Endometrial cancer(EC)is a malignant tumour that occurs in the epithelial cells of the endometrium and represents one of the most common malignancies involving the female reproductive system,with endometrioid adenocar...Endometrial cancer(EC)is a malignant tumour that occurs in the epithelial cells of the endometrium and represents one of the most common malignancies involving the female reproductive system,with endometrioid adenocarcinoma as the most common type.In recent years,with an increasingly aging society and the growing number of obese people,the incidence of EC is constantly rising,posing a serious threat to women’s health.Some studies have reported that the interruption of digestion and absorption caused by imbalance in intestinal microbiota may lead to conditions such as obesity,hypertension,diabetes,and hormone imbalance,which are all risk factors for EC.Meanwhile,intestinal bacteria produce a series of metabolites during colonization and reproduction,which can rapidly respond to changes in the microenvironment of the body.Changes in their types and quantities can serve as sensitive indicators of physiological and pathological changes in the body.Patients with EC often suffer from metabolic diseases,which can lead to metabolic disorders involving carbohydrates,fats,and amino acid in their bodies.展开更多
Leptin is an adipokine that has been linked with the cardiovascular complications resulting from obesity such as hypertension and heart disease. Obese patients have high levels of circulating leptin due to increased f...Leptin is an adipokine that has been linked with the cardiovascular complications resulting from obesity such as hypertension and heart disease. Obese patients have high levels of circulating leptin due to increased fat mass. Clinical and population studies have correlated high levels of circulating leptin with the development of cardiac hypertrophy in obesity. Leptin has also been demonstrated to increase the growth of cultured cardiomyocytes. However, several animal studies of obese leptin deficient mice have not supported a role for leptin in promoting cardiac hypertrophy so the role of leptin in this pathological process remains unclear. Leptin is also an important hormone in the regulation of cardiac metabolism where it supports oxidation of glucose and fatty acids. In addition, leptin plays a critical role in protecting the heart from excess lipid accumulation and the formation of toxic lipids in obesity a condition known as cardiac lipotoxicity. This paper focuses on the data supporting and refuting leptin's role in promoting cardiac hypertrophy as well as its important role in the regulation of cardiac metabolism and protection against cardiac lipotoxicity.展开更多
Background: A leptin-like immunoreactive substance has been found in chicken eggs and has been implicated in serving as a maternal signal to program offspring growth and metabolism. In the present study, we investiga...Background: A leptin-like immunoreactive substance has been found in chicken eggs and has been implicated in serving as a maternal signal to program offspring growth and metabolism. In the present study, we investigated the effects of in ovo leptin administration on hatch weight, serum and hepatic concentrations of metabolites and hormones, as well as on the expression of genes involved in hepatic lipid metabolism and the predicted microRNAs (miRNAs) targeting the affected genes. To this end we injected fertile eggs with either 0.5 μg of recombinant murine leptin or vehicle (PBS) before incubation.Results: Prenatally leptin-exposed chicks showed lower hatch weight, but higher liver weight relative to the body weight, compared to the control group. In ovo leptin treatment increased the hepatic content and serum concentration of leptin in newly hatched chickens. The hepatic contents of triglycerides (TG) and total cholesterol (Tch) were decreased, whereas the serum levels of TG, Tch and apolipoprotein B (ApoB) were increased. The hepatic mRNA expression of sterol regulator element binding protein 1 (SREBP-1c), SREBP-2, hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and cholesterol 7a-hydroxylase 1 (CYP7A1) was significantly up-regulated, as was the protein content of both SREBP-1 c and SREBP-2 in hepatic nuclear extracts of leptin-treated chickens. Moreover, out of 12 miRNAs targeting SREBP-1c and/or HMGCR, five were significantly up-regulated in liver of leptin-treated chicks, including gga-miR-200b and gga-miR-429, which target both SREBP-1c and HMGCR.Conclusions: These results suggest that leptin in ovo decreases hatch weight, and modifies hepatic leptin secretion and lipid metabolism in newly hatched broiler chickens, possibly via microRNA-mediated gene regulation.展开更多
