarly journals GRP75 Regulates Mitochondrial-Supercomplex Turnover to Modulate Insulin Sensitivity

2021 ◽  
Author(s):  
Qiongya Zhao ◽  
Ting Luo ◽  
Feng Gao ◽  
Yinxu Fu ◽  
Bin Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Metabolic Diseases ◽  
Chain Complex ◽  
Complex Activity ◽  
Insulin Resistant ◽  
Mitochondrial Homeostasis ◽  
Dna Release

GRP75, defined as a major component of both mitochondrial quality control system and mitochondria-associated membrane, plays a key role in mitochondrial homeostasis. In this study, we assessed the roles of GRP75, other than as a component, in insulin action in both<i> in vitro</i> and <i>in vivo</i> models with insulin resistance. We found that GRP75 was downregulated in HFD-fed mice, and induction of <i>Grp75</i> in mice could prevent HFD induced obesity and insulin resistance. Mechanistically, GRP75 influenced insulin sensitivity by regulating mitochondrial function through its modulation of mitochondrial-supercomplex turnover rather than MAM communication: GRP75 was negatively associated with respiratory-chain complex activity and was essential for mitochondrial-supercomplex assembly and stabilization. Moreover, mitochondrial dysfunction in <i>Grp75</i>-knockdown cells might further increase mitochondrial fragmentation, thus trigger cytosolic mitochondrial DNA release and activate the cGAS/STING-dependent pro-inflammatory response.<b> </b>Therefore, GRP75 can serve as a potential therapeutic target of insulin resistant-related diabetes or other metabolic diseases.

scholarly journals GRP75 Regulates Mitochondrial-Supercomplex Turnover to Modulate Insulin Sensitivity

2021 ◽  
Author(s):  
Qiongya Zhao ◽  
Ting Luo ◽  
Feng Gao ◽  
Yinxu Fu ◽  
Bin Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Metabolic Diseases ◽  
Chain Complex ◽  
Complex Activity ◽  
Insulin Resistant ◽  
Mitochondrial Homeostasis ◽  
Dna Release

GRP75, defined as a major component of both mitochondrial quality control system and mitochondria-associated membrane, plays a key role in mitochondrial homeostasis. In this study, we assessed the roles of GRP75, other than as a component, in insulin action in both<i> in vitro</i> and <i>in vivo</i> models with insulin resistance. We found that GRP75 was downregulated in HFD-fed mice, and induction of <i>Grp75</i> in mice could prevent HFD induced obesity and insulin resistance. Mechanistically, GRP75 influenced insulin sensitivity by regulating mitochondrial function through its modulation of mitochondrial-supercomplex turnover rather than MAM communication: GRP75 was negatively associated with respiratory-chain complex activity and was essential for mitochondrial-supercomplex assembly and stabilization. Moreover, mitochondrial dysfunction in <i>Grp75</i>-knockdown cells might further increase mitochondrial fragmentation, thus trigger cytosolic mitochondrial DNA release and activate the cGAS/STING-dependent pro-inflammatory response.<b> </b>Therefore, GRP75 can serve as a potential therapeutic target of insulin resistant-related diabetes or other metabolic diseases.

scholarly journals Low-dose naltrexone rescues inflammation and insulin resistance associated with hyperinsulinemia

2020 ◽  
Vol 295 (48) ◽  
pp. 16359-16369
Author(s):  
Abhinav Choubey ◽  
Khyati Girdhar ◽  
Aditya K. Kar ◽  
Shaivya Kushwaha ◽  
Manoj Kumar Yadav ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Inflammatory Mediators ◽  
Low Dose ◽  
Metabolic Diseases ◽  
Nuclear Translocation ◽  
Critical Role ◽  
Systemic Insulin Resistance ◽  
Low Dose Naltrexone

