Background: LDL receptor-related protein-1(LRP1) is a cell-surface receptor that functions in diverse physiological pathways. We previously demonstrated that hepatocyte-specific LRP1 deficiency(hLRP1KO) promotes diet-...Background: LDL receptor-related protein-1(LRP1) is a cell-surface receptor that functions in diverse physiological pathways. We previously demonstrated that hepatocyte-specific LRP1 deficiency(hLRP1KO) promotes diet-induced insulin resistance and increases hepatic gluconeogenesis in mice. However, it remains unclear whether LRP1 regulates hepatic glycogenesis.Methods: Insulin signaling, glycogenic gene expression, and glycogen content were assessed in mice and HepG2 cells. The pcDNA 3.1 plasmid and adeno-associated virus serotype 8 vector(AAV8) were used to overexpress the truncated β-chain(βΔ) of LRP1 both in vitro and in vivo.Results: On a normal chow diet, hLRP1KO mice exhibited impaired insulin signaling and decreased glycogen content. Moreover, LRP1 expression in HepG2 cells was significantly repressed by palmitate in a dose-and time-dependent manner. Both LRP1 knockdown and palmitate treatment led to reduced phosphorylation of Akt and GSK3β, increased levels of phosphorylated glycogen synthase(GYS), and diminished glycogen synthesis in insulin-stimulated HepG2 cells, which was restored by exogenous expression of the βΔ-chain. By contrast, AAV8-mediated hepatic βΔ-chain overexpression significantly improved the insulin signaling pathway, thus activating glycogenesis and enhancing glycogen storage in the livers of high-fat diet(HFD)-fed mice.Conclusion: Our data revealed that LRP1, especially its β-chain, facilitates hepatic glycogenesis by improving the insulin signaling pathway, suggesting a new therapeutic strategy for hepatic insulin resistance-related diseases.展开更多
Objective: Aim of this study was to investigate the changes in body composition and some biochemical parameters of women at different age and body mass index (BMI) groups and to evaluate their relations with to cardio...Objective: Aim of this study was to investigate the changes in body composition and some biochemical parameters of women at different age and body mass index (BMI) groups and to evaluate their relations with to cardiometabolic risk factors. Methods: The study was created by retrospective research of the file records of total 800 women who got into nutritional counseling between 2002 - 2007 years at Cerrahpasa Medical Faculty. Participants were grouped as 10 - 19, 20 - 29, 30 - 39, 40 - 49, 50 - 59, ≥60 years according to ages and were divided into 4 groups as normal, overweight, obese and morbidly obese according to body mass index. Data were statistically analysed in SPSS for Windows computer program with ANOVA and Tukey HSD tests. Findings: There are significant differences between different age groups in weight, BMI, waist and hip circumferences, percentage of body water, fat and fat-free mass, basal metabolic rate and blood glucose, insulin, triglyceride, cholesterol, HDL, LDL levels and HOMA-IR values. HOMA-IR values were the highest at age group 1 and the lowest at age group 2. Although they were in the same BMI group;their waist circumference, basal metabolic rate and percent of body fat showed significant increases with advancing age. Conclusion: The findings of our study show that it will be useful to use standard values generated for each age group according to BMI levels in predicting increased cardiovascular and metabolic risks together with advancing age. While the lowest rate of obesity according to body fat percent (>30%) was found at the ages in between 20 - 29 (58.4%), it is noteworthy that the obesity rate with respect to their body fat percent has been noticed at the ages of 10 to 19 (2.3%). Comparing with the other groups, significantly higher body heights found at the ages in between 10 - 19, could possibly predicate that the new generations are having better nutrition and overhaul. On the other hand, it was known that as a result of eating bugs and/or over-nutrition, besides insertion of inactive life style, children have become more sensitive to obesity and related health problems. As seen in our study, the healthiest values are at the ages in between 20 - 29, the results were commentated as the women at those ages are showing more interest in their physical appearance and their health. In accordance with our study’s data, in order to cope with obesity and related illnesses, which are having an importance in public health, we concluded that generalizing continuous and effective trainings on nutrition concerning families even the educators starting from the childhood, can be usefull.展开更多
