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GENİSTEİNİN OBEZİTE ÜZERİNE ETKİSİ-THE EFFECT OF GENISTEIN ON OBESITY

March 2025

Conference: 6th International “ACHARAKA” Congress on Medicine, Nursing, Midwifery, and Health Sciences
At: İzmir, Türkiye

Authors:

Funda Işık

Kastamonu University

Kadriye Elif İmre

Kastamonu University

Content uploaded by Kadriye Elif İmre

Content may be subject to copyright.

6th International “ACHARAKA” Congress on Medicine, Nursing,

Midwifery, and Health Sciences Proceedings Book

ISBN: 978-625-6879-52-2

DOI: 10.5281/zenODO.10838601

528

GENİSTEİNİN OBEZİTE ÜZERİNE ETKİSİ

Funda Işık1*, Kadriye Elif İmre2

*1

2



ÖZET



  

           







            



          

  

           



         





        



           

           

  







Anahtar Kelimeler:

6th International “ACHARAKA” Congress on Medicine, Nursing,

Midwifery, and Health Sciences Proceedings Book ISBN: 978-625-6879-52-2

DOI: 10.5281/zenODO.10838601

529

THE EFFECT OF GENISTEIN ON OBESITY

ABSTRACT

  







   

     









     







           

      









           

  



Keywords: 

GİRİŞ



.

             

   

              

        



       





 



           

          





6th International “ACHARAKA” Congress on Medicine, Nursing,

Midwifery, and Health Sciences Proceedings Book

ISBN: 978-625-6879-52-2

DOI: 10.5281/zenODO.10838601

530

Genisteinin Obezite Üzerine Etki Mekanizmaları







           



         



         

 



         

          

          





        

           

           









          

        



         

            

  

 



         





     





          







  



6th International “ACHARAKA” Congress on Medicine, Nursing,

Midwifery, and Health Sciences Proceedings Book ISBN: 978-625-6879-52-2

DOI: 10.5281/zenODO.10838601

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           



  



            

              



          













Genisteinin Obezite Üzerine Etkileri ile İlgili Çalışma Bulguları





  

 

       

         











          

 













 









  

  









6th International “ACHARAKA” Congress on Medicine, Nursing,

Midwifery, and Health Sciences Proceedings Book

ISBN: 978-625-6879-52-2

DOI: 10.5281/zenODO.10838601

532



   



 









         





    





SONUÇ VE ÖNERİLER

      





           

         

         







KAYNAKÇA

-



-

-



  



   



    





 Journal of Advances in Medical and Biomedical

Research28

     



6th International “ACHARAKA” Congress on Medicine, Nursing,

Midwifery, and Health Sciences Proceedings Book ISBN: 978-625-6879-52-2

DOI: 10.5281/zenODO.10838601

533

-



-







-









      





     







-



   



  -







Journal of Food Biochemistry46



Diabetes, Metabo-

lic Syndrome and Obesity: Targets and Therapy









 





toxicologi-

cal sciences138











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6th International “ACHARAKA” Congress on Medicine, Nursing,

Midwifery, and Health Sciences Proceedings Book

ISBN: 978-625-6879-52-2

DOI: 10.5281/zenODO.10838601

534

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The obesogenic side of Genistein

Article

Full-text available

Nov 2023

Genistein (GN) has been highly recommended for its medicinal properties like anticancer, antidiabetic, antihyperlipidemic, antiviral, and antioxidant activities among others. Recently, scientists realized that Genistein is an endocrine disruptor. It is an obesogen that interferes with the endocrine system causing obesity through many mechanisms like inducing adipocyte differentiation, lipid accumulation, and transformation of some stem cells into adipocytes (bone marrow mesenchymal stem cells for example) in vitro. Animal studies show that GN upregulates genes associated with adipogenesis like CCAAT/enhancer binding protein alpha (Cebpα), CCAAT/enhancer binding protein beta (Cebpβ), and PPARγ. In silico studies reveal a strong binding affinity for estrogen receptors. All these findings were contingent on concentration and tissues. It is beyond dispute that obesity is one of the most frustrating medical conditions under the sun. The pathophysiology of this disease was first attributed to a high-calorie diet and lack of physical activity. However, studies proved that these two factors are not enough to account for obesity in both children and adults. This mini review highlights how Genistein interaction with the peroxisome proliferator-activated receptor gamma protein can cause obesity.

