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Phone
313-577-8637
Office
iBio (Integrative Biosciences Center)
6135 Woodward, Detroit, MI 48202
Selected publications
ncbi.nlm.nih.gov/myncbi/marianna.sadagurski.1/bibliography/public
Research Description
Inflammation/Obesity/Metabolism/Aging
The prevalence of obesity in adults and children has increased globally at an alarming rate. The Sadagurski Lab employs a multi-disciplinary approach to manipulate brain neurocircuits and nutrient sensing pathways using cutting-edge molecular, genetics, and metabolic assessments in rodents to characterize developmental origins of obesity and metabolic syndrome. Through her research, Dr. Sadagurski hopes to identify new therapies to prevent and/or treat obesity and type 2 diabetes.
Early-life nutrition and inflammation
The major focus of our research is to investigate the molecular basis of the relationship between early life nutrient environment and increased risk of obesity, inflammation and diabetes. The hypothalamic appetite signaling pathways are crucial in these processes and are altered following alterations in the maternal nutritional environment in fetal and postnatal offspring. Our new data suggests that obesity and obesity-induced hypothalamic inflammation might be predisposed by maternal diet. To understand mechanisms by which early postnatal environment influences the development of obesity in adulthood, we are studying the molecular links between early-life dietary nutrition and hypothalamic inflammatory signals.
Our project investigates the influence of the early-life nutrition on hypothalamic glia cells (astrocytes and microglia), in modulating to a lasting proinflammatory profile that contributes to the development of obesity. We utilize genetically modified mice models as well as in vitro systems to study metabolic and epigenetic alterations, to identify early-life markers in hypothalamic nutrient inflammatory pathways that may contribute to the development of obesity and type 2 diabetes.
Human studies: Human blood samples are used to establish relationship between the expression pattern of inflammatory markers to the nutritional status of both mother and baby.
Aging and hypothalamic inflammation
Our data shows that aging leads to hypothalamic inflammation, but does so more slowly in mice whose lifespan has been extended by mutations that affect GH/IGF-1 signals. Specifically, early-life exposure to GH by injection, or to early-life nutrient restriction, also modulate both lifespan and the pace of hypothalamic inflammation. Our new data demonstrates that three anti-aging drugs (ACA; acarbose, 17αE2; 17-α-estradiol and NDGA; nordihydroguaiaretic acid) induce changes in hypothalamic inflammatory processes that are sexually dimorphic in a pattern that parallels the effects of these agents on mouse longevity. We are currently engaged in mechanistic testing for studying differences between male and female mice for control of aging and neuro-inflammation in old drug-treated mice. We focus on identification of molecular mechanisms that are relevant to sexual dimorphisms in glial cells to explore the potential for targeting neuro-inflammatory signals in extend longevity.
Nutrient-sensing hypothalamic pathways and metabolic dysfunction
Growth hormone (GH) signaling plays a major part in the regulation of glucose metabolism. In the brain, GH secretion contributes to rescue glucose levels in response to hypoglycemia. One intriguing populations of neurons known to have glucose lowering effects are leptin receptor (LepRb) expressing neurons. These neurons regulate metabolism (including glycemic control) and endocrine function. Our new data shows that these nutrient-sensing, LepRb neurons are crucial for the metabolic effects of hypothalamic GH signaling. Our lab is currently developing novel genetic mice models that will elucidate the involvement of specific hypothalamic neuronal circuits in the context of metabolic disorders and obesity. These studies will provide a critical insight into the brain systems that link GH/GHR axis with glucose control.
The prevalence of obesity in adults and children has increased globally at an alarming rate. The Sadagurski Lab employs a multi-disciplinary approach to manipulate brain neurocircuits and nutrient sensing pathways using cutting-edge molecular, genetics, and metabolic assessments in rodents to characterize developmental origins of obesity and metabolic syndrome. Through her research, Dr. Sadagurski hopes to identify new therapies to prevent and/or treat obesity and type 2 diabetes.
Early-life nutrition and inflammation
The major focus of our research is to investigate the molecular basis of the relationship between early life nutrient environment and increased risk of obesity, inflammation and diabetes. The hypothalamic appetite signaling pathways are crucial in these processes and are altered following alterations in the maternal nutritional environment in fetal and postnatal offspring. Our new data suggests that obesity and obesity-induced hypothalamic inflammation might be predisposed by maternal diet. To understand mechanisms by which early postnatal environment influences the development of obesity in adulthood, we are studying the molecular links between early-life dietary nutrition and hypothalamic inflammatory signals.
Our project investigates the influence of the early-life nutrition on hypothalamic glia cells (astrocytes and microglia), in modulating to a lasting proinflammatory profile that contributes to the development of obesity. We utilize genetically modified mice models as well as in vitro systems to study metabolic and epigenetic alterations, to identify early-life markers in hypothalamic nutrient inflammatory pathways that may contribute to the development of obesity and type 2 diabetes.
Human studies: Human blood samples are used to establish relationship between the expression pattern of inflammatory markers to the nutritional status of both mother and baby.
Aging and hypothalamic inflammation
Our data shows that aging leads to hypothalamic inflammation, but does so more slowly in mice whose lifespan has been extended by mutations that affect GH/IGF-1 signals. Specifically, early-life exposure to GH by injection, or to early-life nutrient restriction, also modulate both lifespan and the pace of hypothalamic inflammation. Our new data demonstrates that three anti-aging drugs (ACA; acarbose, 17αE2; 17-α-estradiol and NDGA; nordihydroguaiaretic acid) induce changes in hypothalamic inflammatory processes that are sexually dimorphic in a pattern that parallels the effects of these agents on mouse longevity. We are currently engaged in mechanistic testing for studying differences between male and female mice for control of aging and neuro-inflammation in old drug-treated mice. We focus on identification of molecular mechanisms that are relevant to sexual dimorphisms in glial cells to explore the potential for targeting neuro-inflammatory signals in extend longevity.
Nutrient-sensing hypothalamic pathways and metabolic dysfunction
Growth hormone (GH) signaling plays a major part in the regulation of glucose metabolism. In the brain, GH secretion contributes to rescue glucose levels in response to hypoglycemia. One intriguing populations of neurons known to have glucose lowering effects are leptin receptor (LepRb) expressing neurons. These neurons regulate metabolism (including glycemic control) and endocrine function. Our new data shows that these nutrient-sensing, LepRb neurons are crucial for the metabolic effects of hypothalamic GH signaling. Our lab is currently developing novel genetic mice models that will elucidate the involvement of specific hypothalamic neuronal circuits in the context of metabolic disorders and obesity. These studies will provide a critical insight into the brain systems that link GH/GHR axis with glucose control.