The incidence of diabetes, obesity, and metabolic diseases has reached an epidemic status worldwide. Insulin resistance is a common link in the development of these conditions, and hyperinsulinemia is a central hallmark of peripheral insulin resistance. However, how hyperinsulinemia leads to systemic insulin resistance is less clear. We now provide evidence that hyperinsulinemia promotes the release of soluble pro-inflammatory mediators from macrophages that lead to systemic insulin resistance. Our observations suggest that hyperinsulinemia induces sirtuin1 (SIRT1) repression and stimulates NF-κB p65 nuclear translocation and transactivation of NF-κB to promote the extracellular release of pro-inflammatory mediators. We further showed that low-dose naltrexone (LDN) abrogates hyperinsulinemia-mediated SIRT1 repression and prevents NF-κB p65 nuclear translocation. This, in turn, attenuates the hyperinsulinemia-induced release of pro-inflammatory cytokines and reinstates insulin sensitivity both in in vitro and in vivo diet-induced hyperinsulinemic mouse model. Notably, our data indicate that Sirt1 knockdown or inhibition blunts the anti-inflammatory properties of LDN in vitro. Using numerous complementary in silico and in vitro experimental approaches, we demonstrated that LDN can bind to SIRT1 and increase its deacetylase activity. Together, these data support a critical role of SIRT1 in inflammation and insulin resistance in hyperinsulinemia. LDN improves hyperinsulinemia-induced insulin resistance by reorienting macrophages toward anti-inflammation. Thus, LDN treatment may provide a novel therapeutic approach against hyperinsulinemia-associated insulin resistance.

scholarly journals Leptin as a Potential Regulator of FGF21

2016 ◽  
Vol 38 (3) ◽  
pp. 1218-1225 ◽  
Author(s):  
Mohamed Asrih ◽  
Christelle Veyrat-Durebex ◽  
Anne-Laure Poher ◽  
Jacqueline Lyautey ◽  
Françoise Rohner-Jeanrenaud ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepg2 Cells ◽  
Wistar Rats ◽  
Metabolic Diseases ◽  
Fibroblast Growth Factor 21 ◽  
New Findings ◽  
Expression Site ◽  
Fgf21 Expression

Background/Aims: Fibroblast growth factor 21 (FGF21), a potent metabolic regulator, has been shown to improve insulin sensitivity in animal models of insulin resistance. Several studies have focused on identifying mediators of FGF21 effects. However, the identification of factors involved in FGF21 regulation is far from complete. As leptin is a potent metabolic modulator as well, we aimed at characterizing whether leptin may regulate FGF21. Methods: We investigated a potential regulation of FGF21 by leptin in vivo in Wistar rats and in vitro using human derived hepatocarcinoma HepG2 cells. This model was chosen as the liver is considered the main FGF21 expression site. Results: We found that leptin injections increased plasma FGF21 levels in adult Wistar rats. This was confirmed in vitro, as leptin increased FGF21 expression in HepG2 cells. We also showed that the leptin effect on FGF21 expression was mediated by STAT3 activation in HepG2 cells. Conclusion: New findings regarding a leptin-STAT3-FGF21 axis were provided in this study, although investigating the exact mechanisms linking leptin and FGF21 are still needed. These results are of great interest in the context of identifying potential new clinical approaches to treat metabolic diseases associated with insulin resistance, such as obesity and type 2 diabetes.

scholarly journals Aberrant Ca2+ homeostasis in adipocytes links inflammation to metabolic dysregulation in obesity

2020 ◽  
Author(s):  
Ekin Guney ◽  
Ana Paula Arruda ◽  
Gunes Parlakgul ◽  
Erika Cagampan ◽  
Nina Min ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Dependent Manner ◽  
Metabolic Inflammation ◽  
Metabolic Dysregulation ◽  
Initiation And Propagation ◽  
Impaired Insulin Action

