The 2022-2023 LAUNCHED Pilot & Feasibility Awardees
- Aline Zaparte
- Bruna Visniauskas
- Maria Sanchez-Pino
A novel link between nocturnal blood pressure and circadian clocks in adipose tissue during menopause
Inadequate sleep disrupts the precise orchestration of circadian clocks, dysregulates glucose metabolism in adipose tissue, and increases the risk for obesity, hypertension, and cardiovascular diseases. Sleep disruption is one of the most common symptoms during the menopausal transition and post menopause, but whether it exacerbates the detrimental impact of menopause on cardiovascular and metabolic function is not known. To fill this knowledge gap, we propose to study the impact of sleep restriction on the cardiometabolic phenotype using a mouse model that mimics menopause. Specific Aim 1: elucidate the direct consequences of estrogen loss and sleep restriction on blood pressure rhythms, and cardiometabolic responses in females fed a high fat diet, and Specific Aim 2: will assess the impact of sleep restriction on blood pressure rhythms and characterize changes in the metabolic profile in a cohort of obese postmenopausal women.
The Effect of Weight Loss by Pharmacotherapy on Chronic Pro-tumor Inflammatory Cells
Obesity is a progressive disease of excess adiposity that increases the risk of developing many types of cancer. Louisiana has the fifth-highest all-cancer mortality rate in the nation and has the highest rate of severe obesity in the US. Observational studies report that bariatric surgery, an anti-obesity intervention, is associated with a decreased cancer incidence. However, only 1-2% of people get access to bariatric surgery. Therefore, it is essential to understand the anti-neoplastic mechanism underlying bariatric surgery to determine if more accessible treatments, such as medication, could also provide the same clinical benefit operating under the same mechanism. Bariatric surgery reduces body weight, facilitates improvement in metabolic changes, and attenuates inflammation. Evidence indicates that an increased number of myeloid-derived immunosuppressive cells (MDSC) are critical for the long-lasting inflammatory condition that facilitates malignancy. We have found that bariatric surgery significantly reduces the number of circulating low-density neutrophils (LDNs), a subset of inflammatory granulocytic cells that may act as precursors of MDSC. This finding suggests that bariatric surgery could interrupt obesity-induced malignancy by diminishing LDN/MDSC. Whether different modalities of weight management impede LDN/MDSC accumulation, and therefore, mitigate the malignancy risk in obesity, could foster a new treatment paradigm in cancer prevention. Consequently, the overall objective of this application is to determine the ability of weight management with glucagon-like peptide-1 receptor agonists and phentermine/topiramate medications to influence the numbers and functional phenotype of LDN/MDSC in blood. We hypothesize that patients undergoing pharmacological treatment as part of their standard-of-care for obesity, achieving clinically significant weight loss at 6 months (defined as > 5% of total body weight), and metabolic improvement have reduced the number of and altered the inflammatory phenotype of LDN/MDSC in blood. Two specific aims are proposed to test our hypothesis: Specific Aim 1: To determine changes in circulating LDN/MDSC numbers, BMI, and inflammatory and metabolic markers after weight loss medication compared to baseline; and Specific Aim 2: To determine the contribution of medication on LDN/MDSC phenotype.
Broccoli extract supplementation and gastrointestinal health in older adults with active alcohol use and low diet quality
Aging confers an increased susceptibility to multimorbidity, in part due to dysregulated immunity and oxidative stress. Alcohol use disorder (AUD) in older adults is increasingly prevalent, as is poor nutritional status. Drinking is the 3rd most prevalent health behavior associated with adverse health outcomes in the United States and emerging data suggest an interaction with diet. Our group has reported that higher lifetime alcohol consumption is associated with geriatric frailty syndrome. Further, in both preclinical models and in humans, we have reported that alcohol impairs the gastrointestinal barrier and promotes mucosal inflammation, which contributes to distal end-organ disfunction, in part mediated by intestinal dysbiosis. In preliminary studies to support this pilot project in humans, we tested generally recognized as safe (GRAS) compounds in rodent model of alcohol use as a strategy to mitigate detrimental effects of gut leak and inflammation. Broccoli is considered a health-promoting food, and its efficacy has been tested with diseases closely related with geriatric comorbidities, such as neurodegenerative diseases, cancer, and osteoporosis. Our preclinical experiments using broccoli sprouts extract (BSE) showed significant reductions in alcohol-induced gut barrier leak, inflammation, and oxidative stress. My hypothesis is that BSE will reduce gut leak and systemic biomarkers of inflammation and oxidative stress. My hypothesis will be tested in a pilot clinical trial testing in effect of 4 weeks BSE diet supplementation in older adults that consume alcohol and a nutritionally poor diet. Specific Aim 1: To test the effect of BSE on gut leak using PEG400 translocation. Specific Aim 2: To test the effect of BSE on peripheral blood pro-inflammatory mediators and immune cells. Specific Aim 3: To test the effect of BSE on oxidative stress and antioxidant capacity in peripheral blood.
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