Molecular, Genetic, and Biochemical Nutrition Commons^™

The Role Of Hypoxia Inducible Factor-1 Alpha (Hif-1⍺) In Human Coronavirus Oc43 Infection, Olivia Faith Riffey

Masters Theses

The importance of altering host cell metabolism for promoting infection and propagation of coronaviruses highlights the intricate play between viruses and the cells they infect (1). Upregulation of the glycolytic pathway in host cells infected with coronaviruses was observed in single-cell RNAseq, although the mechanism(s) that mediate this effect are still being investigated(2). Hypoxia-inducible factor-1 alpha (HIF-1⍺) is a transcription factor that regulates many glycolytic enzymes. Recent studies have identified SARS-CoV-2 upregulation of HIF-1⍺, which suggests it may have an important role in virus production (3, 4). However, the exact role and physiological relevance of HIF-1⍺ during viral infection is …

Switching Palmitoyl And Oleoyl Positions In Sn-2 And Sn-3 Of A Triacylglycerol Led To Differential Body Weight Gain Rates And Hepatic Gene Expressions In Mice Fed A High-Fat Diet, Xinge Hu

Masters Theses

Alterations of triacylglycerol (TAG) are associated with metabolic diseases such as obesity and diabetes. The fatty acyl groups in a TAG molecule determine its characteristics from melting temperature to digestion and absorption. We hypothesize that the TAG fatty acyl position affects the body weight (BW) gain and lipid metabolism in mice fed a high-fat diet (HFD, 36 % w/w diet). Six-week-old male C57BL/6J mice were randomly assigned to 3 dietary groups, 1,2-dipalmitoyl-3-oleoylglycerol (PPO), 1,3-dipalmitoyl-2-oleoylglycerol (POP), and chow control. The food intake and BW were measured daily during 6 weeks of treatment. The PPO group had significantly higher food intake, caloric …

Roles Of Select Cytochrome P450 Epoxygenases In Brown Adipogenesis, Katherine Marie Graham

Masters Theses

Brown adipose tissue (BAT) has recently emerged as a novel target for obesity treatment and prevention. Cytochrome P450 (CYP) epoxygenases, primarily CYP2J and CYP2C isoforms, produce epoxy fatty acids (EpFAs), which have been suggested to play important roles in the regulation of white adipogenesis and obesity. However, adipocyte-specific expression of CYP epoxygenases has not been extensively analyzed, and the roles of CYP epoxygenases in brown adipogenesis remain unexplored. In this study, we examined mRNA levels of Cyp2j and Cyp2c isoforms during murine and human brown and white adipocyte differentiation and in various adipose tissue depots of high-fat diet (HFD)-fed and …

Beneficial Effects Of Naringenin And Indomethacin On White And Brown Adipocytes, Jamie Ann Kearns

Masters Theses

As obesity continues to grow and medical costs in the United States are estimated at $147 billion annually, novel ways to prevent and treat obesity are needed. One approach is to promote thermogenesis to improve energy balance by increasing the activities of thermogenic brown and beige adipocytes.

Naringenin, a citrus flavanone, has been shown to act as anti-inflammatory and lipid lowering agent as well as activate PPARgamma. However, it is unclear whether it can activate thermogenic activity in white adipocytes, i.e., promote formation of beige adipocytes. Indomethacin (INDO) is an FDA approved drug used to treat pain related to inflammation …

The Suppressive Effects Of 1,25-Dihydroxyvitamin D3 And Vitamin D Receptor On Brown Adipocyte Differentiation And Mitochondrial Respiration, Carolyn Jeanne Ricciardi

Masters Theses

The vitamin D system plays a role in metabolism regulation. It has been reported that 1,25(OH)₂D₃ [1,25-dihydroxyvitamin D] suppresses 3T3-L1 adipocyte differentiation. Vitamin D receptor (VDR) knockout mice showed increased energy expenditure whereas mice with adipose-specific VDR over expression showed decreased energy expenditure. Brown adipose tissue (BAT), which functions in non-shivering thermogenesis by uncoupling ATP synthesis from oxidation, plays important roles in energy expenditure. However, the effects of 1,25(OH)₂D₃ on brown adipocyte differentiation and mitochondrial respiration have not been studied. Reported here is the mRNA expression of VDR, UCP1, and CYP27B1 (1α[alpha]- hydroxylase) in …

Regulation Of Apolipoprotein C-Iii Gene Expression By Nuclear Receptors Hepatocyte Nuclear Factor 4 Alpha And Chicken Ovalbumin Upstream Promoter Transcription Factor Ii, But Not Retinoids In Hepatic Cells, Meredith Lee Howell

Masters Theses

Retinoic acid (RA) treatment induces hyperlipidemia in humans and animals. RA regulates the expression levels of various genes through the induction, repression, or coactivation of nuclear receptors, mediating its effects. RA-induced hyperlipidemia has been attributed to the induction of apolipoprotein CIII (gene, Apoc3), which inhibits lipoprotein lipase activity (LPL). We have shown that vitamin A (VA) status and retinoid treatment regulates hepatic lipogenic gene expression, suggesting that the induction of lipogenic genes may also contribute to hyperlipidemia. To test the hypothesis that retinoids may not affect Apoc3 expression, we analyzed the expression levels of Apoc3 mRNA in response to …

Activation Of Nucleotide Binding Oligomerization Domain Containing Protein 1 In 3t3-L1 Adipocytes: Effects On Adipocyte Differentiation And Lipolysis, Jaanki Shamb Purohit