基金financially supported by the National Natural Science Foundation of China (Grant No. 82270854)the Natural Science Foundation of Chongqing+2 种基金China (No. cstc2020jcyj-msxm X0408)the Program for Youth Innovation in Future MedicineChongqing Medical University (No. W0162) to Yinyuan Ding。
文摘Background: LDL receptor-related protein-1(LRP1) is a cell-surface receptor that functions in diverse physiological pathways. We previously demonstrated that hepatocyte-specific LRP1 deficiency(hLRP1KO) promotes diet-induced insulin resistance and increases hepatic gluconeogenesis in mice. However, it remains unclear whether LRP1 regulates hepatic glycogenesis.Methods: Insulin signaling, glycogenic gene expression, and glycogen content were assessed in mice and HepG2 cells. The pcDNA 3.1 plasmid and adeno-associated virus serotype 8 vector(AAV8) were used to overexpress the truncated β-chain(βΔ) of LRP1 both in vitro and in vivo.Results: On a normal chow diet, hLRP1KO mice exhibited impaired insulin signaling and decreased glycogen content. Moreover, LRP1 expression in HepG2 cells was significantly repressed by palmitate in a dose-and time-dependent manner. Both LRP1 knockdown and palmitate treatment led to reduced phosphorylation of Akt and GSK3β, increased levels of phosphorylated glycogen synthase(GYS), and diminished glycogen synthesis in insulin-stimulated HepG2 cells, which was restored by exogenous expression of the βΔ-chain. By contrast, AAV8-mediated hepatic βΔ-chain overexpression significantly improved the insulin signaling pathway, thus activating glycogenesis and enhancing glycogen storage in the livers of high-fat diet(HFD)-fed mice.Conclusion: Our data revealed that LRP1, especially its β-chain, facilitates hepatic glycogenesis by improving the insulin signaling pathway, suggesting a new therapeutic strategy for hepatic insulin resistance-related diseases.
文摘Objective: Aim of this study was to investigate the changes in body composition and some biochemical parameters of women at different age and body mass index (BMI) groups and to evaluate their relations with to cardiometabolic risk factors. Methods: The study was created by retrospective research of the file records of total 800 women who got into nutritional counseling between 2002 - 2007 years at Cerrahpasa Medical Faculty. Participants were grouped as 10 - 19, 20 - 29, 30 - 39, 40 - 49, 50 - 59, ≥60 years according to ages and were divided into 4 groups as normal, overweight, obese and morbidly obese according to body mass index. Data were statistically analysed in SPSS for Windows computer program with ANOVA and Tukey HSD tests. Findings: There are significant differences between different age groups in weight, BMI, waist and hip circumferences, percentage of body water, fat and fat-free mass, basal metabolic rate and blood glucose, insulin, triglyceride, cholesterol, HDL, LDL levels and HOMA-IR values. HOMA-IR values were the highest at age group 1 and the lowest at age group 2. Although they were in the same BMI group;their waist circumference, basal metabolic rate and percent of body fat showed significant increases with advancing age. Conclusion: The findings of our study show that it will be useful to use standard values generated for each age group according to BMI levels in predicting increased cardiovascular and metabolic risks together with advancing age. While the lowest rate of obesity according to body fat percent (>30%) was found at the ages in between 20 - 29 (58.4%), it is noteworthy that the obesity rate with respect to their body fat percent has been noticed at the ages of 10 to 19 (2.3%). Comparing with the other groups, significantly higher body heights found at the ages in between 10 - 19, could possibly predicate that the new generations are having better nutrition and overhaul. On the other hand, it was known that as a result of eating bugs and/or over-nutrition, besides insertion of inactive life style, children have become more sensitive to obesity and related health problems. As seen in our study, the healthiest values are at the ages in between 20 - 29, the results were commentated as the women at those ages are showing more interest in their physical appearance and their health. In accordance with our study’s data, in order to cope with obesity and related illnesses, which are having an importance in public health, we concluded that generalizing continuous and effective trainings on nutrition concerning families even the educators starting from the childhood, can be usefull.