Anti-obesity properties and mechanism of action of genistein

Article

Full-text available

Jul 2023

Obesity is considered a major health problem worldwide with a constantly increasing incidence, representing a significant public health issue affecting all genders and all ages, even children. The WHO reports alarming information that in 2016, 39% of adults were overweight, 13% were obese, and more than 340 million children and adolescents were overweight or obese. Information from 2020 states that 39 million children under 5 years of age were overweight or obese. With the occurrence of obesity, the risk obesity-related disease incidence, for example, hypertension, stroke, myocardial infarction, diabetes mellitus, fatty liver, osteoarthritis, obstructive sleep apnoea, dementia, and several types of cancer, greatly increases.Recent evidence shows the beneficial effects of natural compounds - flavonoids in preventing and treating obesity. Flavonoids, found in various plants, represent active biocompounds that are associated with many beneficial effects on human health, including their noticeable effect in obesity treatment due to their ability to reduce food intake and increase energy expenditure, reduce fat absorption and fat mass, decrease levels of triacylglycerides and cholesterol, and modulate the metabolism of lipids. Our review summarizes the antiobesity effect of genistein, a flavonoid that belongs to isoflavones subgroups. Genistein, a naturally occurring compound, is one of the most known and studied isoflavones that shows many beneficial antiobesity properties. Genistein has the ability to reduce body weight and food intake, increase lipolysis, increase oxidation of fatty acids, decrease adipogenesis, stimulate adipocyte differentiation, and induce adipocyte apoptosis.Keywords: Obesity, Flavonoids, Isolavone, Genistein

Therapeutic potentials of genistein: New insights and perspectives

Article

Full-text available

May 2022
J FOOD BIOCHEM

Genistein, a polyphenolic isoflavone compound found abundantly in soy or soy‐based products, is widely consumed in the Asian population. Genistein has poor bioavailability, to overcome this problem many advanced nano‐drug delivery carrier systems are designed to enhance its water solubility and stability. However, further research is required to develop more efficient bioavailability improvement strategies. Genistein is a phytoestrogen which has been associated with reducing the risk of cancer, cardiovascular disorders, and diabetes mellitus. This plant‐based bioactive compound possesses numerous biological activities such as anti‐oxidant, anti‐inflammatory, anti‐obesity, anti‐cancer, cardioprotective, and anti‐diabetic activities to treat various disease states. Genistein has been used as an active therapeutic agent in many medications. Moreover, several clinical trials are in the ongoing stage to develop more efficient treatment therapies, especially for cancer treatment. This article highlights the protective and therapeutic benefits of genistein in the treatment of different ailments, and more specifically elaborates on the anti‐cancer potential of genistein regarding various types of cancers. Practical applications Genistein possesses versatile biological activities, including anti‐diabetic, anti‐inflammatory, anti‐oxidant, anti‐obesity, and anti‐angiogenic. The most studied activity is anti‐cancer. Currently, a number of pre‐clinical and clinical trials are being carried out on anti‐neoplastic and cytotoxic activities of genistein to develop novel therapeutic agents with excellent anti‐cancer potential for the treatment of various kinds of cancer. Moreover, many bioavailability enhancement strategies have been developed to improve the bioavailability of genistein. Genistein shows significant hypoglycemic effects alone or in combination with other anti‐diabetic agents. Genistein in combination with other chemotherapeutic agents is used for the treatment of prostate, bone, colorectal, glioma, breast, and bladder cancer.

Genistein Alleviates High-Fat Diet-Induced Obesity by Inhibiting the Process of Gluconeogenesis in Mice