SummaryChronic metabolic inflammation is a key feature of obesity, insulin resistance and diabetes, although the initiation and propagation mechanisms of metaflammation are not fully established, particularly in the adipose tissue. Here we show that in adipocytes, altered regulation of the Ca2+ channel inositol triphosphate receptor (IP3Rs) is a key, adipocyte-intrinsic, event involved in the emergence and propagation of inflammatory signaling and the resulting insulin resistance. Inflammation, either induced by cytokine exposure in vitro or by obesity in vivo lead to increased expression and activity of IP3Rs in adipocytes in a JNK-dependent manner. This results in increased cytosolic Ca2+ and impaired insulin action. In mice, adipocyte-specific loss of IP3R1/2 protected against adipose tissue inflammation and insulin resistance despite significant diet-induced weight gain. Thus, this work reveals that IP3R over-activation and the resulting increase in cytosolic Ca2+ is a key link between obesity, inflammation and insulin resistance, and suggests that approaches to target adipocyte Ca2+ homeostasis may offer new therapeutic opportunities against metabolic diseases, especially since GWAS studies also implicate this locus in human obesity.

The depressing (negative) effect of oestradiol benzoate on the in vitro secretion of LH and FSH by the pituitary gland of the LRH-pretreated long-term ovariectomized rat changes into the augmentative (positive) effect after discontinuation of the LRH-pretreatment

1985 ◽  
Vol 110 (3) ◽  
pp. 329-337 ◽  
Author(s):  
G. A. Schuiling ◽  
H. Moes ◽  
T. R. Koiter
Keyword(s):  
Depressing Effect ◽  
Ovx Rats ◽  
Gonadotrophin Secretion ◽  
Oestradiol Benzoate ◽  
Negative Effect ◽  
Positive Effect ◽  
Perifusion System

Abstract. The effect of pretreatment in vivo with oestradiol benzoate on in vitro secretion of LH and FSH was studied in long-term ovariectomized (OVX) rats both at the end of a 5-day continuous in vivo pretreatment with LRH and 4-days after cessation of such LRH pretreatment. Rats were on day 0 sc implanted with osmotic minipumps which released LRH at the rate of 250 ng/h. Control rats were implanted with a piece of silicone elastomer with the dimensions of a minipump. On days 2 and 4 the rats were injected with either 3 μg EB or with oil. On day 5 part of the rats were decapitated and the in vitro autonomous (i.e. non-LRH-stimulated) and 'supra-maximally' LRHstimulated release of LH and FSH was studied using a perifusion system. From other rats the minipumps were removed on day 5 and perifusion was performed on day 9. On the 5th day of the in vivo LRH pretreatment the pituitary LH/FSH stores were partially depleted; the pituitaries of the EB-treated rats more so than those of the oil-injected rats. EB alone had no significant effect on the content of the pituitary LH- and FSH stores. On day 9, i.e. 4 days after removal of the minipumps, the pituitary LH and FSH contents had increased in both the oil- and the EB injected rats, but had not yet recovered to control values. In rats not subjected to the 5-days pretreatment with LRH EB had a positive effect on the supra-maximally LRH-stimulated secretion of LH and FSH as well as on the non-stimulated secretion of LH. EB had no effect on the non-stimulated secretion of FSH. After 5 days of in vivo pretreatment with LRH only, the in vitro non-stimulated and supra-maximally LRH-stimulated secretion of both LH and FSH were strongly impaired, the effect correlating well with the LRH-induced depletion of the pituitary LH/FSH stores. In such LRH-pretreated rats EB had on day 5 a negative effect on the (already depressed) LRH-stimulated secretion of LH (not on that of FSH). EB had no effect on the non-stimulated LH/FSH secretion. It could be demonstrated that the negative effect of the combined LRH/EB pretreatment was mainly due to the depressing effect of this treatment on the pituitary LH and FSH stores: the effect of oestradiol on the pituitary LRH-responsiveness (release as related to pituitary gonadotrophin content) remained positive. In LRH-pretreated rats, however, this positive effect of EB was smaller than in rats not pretreated with LRH. Four days after removal of the minipumps there was again a positive effect of EB on the LRH-stimulated secretion of LH and FSH as well as on the non-stimulated secretion of LH. The positive effect of EB on the pituitary LRH-responsiveness was as strong as in rats which had not been exposed to exogenous LRH. The non-stimulated secretion of FSH was again not affected by EB. The results demonstrate that the effect of EB on the oestrogen-sensitive components of gonadotrophin secretion consists of two components: an effect on the pituitary LRH-responsiveness proper, and an effect on the pituitary LH/FSH stores. The magnitude of the effect of EB on the LRH-responsiveness is LRH dependent: it is very weak (almost zero) in LRH-pretreated rats, but strong in rats not exposed to LRH as well as in rats of which the LRH-pretreatment was stopped 4 days previously. Similarly, the effect of EB on the pituitary LH and FSH stores is LRH-dependent: in the absence of LRH, EB has no influence on the contents of these stores, but EB can potentiate the depleting effect of LRH on the LH/FSH-stores. Also this effect disappear after cessation of the LRH-pretreatment.