AIM: To determine serum leptin levels and investigate their correlations with anthropometric and metabolic parameters and biochemical liver function in patients with chronic hepatitis C virus (HCV) infection and their...AIM: To determine serum leptin levels and investigate their correlations with anthropometric and metabolic parameters and biochemical liver function in patients with chronic hepatitis C virus (HCV) infection and their potential clinical implications.METHODS: Forty-two chronic HCV-infected patients without anti-viral treatment were enrolled in this study, 30 patients had chronic hepatitis C, 10 had cirrhosis, and 2 had hepatocellular carcinoma (HCC). Thirty age- and sex-matched healthy individuals served as controls. Serum leptin levels were determined by ELISA. The biochemical liver function and serum lipids were determined at the same time. The height and body weight of patients and controls were measured, and body mass index (BMI) and body fat were calculated simultaneously. The correlations of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function were assessed statistically.RESULTS: The mean of serum leptin levels in patients with chronic hepatitis C, HCV-associated cirrhosis, HCVassociated HCC and control groups was (6.13±3.94),(5.25±4.21), (4.17±0.28), and (3.59±3.44) ng/mL, respectively. The serum leptin level in patients with chronic hepatitis C was significantly higher than that in controls. The serum leptin levels between cirrhotic patients and controls and between male and female cirrhotic patients had no significant difference. Serum leptin levels were positively-correlated with body fat, BMI, and apolipoprotein B (Apo B) in patients with chronic HCV infection. The serum alanine aminotransferase (ALT) levels were closelycorrelated with BMI in patients with chronic hepatitis C. CONCLUSION: HCV infection interferes with fat and lipid metabolism in patients with chronic HCV infection and leptin may play a role in hepatosteatosis.展开更多
BACKGROUND Insulin resistance(IR)and impaired energy expenditure(IEE)are irreparable metabolic comorbidities in schizophrenia.Although mechanism(s)underlying IR and IEE remains unclear,leptin and fatty acid signaling,...BACKGROUND Insulin resistance(IR)and impaired energy expenditure(IEE)are irreparable metabolic comorbidities in schizophrenia.Although mechanism(s)underlying IR and IEE remains unclear,leptin and fatty acid signaling,which has profound influence on insulin secretion/sensitivity,glucose metabolism and energy expenditure,could be disrupted.However,no association of plasma leptin with erythrocyte membrane fatty acids,body mass index(BMI),and psychotic symptoms in the same cohort of untreated patients with first-episode psychosis(FEP)or medicated patients with chronic schizophrenia(CSZ)is presented before.These studies are crucial for deciphering the role of leptin and fatty acids in the development of IR and IEE in schizophrenia.AIM To determine the association between plasma leptin,erythrocyte membrane fatty acids,particularly,saturated fatty acids(SFAs),BMI and psychotic symptoms in patients with FEP and CSZ.METHODS In this study,twenty-two drug naive patients with FEP,twenty-one CSZ patients treated with atypical antipsychotic drugs,and fourteen healthy control(CNT)subjects were analyzed.Plasma leptin was measured using sandwich mode enzyme-linked immunosorbent assay.Erythrocyte membrane SFAs were measured using ultrathin capillary gas chromatography.BMI was calculated by using the formula:weight(kg)/height(m^(2)).Psychiatric symptoms were evaluated at baseline using brief psychiatric rating scale(BPRS),and positive and negative syndrome scale(PANSS).The total BPRS scores,positive and negative symptom scores(PANSS-PSS and PANSS-NSS,respectively)were recorded.Pearson correlation coefficient(r)analyses were performed to find the nature and strength of association between plasma leptin,PANSS scores,BMI and SFAs,particularly,palmitic acid(PA).RESULTS In patients with FEP,plasma leptin not BMI was significantly lower(P=0.034),whereas,erythrocyte membrane SFAs were significantly higher(P<0.005)compared to the CNT subjects.Further,plasma leptin showed negative correlation with erythrocyte membrane SFAs-PA(r=-0.4972,P=0.001),PANSS-PSS(r=-0.4034,P=0.028),and PANSS-NSS(r=-0.3487,P=0.048).However,erythrocyte membrane SFAs-PA showed positive correlation with PANSS-PSS(r=0.5844,P=0.0034)and PANSS-NSS(r=0.5380,P=0.008).In CSZ patients,plasma leptin,BMI,and erythrocyte membrane SFAs,all were significantly higher(P<0.05)compared to the CNT subjects.Plasma leptin showed positive correlation with BMI(r=0.312,P=0.032)but not with PANSS scores or erythrocyte membrane SFAs-PA.However,erythrocyte membrane SFAs-PA showed positive correlation with PANSS-NSS only(r=0.4729,P=0.031).Similar changes in the plasma leptin and erythrocyte membrane SFAs have also been reported in individuals at ultrahigh risk of developing psychosis;therefore,the above findings suggest that leptin-fatty acid biosynthesis could be disrupted before the onset of psychosis in schizophrenia.CONCLUSION Disrupted leptin-fatty acid biosynthesis/signaling could be an early manifestation of metabolic comorbidities in schizophrenia.Large-scale studies are warranted to validate the above findings.展开更多
