Obesity and diabetes mellitus are common metabolic diseases prevalent worldwide.Mice are commonly used to study the pathogenesis of these two conditions.Obesity and diabetes mellitus are induced by administering a hig...Obesity and diabetes mellitus are common metabolic diseases prevalent worldwide.Mice are commonly used to study the pathogenesis of these two conditions.Obesity and diabetes mellitus are induced by administering a high-fat diet in many studies although other diet-induced models are also used.Several factors may influence the outcome of the studies done to study diet-induced obesity in mice.The immune system plays a crucial role in the susceptibility of mice to develop obesity and metabolic disease.In this article,the reasons for differences in susceptibility to develop obesity and diabetes mellitus in mice in response to high-fat-diet feeding and the influence of immunological bias of the mice strain used in studies are evaluated.Mice strains that induce proinflammatory and Th1-type immune responses are found to be susceptible to high-fat-diet-induced obesity.A few studies which directly compared the effect of a high-fat diet on obesity and diabetic phenotype in Th1-and Th2-biased mice strains were briefly analyzed.Based on the observations,it is proposed that the liver and adipose tissue may respond differently to high-fat-diet feeding regimens in Th1-and Th2-biased mice strains.For instance,in Th1-biased mice,adipose tissue fat content was high both in the baseline as well as in response to a high-fat diet whereas in the liver,it was found to be less.It can be inferred that the immune responses to diet-induced models may provide insights into the pathogenesis of obesity and diabetes mellitus.展开更多
In early life, the immune system plays an essential role in brain development. In our study, the immunopotentiator thymosin alpha-1(Ta1) was peripherally administered to neonatal mice to explore whether the peripher...In early life, the immune system plays an essential role in brain development. In our study, the immunopotentiator thymosin alpha-1(Ta1) was peripherally administered to neonatal mice to explore whether the peripheral immunopotentiator affects neurodevelopment and cognition, and to further investigate the relevant mechanism. Compared with the control group, the Ta1 mice displayed better cognitive abilities in early life. The numbers of 5-bromodeoxyuridine(Brd U)+, nestin+,T-box transcription factor 2(Tbr2)+, Brd U+/doublecortin(DCX)+, Brd U+/ionized calcium-binding adaptor molecule 1(Iba1)+, and Brd U+/neuronal nuclei(Neu N)+ cells in the hippocampus were increased in the Ta1 group,accompanied by increased interleukin-4(IL-4), interferon-gamma, brain-derived neurotrophic factor, nerve growth factor, and insulin-like growth factor-1 as well as decreased IL-6 and tumor necrosis factor-a. Furthermore, the Ta1-group showed a Th1-polarized immune response, and the neurotrophic factors were positively associated with the Th1/Th2 ratio. More importantly, administration of Ta1 blocked lipopolysaccharide-induced impairment of hippocampal neurogenesis in early life. These findings suggest that peripheral Ta1 contributes to neurogenesis and cognition probably through a systemic Th1 bias, as well as neuroprotection against LPS infection by Ta1.展开更多
文摘Obesity and diabetes mellitus are common metabolic diseases prevalent worldwide.Mice are commonly used to study the pathogenesis of these two conditions.Obesity and diabetes mellitus are induced by administering a high-fat diet in many studies although other diet-induced models are also used.Several factors may influence the outcome of the studies done to study diet-induced obesity in mice.The immune system plays a crucial role in the susceptibility of mice to develop obesity and metabolic disease.In this article,the reasons for differences in susceptibility to develop obesity and diabetes mellitus in mice in response to high-fat-diet feeding and the influence of immunological bias of the mice strain used in studies are evaluated.Mice strains that induce proinflammatory and Th1-type immune responses are found to be susceptible to high-fat-diet-induced obesity.A few studies which directly compared the effect of a high-fat diet on obesity and diabetic phenotype in Th1-and Th2-biased mice strains were briefly analyzed.Based on the observations,it is proposed that the liver and adipose tissue may respond differently to high-fat-diet feeding regimens in Th1-and Th2-biased mice strains.For instance,in Th1-biased mice,adipose tissue fat content was high both in the baseline as well as in response to a high-fat diet whereas in the liver,it was found to be less.It can be inferred that the immune responses to diet-induced models may provide insights into the pathogenesis of obesity and diabetes mellitus.
基金supported by the Natural Science Foundation of Guangdong Province, China (2014A030310343, 2015A030313153, and 2016A030313253)the Medical Scientific Research Foundation of Guangdong Province, China (A2015382)the Doctoral Program of Guangzhou Medical University, China (2014C19)
文摘In early life, the immune system plays an essential role in brain development. In our study, the immunopotentiator thymosin alpha-1(Ta1) was peripherally administered to neonatal mice to explore whether the peripheral immunopotentiator affects neurodevelopment and cognition, and to further investigate the relevant mechanism. Compared with the control group, the Ta1 mice displayed better cognitive abilities in early life. The numbers of 5-bromodeoxyuridine(Brd U)+, nestin+,T-box transcription factor 2(Tbr2)+, Brd U+/doublecortin(DCX)+, Brd U+/ionized calcium-binding adaptor molecule 1(Iba1)+, and Brd U+/neuronal nuclei(Neu N)+ cells in the hippocampus were increased in the Ta1 group,accompanied by increased interleukin-4(IL-4), interferon-gamma, brain-derived neurotrophic factor, nerve growth factor, and insulin-like growth factor-1 as well as decreased IL-6 and tumor necrosis factor-a. Furthermore, the Ta1-group showed a Th1-polarized immune response, and the neurotrophic factors were positively associated with the Th1/Th2 ratio. More importantly, administration of Ta1 blocked lipopolysaccharide-induced impairment of hippocampal neurogenesis in early life. These findings suggest that peripheral Ta1 contributes to neurogenesis and cognition probably through a systemic Th1 bias, as well as neuroprotection against LPS infection by Ta1.