Vitamin D as potential therapeutic anticancer agent

2018 ◽  
pp. 1-3
Keyword(s):  
Vitamin D ◽  
Anticancer Activity ◽  
Anticancer Agent ◽  
Antitumor Agents ◽  
Metastatic Potential ◽  
Anticancer Properties ◽  
Chemotherapy Agents

The role of vitamin D is implicated in carcinogenesis through numerous biological processes like induction of apoptosis, modulation of immune system inhibition of inflammation and cell proliferation and promotion of cell differentiation. Its use as additional adjuvant drug with cancer treatment may be novel combination for improved outcome of different cancers. Numerous preclinical, epidemiological and clinical studies support the role of vitamin D as an anticancer agent. Anticancer properties of vitamin D have been studied widely (both in vivo and in vitro) among various cancers and found to have promising results. There are considerable data that indicate synergistic potential of calcitriol and antitumor agents. Possible mechanisms for modulatory anticancer activity of vitamin D include its antiproliferative, prodifferentiating, and anti-angiogenic and apoptic properties. Calcitriol reduces invasiveness and metastatic potential of many cancer cells by inhibiting angiogenesis and regulating expression of the key molecules involved in invasion and metastasis. Anticancer activity of vitamin D is synergistic or additive with the antineoplastic actions of several drugs including cytotoxic chemotherapy agents like paclitaxel, docetaxel, platinum base compounds and mitoxantrone. Benefits of addition of vitamin D should be weighed against the risk of its toxicity.

Metabolomics of Healthy Berry Fruits

2019 ◽  
Vol 25 (37) ◽  
pp. 4888-4902 ◽  
Author(s):  
Gilda D'Urso ◽  
Sonia Piacente ◽  
Cosimo Pizza ◽  
Paola Montoro
Keyword(s):  
Biological Activities ◽  
Biologically Active ◽  
In Vivo Studies ◽  
Bioactive Metabolites ◽  
Active Metabolites ◽  
Positive Effects ◽  
Cell Functions ◽  
Berry Fruits

The consumption of berry-type fruits has become very popular in recent years because of their positive effects on human health. Berries are in fact widely known for their health-promoting benefits, including prevention of chronic disease, cardiovascular disease and cancer. Berries are a rich source of bioactive metabolites, such as vitamins, minerals, and phenolic compounds, mainly anthocyanins. Numerous in vitro and in vivo studies recognized the health effects of berries and their function as bioactive modulators of various cell functions associated with oxidative stress. Plants have one of the largest metabolome databases, with over 1200 papers on plant metabolomics published only in the last decade. Mass spectrometry (MS) and NMR (Nuclear Magnetic Resonance) are the most important analytical technologies on which the emerging ''omics'' approaches are based. They may provide detection and quantization of thousands of biologically active metabolites from a tissue, working in a ''global'' or ''targeted'' manner, down to ultra-trace levels. In the present review, we highlighted the use of MS and NMR-based strategies and Multivariate Data Analysis for the valorization of berries known for their biological activities, important as food and often used in the preparation of nutraceutical formulations.

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