Kashin-Beck disease(KBD)is a chronic,endemic,degenerative osteoarthropathic condition that is predominantly found in China's Mainland.KBD is a progressive disease,and the signs and symptoms become more severe in a...Kashin-Beck disease(KBD)is a chronic,endemic,degenerative osteoarthropathic condition that is predominantly found in China's Mainland.KBD is a progressive disease,and the signs and symptoms become more severe in adulthood owing to the continuous development of lesions in the joint cartilage[1].Although childhood KBD has largely been controlled,adult KBD is an important health concern in rural regions.Unfortunately,in the last century,many adult KBD patients still remain during serious epidemics.展开更多
Objective: The elevated incidence of obesity has been paralleled with higher risks of breast cancer. High adiposity increases leptin secretion from adipose tissue, which in turn increases cancer cell proliferation. Th...Objective: The elevated incidence of obesity has been paralleled with higher risks of breast cancer. High adiposity increases leptin secretion from adipose tissue, which in turn increases cancer cell proliferation. The interplay between leptin and estrogen is one of the mechanisms through which leptin influences breast carcinogenesis. An unbalanced estrogen metabolism increases the formations of catechol estrogen quinones, DNA adducts, and cancer mutations. This study aims to investigate the effect of leptin on some estrogen metabolic enzymes and DNA adduction in breast cancer cells.Methods: High performance liquid chromatography(HPLC) was performed to analyze the DNA adducts 4-OHE1[E2]-1-N3 adenine and 4-OHE1[E2]-1-N7 guanine. Reporter gene assay, real time reverse transcription polymerase chain reaction(real time RT-PCR), and Western blot were used to assess the expression of estrogen metabolizing genes and enzymes: Cytochrome P-4501B1(CYP1B1), Nicotinamide adenine dinucleotide phosphate-quinone oxidoreductase1(NQO1), and Catechol-O-methyl transferase(COMT).Results: Leptin significantly increased the DNA adducts 4-OHE1[E2]-1-N3 adenine and 4-OHE1[E2]-1-N7 guanine.Furthermore, leptin significantly upregulated CYP1B1 promoter activity and protein expression. The luciferase promoter activities of NQO1 and m RNA levels were significantly reduced. Moreover, leptin greatly reduced the reporter activities of the COMT-P1 and COMT-P2 promoters and diminished the protein expression of COMT.Conclusions: Leptin increases DNA adduct levels in breast cancer cells partly by affecting key genes and enzymes involved in estrogen metabolism. Thus, increased focus should be directed toward leptin and its effects on the estrogen metabolic pathway as an effective approach against breast cancer.展开更多
Numerous instances of poisoning caused by the ingestion of mushrooms are reported annually worldwide,with most mushroom poisoning deaths caused by the ingestion of toxic amanita fungi.Amatoxin is the main toxic compon...Numerous instances of poisoning caused by the ingestion of mushrooms are reported annually worldwide,with most mushroom poisoning deaths caused by the ingestion of toxic amanita fungi.Amatoxin is the main toxic component of amanita,andα-amanitin is one of the most potent toxins present in amatoxin[1].展开更多
Alzheimer’s disease (AD) is the leading neurodegenerative disorder globally.Despite this,there is minimal effective therapeutics proven to reduce or prevent the progression of this disease.Glutamate is the main excit...Alzheimer’s disease (AD) is the leading neurodegenerative disorder globally.Despite this,there is minimal effective therapeutics proven to reduce or prevent the progression of this disease.Glutamate is the main excitatory neurotransmitter within the central nervous system and plays a crucial role in neuronal and synaptic functions.展开更多
Background: Obesity is rising globally, independent of ethnicity, race and age, and is associated with increased risk of cardiovascular mortality and morbidity especially in persons living with diabetes. The effect of...Background: Obesity is rising globally, independent of ethnicity, race and age, and is associated with increased risk of cardiovascular mortality and morbidity especially in persons living with diabetes. The effect of adipokines such as leptin, resistin and adiponectin which are secreted by adipose tissue factors has been linked to the increased risk of the cardiovascular mortality and morbidity. Aim: This study aims to assess the levels of serum leptin and serum adiponectin in obese type 2 diabetes subjects, and their relationship with cardio-metabolic component (using lipid