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Nutritional and Metabolic Diseases Commons™
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Articles 1 - 12 of 12
Full-Text Articles in Nutritional and Metabolic Diseases
Sex-Specific Roles Of The Adipocyte Mineralocorticoid Receptor In Obesity And Early Life Stress, Meghan B. Turner
Sex-Specific Roles Of The Adipocyte Mineralocorticoid Receptor In Obesity And Early Life Stress, Meghan B. Turner
Theses and Dissertations--Pharmacology and Nutritional Sciences
Obesity is a burgeoning health epidemic caused by chronic overnutrition and exacerbated by genetic, environmental and developmental factors. The adipocyte mineralocorticoid receptor (MR), a transcriptionally active nuclear receptor, is speculated to contribute to metabolic dysfunction in the obese state. MR expression is increased in obese adipose tissue, and MR modulates the expression of fat-derived hormones such as leptin and adiponectin. In women, obesity can be exacerbated by early life stress, such as adverse childhood experiences (ACEs). Studies show that women display a positive association between cumulative ACE exposures and increased body mass index. Previously, we demonstrated that maternal separation and …
Long-Term Cardiometabolic Effects Of Preconceptional And Prenatal Opioid Exposure In The Adult Offspring, Nermin Hassan Mohamed Selim Ahmed
Long-Term Cardiometabolic Effects Of Preconceptional And Prenatal Opioid Exposure In The Adult Offspring, Nermin Hassan Mohamed Selim Ahmed
Theses and Dissertations--Pharmacology and Nutritional Sciences
Opioid use disorder (OUD), one of the greatest public health threats in the US, requires urgent attention. In 2022, the CDC reported 107,941 overdose deaths, over 70% attributed to synthetic opioids such as fentanyl (FEN). An alarming increase in opioid use disorder (OUD) diagnoses in pregnant people resulted in a 5-fold rise in cases of neonatal opioid withdrawal syndrome (NOWS). This condition elicits sympathetic overactivity, neural hyperexcitability, and a stress reaction characterized by tachycardia and hypertension. Whether prenatal exposure to fentanyl induces cardiovascular dysfunction in the offspring remains undetermined, impeding the timely development of strategies to mitigate OUD-related health risks …
The Function Of The Insulin Receptor In Liver Subcell Types And Its Dichotomous Role In Hepatic Dysfunction, Wang-Hsin Lee
The Function Of The Insulin Receptor In Liver Subcell Types And Its Dichotomous Role In Hepatic Dysfunction, Wang-Hsin Lee
Theses and Dissertations--Pharmacology and Nutritional Sciences
Insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD) have become significant health issues worldwide. Increased prevalence of hepatic insulin resistance and MASLD worsens the threat of its progressive complications, such as liver fibrosis, which can lead to cirrhosis and death if left untreated. Treatments for MASLD-induced liver fibrosis are mainly insulin sensitizers. However, activating insulin signaling leads to a higher death rate in end-stage liver fibrosis. This dissertation discusses the emerging insights into hepatic insulin resistance and potential treatment targets in the heme degradation pathway for reversal. We also investigated the mechanisms that the insulin receptor (INSR) regulates in …
Exenatide As Chronopharmacotherapy For T2dm Associated Complications: Targeting Nondipping Blood Pressure And Sleep Insufficiency, Aaron Chacon
Theses and Dissertations--Pharmacology and Nutritional Sciences
Although largely impacted by age, race and ethnicity, and socioeconomic factors, Type 2 Diabetes Mellitus (T2DM) is primarily driven by obesity, currently affecting ~30 million in the U.S and ~463 million globally. T2DM carries numerous complications, including high prevalence of hypertension and nondipping blood pressure (BP), sleep insufficiency and fragmentation. Nondipping BP is an inadequate drop in BP (≤ 10%) during sleeping hours compared with waking hours. Lending to this, sleep disturbance acts as both precursor and consequence of metabolic dysregulation, greatly impacting circadian rhythmicity. To model these conditions, we utilized diabetic (db/db) mice. These mice carry a point mutation …
The Gestation Of Health: Environmental Insults, Behavioral Interventions, And Protective Mechanisms, Brittany Breon Rice
The Gestation Of Health: Environmental Insults, Behavioral Interventions, And Protective Mechanisms, Brittany Breon Rice
Theses and Dissertations--Pharmacology and Nutritional Sciences
Diabetes remains a leading cause of death nationwide despite pharmacological advances. Recent etiological investigations of the disease detail the role of perinatal exposure to environmental contaminants, such as polychlorinated biphenyls (PCBs), in enhancing disease susceptibility. Polychlorinated biphenyl 126, a coplanar PCB, elicits its toxic effects through the aryl-hydrocarbon receptor and the disruption of endocrine signaling. The goal of this dissertation was to focus on delineating the differences in the developmental windows of diabetes susceptibility respective to the timing of PCB126 exposure and to understand the influence of maternal exercise and nuclear-factor erythroid-2-related factor 2 (Nrf2) expression in combating the negative …
Role Of Pancreatic Amylin In Alzheimer’S And Brain Microvascular Pathologies, Han Gia Ly
Role Of Pancreatic Amylin In Alzheimer’S And Brain Microvascular Pathologies, Han Gia Ly
Theses and Dissertations--Pharmacology and Nutritional Sciences
Alzheimer disease (AD) and cerebral vascular disease (CVD) are common causes of impaired cognition and behavior in humans. Epidemiological studies have shown that AD and CVD development and progression associated with metabolic risk factors including type 2 diabetes (T2D). However, the underlying molecular mechanisms remain elusive, which hampers the development of treatment and prevention strategies. Research results from our laboratory and others have shown that amylin, a hormone secreted by the pancreas and involved in glucose homeostasis, induces small-vessel-type pathologies and modulates amyloid composition in both familial (genetically predisposed) and sporadic forms of AD. The results indicate amylin as a …