Article

Full-text available

Apr 2022

Genistein is an isoflavone phytoestrogen that has been shown to improve obesity; however, the underlying molecular mechanisms involved therein have not been clearly elucidated. In this study, we administered genistein to high-fat diet-induced obese mice to investigate its effect on hepatic gluconeogenesis. The results showed that genistein treatment significantly inhibited body weight gain, hyperglycemia, and adipose and hepatic lipid deposition in high-fat diet-induced obese mice. Glucose tolerance test (GTT), insulin tolerance test (ITT) and pyruvate tolerance test (PTT) showed that genistein treatment significantly inhibited gluconeogenesis and improved insulin resistance in obese mice. In addition, this study also found that genistein could promote the expression of miR-451 in vitro and in vivo, and the dual-luciferase reporter system showed that G6pc (glucose-6-phosphatase) may be a target gene of miR-451. Both genistein treatment and in vivo injection of miR-451 agomir significantly inhibited gluconeogenesis and inhibited the expression of G6pc and Gk (glycerol kinase, a known target gene of miR-451). In conclusion, genistein may inhibit gluconeogenesis in obese mice by regulating the expression of Gk and G6pc through miR-451. These results may provide insights into the functions of miR-451 and food-derived phytoestrogens in ameliorating and preventing gluconeogenesis-related diseases.

Cellular and molecular mechanisms of genistein in prevention and treatment of diseases: An overview

Article

Full-text available

Oct 2021
J FOOD BIOCHEM

Genistein is the simplest secondary metabolite in soybeans and belongs to a group of compounds called isoflavones. It is a phytoestrogen and it makes up more than 60% of soy isoflavones. Studies have shown the anti-inflammatory, anti-apoptotic, and anti-angiogenic effects of genistein in addition to its modulatory effects on steroidal hormone receptors. In this review, we discuss the pharmacologic and therapeutic effects of genistein on various diseases. Practical applications In this review, we have discussed the therapeutic effects of genistein as the main constituent of soybeans on health conditions. Its antioxidant, anti-inflammatory, anti-apoptotic and, anti-angiogenic effects need more attention. The pharmacological properties of genistein make this natural isoflavone a potential treatment for various diseases such as postmenopausal symptoms, cancer, bone, brain, and heart diseases. Special emphasis should be given to it, resulting in using it in clinical as a safe, potent, and bioactive molecule.

Genistein as a regulator of signaling pathways and microRNAs in different types of cancers

Article

Full-text available

Jul 2021
Canc Cell Int

Cancers are complex diseases orchestrated by a plethora of extrinsic and intrinsic factors. Research spanning over several decades has provided better understanding of complex molecular interactions responsible for the multifaceted nature of cancer. Recent advances in the field of next generation sequencing and functional genomics have brought us closer towards unravelling the complexities of tumor microenvironment (tumor heterogeneity) and deregulated signaling cascades responsible for proliferation and survival of tumor cells. Phytochemicals have begun to emerge as potent beneficial substances aimed to target deregulated signaling pathways. Isoflavonoid genistein is an essential phytochemical involved in regulation of key biological processes including those in different types of cancer. Emerging preclinical evidence have shown its anti-cancer, anti-inflammatory and anti-oxidant properties. Testing of this substance is in various phases of clinical trials. Comprehensive preclinical and clinical trials data is providing insight on genistein as a modulator of various signaling pathways both at transcription and translation levels. In this review we have explained the mechanistic regulation of several key cellular pathways by genistein. We have also addressed in detail various microRNAs regulated by genistein in different types of cancer. Moreover, application of nano-formulations to increase the efficiency of genistein is also discussed. Understanding the pleiotropic potential of genistein to regulate key cellular pathways and development of efficient drug delivery system will bring us a step towards designing better chemotherapeutics.

Natural compounds as obesity pharmacotherapies

Article

Dec 2023
PHYTOTHER RES

Obesity has become a serious global public health problem, affecting over 988 million people worldwide. Nevertheless, current pharmacotherapies have proven inadequate. Natural compounds have garnered significant attention due to their potential antiobesity effects. Over the past three decades, ca. 50 natural compounds have been evaluated for the preventive and/or therapeutic effects on obesity in animals and humans. However, variations in the antiobesity efficacies among these natural compounds have been substantial, owing to differences in experimental designs, including variations in animal models, dosages, treatment durations, and administration methods. The feasibility of employing these natural compounds as pharmacotherapies for obesity remained uncertain. In this review, we systematically summarized the antiobesity efficacy and mechanisms of action of each natural compound in animal models. This comprehensive review furnishes valuable insights for the development of antiobesity medications based on natural compounds.