profile). Method: This is a cross-sectional comparative hospital-based study in which one hundred and fifty participants grouped into 60 obese, 60 non-obese none diabetic and 30 non-obese non-diabetic adults with similar age from the Endocrinology outpatient’s clinic, General outpatient department (GOPD) and staff clinic of Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC). Anthropometric parameters and other relevant clinical details of all subjects were obtained. Fasting venous blood samples were taken from all subjects for the determination of fasting plasma glucose (FPG), fasting lipid profile, glycosylated haemoglobin levels (HbA<sub>1C</sub>), fasting serum insulin, leptin, and adiponectin. Data was analysed using the Statistical Package of Social Sciences (SPSS) version 23.0. Results: Twenty-eight (46.7%)) subjects were males while 32 subjects (53.3%) were females (in obese groups). There was no statistical difference between these two groups for both sexes (p = 1.000). The age range for all subjects was 34 to 64 years with their mean age being 52 ± 7.3 years, and for type 2 subjects and the obese non-diabetic 50.7 ± 7.3 years respectively. The mean body mass index of the non-obese and non-diabetic was 23.7 ± 4 Kg/m<sup>2</sup> while the anthropometric measurements of the obese two groups were similar. The lipid profile, serum leptin and adiponectin in both the obese groups showed no difference. The relationship between components of obesity and serum leptin level in all subjects showed that serum leptin levels had significant positive correlation with BMI, WC, and serum insulin level. The correlation between adiponectin and lipid profile showed a positive correlation between serum adiponectin values and High-density lipoprotein (HDL) in obese diabetic (p = 0.02) but not in the non-diabetic group. Conclusion: In this study, there was no correlation in the serum leptin levels with the anthropometric parameters of obesity studied. For the components of the lipid profile, Triglycerides and low-density lipoprotein cholesterol (LDL) correlated with serum adiponectin and HDL showed a positive correlation with adiponectin. It is concluded that the effects of both serum adiponectin and serum leptin are driven by obesity rather than the glycaemic status of the obese subjects.展开更多
基金funded by the Fundamental Research Program of Shanxi Province(Grant number 202103021224394).
文摘Endometrial cancer(EC)is a malignant tumour that occurs in the epithelial cells of the endometrium and represents one of the most common malignancies involving the female reproductive system,with endometrioid adenocarcinoma as the most common type.In recent years,with an increasingly aging society and the growing number of obese people,the incidence of EC is constantly rising,posing a serious threat to women’s health.Some studies have reported that the interruption of digestion and absorption caused by imbalance in intestinal microbiota may lead to conditions such as obesity,hypertension,diabetes,and hormone imbalance,which are all risk factors for EC.Meanwhile,intestinal bacteria produce a series of metabolites during colonization and reproduction,which can rapidly respond to changes in the microenvironment of the body.Changes in their types and quantities can serve as sensitive indicators of physiological and pathological changes in the body.Patients with EC often suffer from metabolic diseases,which can lead to metabolic disorders involving carbohydrates,fats,and amino acid in their bodies.
基金the National Heart,Lung and Blood Institute,Nos.PO1HL-051971 and R00HL112952the National Institute of General Medical Sciences,No.P20GM-104357the American Heart Association,No.14SDG20490339
文摘Leptin is an adipokine that has been linked with the cardiovascular complications resulting from obesity such as hypertension and heart disease. Obese patients have high levels of circulating leptin due to increased fat mass. Clinical and population studies have correlated high levels of circulating leptin with the development of cardiac hypertrophy in obesity. Leptin has also been demonstrated to increase the growth of cultured cardiomyocytes. However, several animal studies of obese leptin deficient mice have not supported a role for leptin in promoting cardiac hypertrophy so the role of leptin in this pathological process remains unclear. Leptin is also an important hormone in the regulation of cardiac metabolism where it supports oxidation of glucose and fatty acids. In addition, leptin plays a critical role in protecting the heart from excess lipid accumulation and the formation of toxic lipids in obesity a condition known as cardiac lipotoxicity. This paper focuses on the data supporting and refuting leptin's role in promoting cardiac hypertrophy as well as its important role in the regulation of cardiac metabolism and protection against cardiac lipotoxicity.
