Yong Joo Ahn (United States of America)
Wake Forest School of Medicine Molecular MedicineAuthor Of 1 Presentation
O050 - Glutaredoxin 1 Controls the Sexual Dimorphic Reprogramming of Monocytes by Nutrient Stress and Protects Mice Against Obesity and Atherosclerosis (ID 1213)
Abstract
Background and Aims
The aim of this study is to investigate the role of Grx1 in the onset of nutrient-stress induced obesity and atherosclerosis.
Methods
Age and sex-matched male and female Grx1-/- and WT mice were a fed chow diet for 18 months. Body weights and fasting blood glucose levels were measured weekly, and atherosclerosis was accessed after 18 months. Myeloid Grx1 deficient mice (Grx1Leuko-/-) were generated by transplanting either WT or Grx1-/- bone marrow (BM) cells into atherosclerosis-prone male and female LDLR-/- mice and were fed a high-calorie diet (HCD) for 20 weeks. Monocyte priming was determined by in vivo Matrigel plug assay. MKP-1 activity was measured to examine monocyte function. Macrophage reprogramming was determined by targeted RT-qPCR using custom-designed 384 TaqMan® Gene Expression Array Cards.
Results
At 18 months of age, female Grx1-/- mice were 30% heavier than males. Monocytes in 18-month old female Grx1-/- mice were primed, and promoted the recruitment of monocyte-derived macrophages into adipose tissues, and developed early atherosclerotic lesions. Grx1 deficiency promotes the reprogramming of macrophages, notable induction of genes encoding ROS and RNS generating enzymes. This reprogramming is sexually dimorphic and dramatically exacerbated in macrophages from old female mice. Female but not male Grx1Leuko-/- mice recapitulated the obesogenic and atherogenic phenotype of female Grx1-/- mice, showing accelerated weight gain (+14.6%), hyperglycemia, and accelerated atherosclerosis (+21%) compared to WT BM recipient mice.
Conclusions
We identified a critical and sexually dimorphic role for monocytic Grx1 activity in protecting monocytes and macrophages from HFD-induced reprogramming and dysfunction and preventing obesity and atherosclerosis.
Presenter of 1 Presentation
O050 - Glutaredoxin 1 Controls the Sexual Dimorphic Reprogramming of Monocytes by Nutrient Stress and Protects Mice Against Obesity and Atherosclerosis (ID 1213)
Abstract
Background and Aims
The aim of this study is to investigate the role of Grx1 in the onset of nutrient-stress induced obesity and atherosclerosis.
Methods
Age and sex-matched male and female Grx1-/- and WT mice were a fed chow diet for 18 months. Body weights and fasting blood glucose levels were measured weekly, and atherosclerosis was accessed after 18 months. Myeloid Grx1 deficient mice (Grx1Leuko-/-) were generated by transplanting either WT or Grx1-/- bone marrow (BM) cells into atherosclerosis-prone male and female LDLR-/- mice and were fed a high-calorie diet (HCD) for 20 weeks. Monocyte priming was determined by in vivo Matrigel plug assay. MKP-1 activity was measured to examine monocyte function. Macrophage reprogramming was determined by targeted RT-qPCR using custom-designed 384 TaqMan® Gene Expression Array Cards.
Results
At 18 months of age, female Grx1-/- mice were 30% heavier than males. Monocytes in 18-month old female Grx1-/- mice were primed, and promoted the recruitment of monocyte-derived macrophages into adipose tissues, and developed early atherosclerotic lesions. Grx1 deficiency promotes the reprogramming of macrophages, notable induction of genes encoding ROS and RNS generating enzymes. This reprogramming is sexually dimorphic and dramatically exacerbated in macrophages from old female mice. Female but not male Grx1Leuko-/- mice recapitulated the obesogenic and atherogenic phenotype of female Grx1-/- mice, showing accelerated weight gain (+14.6%), hyperglycemia, and accelerated atherosclerosis (+21%) compared to WT BM recipient mice.
Conclusions
We identified a critical and sexually dimorphic role for monocytic Grx1 activity in protecting monocytes and macrophages from HFD-induced reprogramming and dysfunction and preventing obesity and atherosclerosis.