Background: Host genetic background and sex, play central roles in defining the pathogenesis of type 2 diabetes(T2 D), obesity and infectious diseases. Our previous studies demonstrated the utilization of genetically ...Background: Host genetic background and sex, play central roles in defining the pathogenesis of type 2 diabetes(T2 D), obesity and infectious diseases. Our previous studies demonstrated the utilization of genetically highly diverse inbred mouse lines, namely collaborative cross(CC), for dissecting host susceptibility for the development of T2 D and obesity, showing significant variations following high-fat(42% fat) diet(HFD). Here, we aimed to assessing the host genetic background and sex effects on T2 D and obesity development in response to oral-mixed bacterial infection and HFD using the CC lines.Materials and Methods: Study cohort consists of 97 mice from 2 CC lines(both sexes), maintained on either HFD or Standard diet(CHD) for 12 weeks. At week 5 a group of mice from each diet were infected with Porphyromonas gingivalis(Pg) and Fusobacterium nucleatum(Fn) bacteria(control groups without infection). Body weight(BW) and glucose tolerance ability were assessed at the end time point of the experiment.Results: The CC lines varied(P <.05) at their BW gain and glucose tolerance ability(with sex effect) in response to diets and/or infection, showing opposite responses despite sharing the same environmental conditions. The combination of diet and infection enhances BW accumulation for IL1912, while restraints it for IL72. As for glucose tolerance ability, only females(both lines) were deteriorated in response to infection.Conclusions: This study emphasizes the power of the CC mouse population for the characterization of host genetic makeup for defining the susceptibility of the individual to development of obesity and/or impaired glucose tolerance.展开更多
Background:Type 2 diabetes(T2D)is a polygenic metabolic disease,character-ized by high fasting blood glucose(FBG).The ability of cranberry(CRN)fruit to regulate glycemia in T2D patients is well known.Here,a cohort of ...Background:Type 2 diabetes(T2D)is a polygenic metabolic disease,character-ized by high fasting blood glucose(FBG).The ability of cranberry(CRN)fruit to regulate glycemia in T2D patients is well known.Here,a cohort of 13 lines of the genetically diverse Collaborative Cross(CC)mouse model was assessed for the effect of non-dialyzable material(NDM)of cranberry extract in lowering fasting blood glucose.Methods:Eight-week-old mice were maintained on either a standard chow diet(con-trol group)or a high-fat diet(HFD)for 12 weeks,followed by injections of intraperi-toneal(IP)NDM(50 mg/kg)per mouse,three times a week for the next 6 weeks.Absolute FBG(mg/dl)was measured bi-weekly and percentage changes in FBG(%FBG)between weeks 0 and 12 were calculated.Results:Statistical analysis showed a significant decrease in FBG between weeks 0 and 12 in male and female mice maintained on CHD.However,a non-significant in-crease in FBG values was observed in male and female mice maintained on HFD dur-ing the same period.Following administration of NDM during the following 6 weeks,the results show a variation in significant levels of FBG lowering between lines,male and female mice and under the different diets.Conclusion:The results suggest that the efficacy of NDM treatment in lowering FGB depends on host genetic background(pharmacogenetics),sex of the mouse(phar-macosex),and diet(pharmacodiet).All these results support the need for follow-up research to better understand and implement a personalized medicine approach/uti-lization of NDM for reducing FBG.展开更多
Diets these days contain more fats. High fat diet (HFD) is a model of unhealthy eating in experimental animals. It is known to induce inflammatory responses and oxidative stress. Cannabidiol (CBD), the non-psychoactiv...Diets these days contain more fats. High fat diet (HFD) is a model of unhealthy eating in experimental animals. It is known to induce inflammatory responses and oxidative stress. Cannabidiol (CBD), the non-psychoactive component of Cannbis sativa has been legalized for medicinal use in many countries of the world. Omega 3 fatty acid, commonly found in fish oil is medicinal and necessary for brain development. The antioxidant and neuroprotective functions of CBD and omega 3 have made them relevant in many researches. In this study, 45 mice were used and divided into three groups of 15 animals each: Group 1 (normal feed and water ad libidum);Group 2 (HFD ad libidum);Group 3 (HFD + CBD + Omega 3) for 16 weeks. Thereafter, five animals from each group were selected and their frontal