基金supported by the NSFC-Guangdong Joint Fund (U0931004)the Sino-German Cooperation in Agriculture (Project No. 28/04-05CHN7,2010-2011)+4 种基金the Special Fund for Agro-scientific Research in the Public Interest (201003011)the National "948" project (2011-S11)the Natural Science Foundation of Jiangsu Province (BK2010296)the Doctor Foundation of the Institute of Poultry Science of Jiangsu Province (JQ201001)the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Background: A leptin-like immunoreactive substance has been found in chicken eggs and has been implicated in serving as a maternal signal to program offspring growth and metabolism. In the present study, we investigated the effects of in ovo leptin administration on hatch weight, serum and hepatic concentrations of metabolites and hormones, as well as on the expression of genes involved in hepatic lipid metabolism and the predicted microRNAs (miRNAs) targeting the affected genes. To this end we injected fertile eggs with either 0.5 μg of recombinant murine leptin or vehicle (PBS) before incubation.Results: Prenatally leptin-exposed chicks showed lower hatch weight, but higher liver weight relative to the body weight, compared to the control group. In ovo leptin treatment increased the hepatic content and serum concentration of leptin in newly hatched chickens. The hepatic contents of triglycerides (TG) and total cholesterol (Tch) were decreased, whereas the serum levels of TG, Tch and apolipoprotein B (ApoB) were increased. The hepatic mRNA expression of sterol regulator element binding protein 1 (SREBP-1c), SREBP-2, hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and cholesterol 7a-hydroxylase 1 (CYP7A1) was significantly up-regulated, as was the protein content of both SREBP-1 c and SREBP-2 in hepatic nuclear extracts of leptin-treated chickens. Moreover, out of 12 miRNAs targeting SREBP-1c and/or HMGCR, five were significantly up-regulated in liver of leptin-treated chicks, including gga-miR-200b and gga-miR-429, which target both SREBP-1c and HMGCR.Conclusions: These results suggest that leptin in ovo decreases hatch weight, and modifies hepatic leptin secretion and lipid metabolism in newly hatched broiler chickens, possibly via microRNA-mediated gene regulation.
基金Supported by the National Natural Science Foundation of China, No. 30170842
文摘AIM: To determine serum leptin levels and investigate their correlations with anthropometric and metabolic parameters and biochemical liver function in patients with chronic hepatitis C virus (HCV) infection and their potential clinical implications.METHODS: Forty-two chronic HCV-infected patients without anti-viral treatment were enrolled in this study, 30 patients had chronic hepatitis C, 10 had cirrhosis, and 2 had hepatocellular carcinoma (HCC). Thirty age- and sex-matched healthy individuals served as controls. Serum leptin levels were determined by ELISA. The biochemical liver function and serum lipids were determined at the same time. The height and body weight of patients and controls were measured, and body mass index (BMI) and body fat were calculated simultaneously. The correlations of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function were assessed statistically.RESULTS: The mean of serum leptin levels in patients with chronic hepatitis C, HCV-associated cirrhosis, HCVassociated HCC and control groups was (6.13±3.94),(5.25±4.21), (4.17±0.28), and (3.59±3.44) ng/mL, respectively. The serum leptin level in patients with chronic hepatitis C was significantly higher than that in controls. The serum leptin levels between cirrhotic patients and controls and between male and female cirrhotic patients had no significant difference. Serum leptin levels were positively-correlated with body fat, BMI, and apolipoprotein B (Apo B) in patients with chronic HCV infection. The serum alanine aminotransferase (ALT) levels were closelycorrelated with BMI in patients with chronic hepatitis C. CONCLUSION: HCV infection interferes with fat and lipid metabolism in patients with chronic HCV infection and leptin may play a role in hepatosteatosis.