Genistein enhances NAD+ biosynthesis by upregulating nicotinamide phosphoribosyltransferase in adipocytes

Article

Aug 2023
J NUTR BIOCHEM

A decrease in the NAD+ level in adipocytes causes adipose-tissue dysfunction, leading to systemic glucose and lipid metabolism failure. Therefore, it is necessary to develop small molecules and nutraceuticals that can increase NAD+ levels in adipocytes. Genistein, a nutraceutical derived from soybeans, has various physiological activities and improves glucose and lipid metabolism. In this study, we aimed to unravel the effects of genistein on the NAD+ level in adipocytes and the underlying molecular mechanisms. Genistein enhanced NAD+ biosynthesis by increasing the expression of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD+ biosynthesis. A pull-down assay using genistein-immobilized beads revealed prohibitin 1 (PHB1) as a target protein of genistein. The knockdown of Phb1 suppressed the genistein-induced increase in NAMPT expression and NAD+ level in adipocytes. Genistein-bound PHB1 contributed to the stabilization of the transcription factor CCAAT/enhancer-binding protein β through the activation of extracellular signal-regulated kinase, resulting in increased NAMPT expression at the transcriptional level. Genistein induced the dephosphorylation of peroxisome proliferator-activated receptor at serine 273 and increased the level of the insulin-sensitizing adipokine adiponectin in adipocytes, whereas the knockdown of Nampt and Phb1 abolished these genistein-mediated effects. Our results proved the potential efficacy of genistein in increasing the NAD+ level and restoring metabolic function in adipocytes. Furthermore, we identified PHB1, localized to the plasma membrane, as a novel candidate target protein for increased expression of NAMPT in adipocytes. Overall, these findings will assist in developing NAD+-boosting nutraceuticals to alleviate metabolic dysfunctions in adipose tissues.

Genistein Stimulation of White Adipose Tissue Thermogenesis Is Partially Dependent on GPR30 in Mice

Article

Feb 2022

Scope: Genistein increases whole body energy expenditure by stimulating white adipose tissue (WAT) browning and thermogenesis. G-Coupled receptor GPR30 can mediate some actions of genistein, however, it is not known whether it is involved in the activation of WAT-thermogenesis. Thus, the aim of the study was to determine whether genistein activates thermogenesis coupled to an increase in WAT browning and mitochondrial activity, in GPR30+/+ and GPR30-/- mice. Methods and results: GPR30+/+ and GPR30-/- mice were fed control or high fat sucrose diets containing or not genistein for 8 weeks. Body weight and composition, energy expenditure, glucose tolerance and browning markers in WAT, and oxygen consumption rate, 3', 5'-cyclic adenosine monophosphate (cAMP) concentration and browning markers in adipocytes were evaluated. Genistein consumption reduced body weight and fat mass gain in a different extent in both genotypes, however, energy expenditure was lower in GPR30-/- compared to GPR30+/+ mice, accompanied by a reduction in browning markers, maximal mitochondrial respiration, cAMP concentration and browning markers in cultured adipocytes from GPR30-/- mice. Genistein improved glucose tolerance in GPR30+/+ , but this was partially observed in GPR30-/- mice. Conclusion: Our results showed that GPR30 partially mediates genistein stimulation of WAT thermogenesis and the improvement of glucose tolerance. This article is protected by copyright. All rights reserved.

Genistein improves systemic metabolism and enhances cold resistance by promoting adipose tissue beiging

Article

Apr 2021
BIOCHEM BIOPH RES CO

Genistein, a naturally occurring phytoestrogen and a member of the large class of compounds known as isoflavones, exerts protective effects in several diseases. Recent studies indicate that genistein plays a critical role in controlling body weight, obesity-associated insulin resistance, and metabolic disorders, but its target organs in reversing obesity and related pathological conditions remain unclear. In this study, we showed that mice supplemented with 0.2% genistein in a high-fat diet for 12 weeks showed enhanced metabolic homeostasis, including reduced obesity, improved glucose uptake and insulin sensitivity, and alleviated hepatic steatosis. We also observed a beiging phenomenon in the white adipose tissue and reversal of brown adipose tissue whitening in these mice. These changes led to enhanced resistance to cold stress. Altogether, our data suggest that the improved metabolic profile in mice treated with genistein is likely a result of enhanced adipose tissue function.