Pyocyanin, A Virulence Factor Produced By Sepsis-Causing Pseudomonas Aeruginosa, Promotes Adipose Wasting And Cachexia, Nika Larian
Theses and Dissertations--Pharmacology and Nutritional Sciences
Sepsis is a leading cause of death among critically ill patients that results in metabolic alterations including hypercatabolism, lipoatrophy, and muscle wasting, contributing to the development of cachexia. Septic cachexia is associated with loss of body weight, fat mass, and lean mass and dysregulated immune function. There are currently no efficacious treatment strategies for septic cachexia, and nutritional interventions have limited success in preventing hypercatabolic wasting. Pyocyanin is a virulence factor produced by sepsis-causing Pseudomonas aeruginosa that has been shown to activate the aryl hydrocarbon receptor (AhR), increase inflammation, and produce reactive oxygen species. Thus, pyocyanin represents a novel mechanistic …
Mechanisms And Potential Therapy On Disrupted Blood Pressure Circadian Rhythm In Diabetes, Tianfei Hou
Mechanisms And Potential Therapy On Disrupted Blood Pressure Circadian Rhythm In Diabetes, Tianfei Hou
Theses and Dissertations--Pharmacology and Nutritional Sciences
Arterial blood pressure (BP) undergoes a 24-hour oscillation that peaks in the active day and reaches a nadir at night during sleep in humans. Reduced nocturnal BP fall (also known as non-dipper) is the most common disruption of BP circadian rhythm and is associated with increased risk of untoward cardiovascular events and target organ injury. Up to 75% of diabetic patients are non-dippers. However, the mechanisms underlying diabetes associated non-dipping BP are largely unknown. To address this important question, we generated a novel diabetic db/db-mPer2Luc mouse model (db/db-mPer2Luc) that allows quantitatively measuring of mPER2 protein oscillation …
The Role Of Progesterone Receptor Membrane Component 1 In Receptor Trafficking And Disease, Kaia K. Hampton
The Role Of Progesterone Receptor Membrane Component 1 In Receptor Trafficking And Disease, Kaia K. Hampton
Theses and Dissertations--Pharmacology and Nutritional Sciences
The progesterone receptor membrane component 1 (PGRMC1) is a multifunctional protein with a heme-binding domain that promotes cellular signaling via receptor trafficking, and is essential for some elements of tumor growth and metastasis. PGRMC1 is upregulated in breast, colon, lung and thyroid tumors. We expanded the analysis of PGRMC1 in the clinical setting, and report the first analysis of PGRMC1 in human oral cavity and ovarian tumors and found PGRMC1 to correlate with lung and ovarian cancer patient survival. Furthermore, we discovered a specific role for PGRMC1 in cancer stem cell viability. PGRMC1 directly associates with the epidermal growth factor …
The Role Of Pxr And Ikkβ Signaling In Cardiometabolic Disease, Robert N. Helsley
The Role Of Pxr And Ikkβ Signaling In Cardiometabolic Disease, Robert N. Helsley
Theses and Dissertations--Pharmacology and Nutritional Sciences
Cardiovascular disease (CVD) is the leading cause of death worldwide and is partially attributed to perturbations in lipid metabolism. Xenobiotics, such as pharmaceutical drugs and environmental chemicals, have been associated with increased risk of CVD in multiple large-scale human population studies, but the underlying mechanisms remain poorly defined. We and others have identified several xenobiotics as potent agonists for the pregnane X receptor (PXR), a nuclear receptor that can be activated by numerous drugs as well as environmental and dietary chemicals. However, the role of PXR in mediating the pathophysiological effects of xenobiotic exposure in humans and animals remains elusive. …
Regulation Of Pancreatic Β-Cell Function By The Renin-Angiotensin System In Type 2 Diabetes, Robin C. Shoemaker
Regulation Of Pancreatic Β-Cell Function By The Renin-Angiotensin System In Type 2 Diabetes, Robin C. Shoemaker
Theses and Dissertations--Pharmacology and Nutritional Sciences
Diet-induced obesity promotes type 2 diabetes (T2D). Drugs that inhibit the renin-angiotensin system (RAS) have been demonstrated in clinical trials to decrease the onset of T2D. Previously, we demonstrated that mice made obese from chronic consumption of a high-fat (HF) diet have marked elevations in systemic concentrations of angiotensin II (AngII). Pancreatic islets have been reported to possess components of the renin-angiotensin system (RAS), including angiotensin type 1a receptors (AT1aR), the primary receptor for AngII, and angiotensin converting-enzyme 2 (ACE2), which negatively regulates the RAS by catabolizing AngII to angiotensin-(1-7) (Ang-(1-7)). These two opposing proteins have been implicated in the …
Impact Of Positive And Negative Health Behaviors On Female Mice And/Or Their Offspring, Kristen M. Platt
Impact Of Positive And Negative Health Behaviors On Female Mice And/Or Their Offspring, Kristen M. Platt
Theses and Dissertations--Pharmacology and Nutritional Sciences
Obesity is an ever-growing concern in the developed world that carries with it a plethora of health issues. For example, obesity increases an individual’s risk for Type 2 Diabetes and cardiovascular disease. Pregnancy is a vital time for a woman to maintain optimal health, both for her own benefit as well as that of her offspring, and yet almost half of women in the United States who are of age to bear children are overweight or obese. In mice, we found that offspring born to dams fed a high fat diet did not have impaired glucose tolerance, contrary to our …