文摘BACKGROUND Insulin resistance(IR)and impaired energy expenditure(IEE)are irreparable metabolic comorbidities in schizophrenia.Although mechanism(s)underlying IR and IEE remains unclear,leptin and fatty acid signaling,which has profound influence on insulin secretion/sensitivity,glucose metabolism and energy expenditure,could be disrupted.However,no association of plasma leptin with erythrocyte membrane fatty acids,body mass index(BMI),and psychotic symptoms in the same cohort of untreated patients with first-episode psychosis(FEP)or medicated patients with chronic schizophrenia(CSZ)is presented before.These studies are crucial for deciphering the role of leptin and fatty acids in the development of IR and IEE in schizophrenia.AIM To determine the association between plasma leptin,erythrocyte membrane fatty acids,particularly,saturated fatty acids(SFAs),BMI and psychotic symptoms in patients with FEP and CSZ.METHODS In this study,twenty-two drug naive patients with FEP,twenty-one CSZ patients treated with atypical antipsychotic drugs,and fourteen healthy control(CNT)subjects were analyzed.Plasma leptin was measured using sandwich mode enzyme-linked immunosorbent assay.Erythrocyte membrane SFAs were measured using ultrathin capillary gas chromatography.BMI was calculated by using the formula:weight(kg)/height(m^(2)).Psychiatric symptoms were evaluated at baseline using brief psychiatric rating scale(BPRS),and positive and negative syndrome scale(PANSS).The total BPRS scores,positive and negative symptom scores(PANSS-PSS and PANSS-NSS,respectively)were recorded.Pearson correlation coefficient(r)analyses were performed to find the nature and strength of association between plasma leptin,PANSS scores,BMI and SFAs,particularly,palmitic acid(PA).RESULTS In patients with FEP,plasma leptin not BMI was significantly lower(P=0.034),whereas,erythrocyte membrane SFAs were significantly higher(P<0.005)compared to the CNT subjects.Further,plasma leptin showed negative correlation with erythrocyte membrane SFAs-PA(r=-0.4972,P=0.001),PANSS-PSS(r=-0.4034,P=0.028),and PANSS-NSS(r=-0.3487,P=0.048).However,erythrocyte membrane SFAs-PA showed positive correlation with PANSS-PSS(r=0.5844,P=0.0034)and PANSS-NSS(r=0.5380,P=0.008).In CSZ patients,plasma leptin,BMI,and erythrocyte membrane SFAs,all were significantly higher(P<0.05)compared to the CNT subjects.Plasma leptin showed positive correlation with BMI(r=0.312,P=0.032)but not with PANSS scores or erythrocyte membrane SFAs-PA.However,erythrocyte membrane SFAs-PA showed positive correlation with PANSS-NSS only(r=0.4729,P=0.031).Similar changes in the plasma leptin and erythrocyte membrane SFAs have also been reported in individuals at ultrahigh risk of developing psychosis;therefore,the above findings suggest that leptin-fatty acid biosynthesis could be disrupted before the onset of psychosis in schizophrenia.CONCLUSION Disrupted leptin-fatty acid biosynthesis/signaling could be an early manifestation of metabolic comorbidities in schizophrenia.Large-scale studies are warranted to validate the above findings.
基金supported by basic research projects of Qinghai province[2017-ZJ-770]projects of Qinghai province health and family planning commission[2017-wjzdx-38]+1 种基金the 2020"Kunlun TalentsHigh-tech Innovation and Entrepreneurial Talents"project to cultivate leading talents of Qinghai province。
文摘Kashin-Beck disease(KBD)is a chronic,endemic,degenerative osteoarthropathic condition that is predominantly found in China's Mainland.KBD is a progressive disease,and the signs and symptoms become more severe in adulthood owing to the continuous development of lesions in the joint cartilage[1].Although childhood KBD has largely been controlled,adult KBD is an important health concern in rural regions.Unfortunately,in the last century,many adult KBD patients still remain during serious epidemics.