lobes were harvested for histological analyses using H and E staining. The remaining mice were allowed to feed on normal diet and observed till death. At the end, HFD significantly reduced life span (57.4 ± 0.3) when compared to control (78.9 ± 1.6) and HFD + CBD + omega 3 group (74.5 ± 0.8) at p < 0.05. HFD also caused significant brain ischemic damage, neuronophagia and significant perivascular oedema. CBD + Omega 3 induced significant astrocytosis compared to control and HFD group. The immune stimulation by the CBD + Omega 3 could be responsible for tissue survival and longevity by protection from inflammatory and oxidative injuries. Ischaemic tissue death could have been prevented by amelioration of artheroma formation due to HFD. Further studies will be required to ascertain other possible mechanisms behind these findings.展开更多
Chronic intake of High Fat Diet (HFD) has the potential of causing a number of metabolic disorders. It is also theorized to be involved in perturbation of gut microbiota. Cannabididol (CBD) and omega 3 are known to po...Chronic intake of High Fat Diet (HFD) has the potential of causing a number of metabolic disorders. It is also theorized to be involved in perturbation of gut microbiota. Cannabididol (CBD) and omega 3 are known to possess a number of medicinal usefulness. Their combined use in experimental interventions is quite limited. A total of 15 mice were used for this research divided into three groups of five animals each. Group 1 was administered water and normal chow ad libidum. Group 2 had HFD and water ad libidum. Group 3 had HFD plus CBD (10 mg/kg) and omega 3 (200 mg/kg) all for a total of 12 weeks. They were tested on the elevated plus maze (EPM) and average entry time into the closed arm was recorded. They were also tested on the Y-maze and spontaneous alternations were measured. Thereafter animals were sacrificed and faecal content in the caecum was collected in sterile bottles and cultured for E. coli count. It was found that HFD group at p value E. coli count (2.4 × 10<sup>6</sup> ± 4.5) compared to group 1 (1.4 × 10<sup>6</sup> ± 5.6) and group 3 (1.42 × 10<sup>6</sup> ± 6.3). The findings revealed that HFD enhanced gut E. coli overgrowth which was reduced by CBD and Omega 3. The memory impairment and anxiety induction by HFD was also significantly ameliorated by CBD and omega 3. E. coli known to be implicated in dementia induction was suppressed by the interventions. Possible mechanisms proposed are actions of CBD and omega 3 on CB1, TRVP and 5HT receptors in reducing anxiety and their antioxidant/anti-inflammatory actions in mitigating the neuro-inflammatory effect of HFD and immune hyperstimulation of E. coli via the gutbrain-axis.展开更多
基金Israeli Science Foundation (ISF),Grant/Award Number 1085/18German Israeli Science Foundation (GIF),Grant/Award Number I-63-410.20-2017+1 种基金Binational Science Foundation (BSF),Grant/Award Number 2015077Tel-Aviv University
文摘Background: Host genetic background and sex, play central roles in defining the pathogenesis of type 2 diabetes(T2 D), obesity and infectious diseases. Our previous studies demonstrated the utilization of genetically highly diverse inbred mouse lines, namely collaborative cross(CC), for dissecting host susceptibility for the development of T2 D and obesity, showing significant variations following high-fat(42% fat) diet(HFD). Here, we aimed to assessing the host genetic background and sex effects on T2 D and obesity development in response to oral-mixed bacterial infection and HFD using the CC lines.Materials and Methods: Study cohort consists of 97 mice from 2 CC lines(both sexes), maintained on either HFD or Standard diet(CHD) for 12 weeks. At week 5 a group of mice from each diet were infected with Porphyromonas gingivalis(Pg) and Fusobacterium nucleatum(Fn) bacteria(control groups without infection). Body weight(BW) and glucose tolerance ability were assessed at the end time point of the experiment.Results: The CC lines varied(P <.05) at their BW gain and glucose tolerance ability(with sex effect) in response to diets and/or infection, showing opposite responses despite sharing the same environmental conditions. The combination of diet and infection enhances BW accumulation for IL1912, while restraints it for IL72. As for glucose tolerance ability, only females(both lines) were deteriorated in response to infection.Conclusions: This study emphasizes the power of the CC mouse population for the characterization of host genetic makeup for defining the susceptibility of the individual to development of obesity and/or impaired glucose tolerance.
基金supported by a core fund from Tel-Aviv University.