Masters Theses

Obesity, defined as having excess adipose tissue, is associated with chronic inflammation. Adipose tissue is made up of many cell types, including preadipocytes and adipocytes. Both preadipocytes and adipocytes express pattern recognition receptors that play important roles in innate immunity. Two families of pattern recognition receptors that have been studied in adipose tissue are Toll-like receptors (TLRs) and NOD-like receptors (NLRs). Activation of TLR2 and TLR4 has been shown to lead to proinflammatory response in adipocytes, which is shown to suppress adipocyte differentiation and stimulate lipolysis, one of the major physiological functions of adipocytes. However, the effects of NOD activation …

Role Of Beta-Hydroxy-Beta-Methylbutyrate (Hmb) In Leucine Stimulation Of Mitochondrial Biogenesis And Fatty Acid Oxidation, Renee Ashley Stancliffe

Masters Theses

Mitochondrial dysfunction and the resulting oxidative stress is widely recognized as a contributing factor to the development of numerous pathophysiologies including obesity, diabetes, cardiovascular disease, sarcopenia, liver disease, dementia, amongst others. Mitochondrial dysfunction results in a reduced mitochondrial number and oxidative capacity, causing an increase in free radical production and consequently oxidative stress. As such, the characterization of compounds that can upregulate mitochondrial biogenesis and function could provide the foundation for the development of therapeutic nutraceuticals that promote mitochondrial health, and consequently reduce oxidative stress. Leucine is well recognized to stimulate muscle protein synthesis, and we have recently demonstrated that …

The Effects Of Leucine On Mitochondrial Biogenesis And Cell Cycle In A-375 Melanoma Cells, Tia Marie Filhiol

Masters Theses

Most cancer cells undergo the Warburg effect, a shift from oxidative to glycolytic metabolism accompanied by suppression of p53. We have demonstrated leucine stimulation of mitochondrial biogenesis, fatty acid oxidation, and p53 expression in both muscle and fat cells. Accordingly, we now sought to determine if leucine stimulates mitochondrial biogenesis and exit from cell cycle in A-375 melanoma cells. Because these cells use glucose as their primary substrate, cells were grown under both standard (11.1 mM) and reduced (5.5 mM) glucose conditions. Increasing glucose reduced mitochondrial mass 50-60%, and accelerated cell proliferation by ~20%. Leucine (0.25, 0.5, 0.75, and 1.0 …

Angiotensinogen Gene Silencing Reduces Lipid Accumulation And Inflammation In Cultured 3t3-L1 Adipocytes, Wenting Xin Carroll

Masters Theses

Obesity is characterized by metabolic complications which are related to several life-threatening diseases. Dysregulated inflammatory adipokines secretion from adipose tissue is believed as the major contributor to obesity-associated local and systemic inflammation, insulin resistance, and other metabolic dysfunctions.

Numerous studies in our lab and others pointed to the role of local adipose tissue renin-angiotensin system (RAS) in the pathogenesis of obesity, inflammation and insulin resistance. We hypothesized that adipocytes-derived angiotensinogen (Agt) played a critical role in adipogenesis and/or lipogenesis as well as adipose inflammation. To test, we established 3T3-L1 preadipocytes stably transfected with Agt-shRNA or scrambled sequence (Sc-shRNA). Transfected preadipocytes …

Angiotensin Iv And The Molecular Mechanisms Involved In The Development Of Insulin Resistance In 3t3-L1 Adipocytes, Julie Anne Jungwirth

Masters Theses

This study explored angiotensin IV’s (Ang IV) affects on the signaling pathways involved in the development of insulin resistance in 3T3-L1 adipocytes. Ang IV, working through the AT₄ receptor, interferes with insulin signaling through the blockade of the phosphatidylinositol 3-kinases (PI3K)/Akt pathway and through activating mitogen activated protein kinases (MAPK): extracellular signal regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK) which are known to impair insulin receptor substrate-1 (IRS-1) signaling. The expression of AT₄ receptors was confirmed by reverse transcription polymerase chain reaction. Ang IV’s effects were found by treating adipocytes with combinations of Ang IV, AT …

Allometric Scaling Of Dietary Linoleic Acid On Changes In Tissue Arachidonic Acid Using Human Equivalent Diets In Mice, Kylie A Weldon

Masters Theses

The ability to extrapolate nutritional intervention data from experimental rodent models to humans requires standardization of dietary design. The inability to translate the level of nutrients from animal models to humans has contributed to contradictory findings between species. It is hypothesized that dietary linoleic acid (LA) promotes chronic and acute diseases by enriching tissues with arachidonic acid (AA), its downstream metabolite. However, levels of LA in rodent diets are notoriously erratic making interspecies comparisons unreliable. Therefore, the ability to extrapolate the biological effects of dietary LA from experimental rodents to humans necessitates an allometric scaling model that is rooted within …

Regulation Of Angiotensinogen In Adipocytes By Polyunsaturated Fatty Acids, Sarah Jean Fletcher

Masters Theses

Adipose tissue is well-recognized as an endocrine organ which secretes a variety of bioactive molecules, including angiotensin II and its precursor angiotensinogen (Agt). There is mounting evidence linking the adipose renin-angiotensin system (RAS) and diet to obesity and obesity-related disorders. However, research addressing dietary regulation and function of adipose RAS is limited, and the specific mechanisms by which PUFAs modulate the endocrine function of adipose tissue remain largely unclear. There are several potential mechanisms that may mediate PUFA effects on Agt, including toll-like receptor signalling, prostaglandins or PPAR-gamma. Thus, we propose to investigate whether PUFAs differentially modulate Agt expression and …