基金supported by a grant from University of Texas Medical Branch National Institute of Environmental Health Sciences Center Pilot Project E506676
文摘Objective: The elevated incidence of obesity has been paralleled with higher risks of breast cancer. High adiposity increases leptin secretion from adipose tissue, which in turn increases cancer cell proliferation. The interplay between leptin and estrogen is one of the mechanisms through which leptin influences breast carcinogenesis. An unbalanced estrogen metabolism increases the formations of catechol estrogen quinones, DNA adducts, and cancer mutations. This study aims to investigate the effect of leptin on some estrogen metabolic enzymes and DNA adduction in breast cancer cells.Methods: High performance liquid chromatography(HPLC) was performed to analyze the DNA adducts 4-OHE1[E2]-1-N3 adenine and 4-OHE1[E2]-1-N7 guanine. Reporter gene assay, real time reverse transcription polymerase chain reaction(real time RT-PCR), and Western blot were used to assess the expression of estrogen metabolizing genes and enzymes: Cytochrome P-4501B1(CYP1B1), Nicotinamide adenine dinucleotide phosphate-quinone oxidoreductase1(NQO1), and Catechol-O-methyl transferase(COMT).Results: Leptin significantly increased the DNA adducts 4-OHE1[E2]-1-N3 adenine and 4-OHE1[E2]-1-N7 guanine.Furthermore, leptin significantly upregulated CYP1B1 promoter activity and protein expression. The luciferase promoter activities of NQO1 and m RNA levels were significantly reduced. Moreover, leptin greatly reduced the reporter activities of the COMT-P1 and COMT-P2 promoters and diminished the protein expression of COMT.Conclusions: Leptin increases DNA adduct levels in breast cancer cells partly by affecting key genes and enzymes involved in estrogen metabolism. Thus, increased focus should be directed toward leptin and its effects on the estrogen metabolic pathway as an effective approach against breast cancer.
基金financially supported by Guizhou Provincial Science and Technology Support Program[No.Qiankehe[2021]496]Science and Technology Fund of Guizhou Health Commission[No.gzwkj2021-407]+1 种基金National Major Research Project[No.2017YFC1601805]Guizhou Provincial Science and Technology Support Program[No.Qiankehe[2017]2972]。
文摘Numerous instances of poisoning caused by the ingestion of mushrooms are reported annually worldwide,with most mushroom poisoning deaths caused by the ingestion of toxic amanita fungi.Amatoxin is the main toxic component of amanita,andα-amanitin is one of the most potent toxins present in amatoxin[1].
文摘Alzheimer’s disease (AD) is the leading neurodegenerative disorder globally.Despite this,there is minimal effective therapeutics proven to reduce or prevent the progression of this disease.Glutamate is the main excitatory neurotransmitter within the central nervous system and plays a crucial role in neuronal and synaptic functions.
文摘Background: Obesity is rising globally, independent of ethnicity, race and age, and is associated with increased risk of cardiovascular mortality and morbidity especially in persons living with diabetes. The effect of adipokines such as leptin, resistin and adiponectin which are secreted by adipose tissue factors has been linked to the increased risk of the cardiovascular mortality and morbidity. Aim: This study aims to assess the levels of serum leptin and serum adiponectin in obese type 2 diabetes subjects, and their relationship with cardio-metabolic component (using lipid profile). Method: This is a cross-sectional comparative hospital-based study in which one hundred and fifty participants grouped into 60 obese, 60 non-obese none diabetic and 30 non-obese non-diabetic adults with similar age from the Endocrinology outpatient’s clinic, General outpatient department (GOPD) and staff clinic of Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC). Anthropometric parameters and other relevant clinical details of all subjects were obtained. Fasting venous blood samples were taken from all subjects for the determination of fasting plasma glucose (FPG), fasting lipid profile, glycosylated haemoglobin levels (HbA<sub>1C</sub>), fasting serum insulin, leptin, and adiponectin. Data was analysed using the Statistical Package of Social Sciences (SPSS) version 23.0. Results: Twenty-eight (46.7%)) subjects were males while 32 subjects (53.3%) were females (in obese groups). There was no statistical difference between these two groups for both sexes (p = 1.000). The age range for all subjects was 34 to 64 years with their mean age being 52 ± 7.3 years, and for type 2 subjects and the obese non-diabetic 50.7 ± 7.3 years respectively. The mean body mass index of the non-obese and non-diabetic was 23.7 ± 4 Kg/m<sup>2</sup> while the anthropometric measurements of the obese two groups were similar. The lipid profile, serum leptin and adiponectin in both the obese groups showed no difference. The relationship between components of obesity and serum leptin level in all subjects showed that serum leptin levels had significant positive correlation with BMI, WC, and serum insulin level. The correlation between adiponectin and lipid profile showed a positive correlation between serum adiponectin values and High-density lipoprotein (HDL) in obese diabetic (p = 0.02) but not in the non-diabetic group. Conclusion: In this study, there was no correlation in the serum leptin levels with the anthropometric parameters of obesity studied. For the components of the lipid profile, Triglycerides and low-density lipoprotein cholesterol (LDL) correlated with serum adiponectin and HDL showed a positive correlation with adiponectin. It is concluded that the effects of both serum adiponectin and serum leptin are driven by obesity rather than the glycaemic status of the obese subjects.