文摘Background:Type 2 diabetes(T2D)is a polygenic metabolic disease,character-ized by high fasting blood glucose(FBG).The ability of cranberry(CRN)fruit to regulate glycemia in T2D patients is well known.Here,a cohort of 13 lines of the genetically diverse Collaborative Cross(CC)mouse model was assessed for the effect of non-dialyzable material(NDM)of cranberry extract in lowering fasting blood glucose.Methods:Eight-week-old mice were maintained on either a standard chow diet(con-trol group)or a high-fat diet(HFD)for 12 weeks,followed by injections of intraperi-toneal(IP)NDM(50 mg/kg)per mouse,three times a week for the next 6 weeks.Absolute FBG(mg/dl)was measured bi-weekly and percentage changes in FBG(%FBG)between weeks 0 and 12 were calculated.Results:Statistical analysis showed a significant decrease in FBG between weeks 0 and 12 in male and female mice maintained on CHD.However,a non-significant in-crease in FBG values was observed in male and female mice maintained on HFD dur-ing the same period.Following administration of NDM during the following 6 weeks,the results show a variation in significant levels of FBG lowering between lines,male and female mice and under the different diets.Conclusion:The results suggest that the efficacy of NDM treatment in lowering FGB depends on host genetic background(pharmacogenetics),sex of the mouse(phar-macosex),and diet(pharmacodiet).All these results support the need for follow-up research to better understand and implement a personalized medicine approach/uti-lization of NDM for reducing FBG.
文摘Diets these days contain more fats. High fat diet (HFD) is a model of unhealthy eating in experimental animals. It is known to induce inflammatory responses and oxidative stress. Cannabidiol (CBD), the non-psychoactive component of Cannbis sativa has been legalized for medicinal use in many countries of the world. Omega 3 fatty acid, commonly found in fish oil is medicinal and necessary for brain development. The antioxidant and neuroprotective functions of CBD and omega 3 have made them relevant in many researches. In this study, 45 mice were used and divided into three groups of 15 animals each: Group 1 (normal feed and water ad libidum);Group 2 (HFD ad libidum);Group 3 (HFD + CBD + Omega 3) for 16 weeks. Thereafter, five animals from each group were selected and their frontal lobes were harvested for histological analyses using H and E staining. The remaining mice were allowed to feed on normal diet and observed till death. At the end, HFD significantly reduced life span (57.4 ± 0.3) when compared to control (78.9 ± 1.6) and HFD + CBD + omega 3 group (74.5 ± 0.8) at p < 0.05. HFD also caused significant brain ischemic damage, neuronophagia and significant perivascular oedema. CBD + Omega 3 induced significant astrocytosis compared to control and HFD group. The immune stimulation by the CBD + Omega 3 could be responsible for tissue survival and longevity by protection from inflammatory and oxidative injuries. Ischaemic tissue death could have been prevented by amelioration of artheroma formation due to HFD. Further studies will be required to ascertain other possible mechanisms behind these findings.
文摘Chronic intake of High Fat Diet (HFD) has the potential of causing a number of metabolic disorders. It is also theorized to be involved in perturbation of gut microbiota. Cannabididol (CBD) and omega 3 are known to possess a number of medicinal usefulness. Their combined use in experimental interventions is quite limited. A total of 15 mice were used for this research divided into three groups of five animals each. Group 1 was administered water and normal chow ad libidum. Group 2 had HFD and water ad libidum. Group 3 had HFD plus CBD (10 mg/kg) and omega 3 (200 mg/kg) all for a total of 12 weeks. They were tested on the elevated plus maze (EPM) and average entry time into the closed arm was recorded. They were also tested on the Y-maze and spontaneous alternations were measured. Thereafter animals were sacrificed and faecal content in the caecum was collected in sterile bottles and cultured for E. coli count. It was found that HFD group at p value E. coli count (2.4 × 10<sup>6</sup> ± 4.5) compared to group 1 (1.4 × 10<sup>6</sup> ± 5.6) and group 3 (1.42 × 10<sup>6</sup> ± 6.3). The findings revealed that HFD enhanced gut E. coli overgrowth which was reduced by CBD and Omega 3. The memory impairment and anxiety induction by HFD was also significantly ameliorated by CBD and omega 3. E. coli known to be implicated in dementia induction was suppressed by the interventions. Possible mechanisms proposed are actions of CBD and omega 3 on CB1, TRVP and 5HT receptors in reducing anxiety and their antioxidant/anti-inflammatory actions in mitigating the neuro-inflammatory effect of HFD and immune hyperstimulation of E. coli via the gutbrain-axis.
