Molecular, Genetic, and Biochemical Nutrition Commons^™

Influences Of High-Fat Diet And Antrodia Camphorata In Early Life On Intestinal Tumorigensis Later In Life, Ting-Chun Lin

Doctoral Dissertations

Young-onset colorectal cancer (CRC) is a growing public health concern globally due to the increasing prevalence of westernized lifestyles during childhood and adolescence. Meanwhile, there have been reports of health-promoting effects, such as anti-inflammatory and anti-cancer properties, associated with Antrodia camphorata (AC), a unique fungus native to Taiwan. This study aimed to investigate the impact of early-life high-fat diet (HF) and AC supplementation on intestinal tumorigenesis in young adulthood, using APC^1638N mice. Additionally, the study aimed to determine the role of Turicibacter, a probiotic negatively associated with diet-induced obesity, in colorectal tumorigenesis, and to explore the anti-cancer mechanism …

Retinoic Acid, Insulin, And Cycloheximide Alter Glycogen Homeostasis In Differentiating L6 Myoblasts, Aaron Armstrong

Doctoral Dissertations

Glycogen synthesis in skeletal muscle (SM) is responsible for the majority of post-prandial glucose disposal in healthy individuals. In type 2 diabetes mellitus (T2DM), compromised skeletal muscle glycogen synthesis contributes to hyperglycemia. L6 rat SM cells can develop insulin resistance with prolonged insulin stimulation and provide an in vitro model for mechanistic dysfunction in glycogen homeostasis. SM glycogen is synthesized by glycogen synthase (GS) in response to insulin stimulation. Canonically, insulin signaling increases GS activity through inhibition of its Ser641 regulator glycogen synthase kinase-3β (GSK3β) by protein kinase B (AKT). Proximal insulin signaling activates AKT via Ser473 phosphorylation which proceeds …

Bifidobacterial Metabolism Of Fucosylated Human Milk Oligosaccharides Influences Structure And Function Of The Infant Gut Microbiome, Liv R. Dedon

Doctoral Dissertations

Human milk contains human milk oligosaccharides (HMOs) that are indigestible and pass intact through the infant gastrointestinal tract where they are available for microbial metabolism. HMOs incorporate the same monosaccharide building blocks but vary structurally in primary sequence of monomeric components. Primary sequences are further diversified by degree of polymerization, branching, and secondary modifications such as fucosylation. Fucosylated HMOs (fHMOs) are highly abundant and can account for over 30% of total HMOs. Infant-colonizing Bifidobacterium longum subsp. infantis (B. infantis) possesses a specialized gene cluster conveying the ability to metabolize fHMOs. This study presents an in-depth analysis of B. …

Metabolism In The Colonocyte: Where Bacteria And Diet Meet, Bohye Park

Doctoral Dissertations

The host-microbiome interaction and the functions of microbial-derived metabolites, including butyrate, are important in colon health. Butyrate is the preferred energy source in colonocytes and has multiple physiological functions in the colon. A metabolic shift in colonocytes toward increased glucose utilization from butyrate oxidation is followed by several critical genetic modifications in cancerous colonocytes. Moreover, it has been suggested that the gut-microbiota composition is influenced by environmental factors, such as diets and the host's physiological status. Therefore, an understanding of the role of colonocyte metabolism toward impacting the host-microbiota commensal relationship would be an important step in understanding the functional …

The Studies Of Effects Of Vitamin A Status On Type 2 Diabetes In Zucker Diabetic Fatty Rats And Retinoic Acid On Glucose Transporter 4 Expression In L6 Cells, Tiannan Wang

Doctoral Dissertations

The epidemic of metabolic diseases such as diabetes has become a public health concern. Previous research data from our lab have shown that vitamin A (VA) status and retinoic acid (RA), a metabolite of VA, contribute to the glucose and lipid metabolism in the body and cells. As the skeletal muscle contributes to metabolic homeostasis, the effects of VA signaling system on its glucose metabolism are worth to be investigated. Here in this dissertation, the following two projects were carried out to study the VA’s role in the control of metabolism. (1) The effects of VA status on the development …

Effects Of N-3 Pufa-Derived Epoxides Combined With Seh Inhibition On Brown Adipose Tissue And Brown Adipocytes In Obesity, Yang Yang

Doctoral Dissertations

Brown adipose tissue (BAT) has become a promising target for obesity treatment and prevention. However, effective dietary factors to promote BAT mass and function have not been identified. 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) are two prominent epoxy fatty acids (EpFAs) produced from n-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively. EpFAs are quickly metabolized to less active diols by soluble epoxide hydrolase (sEH). In this dissertation, the effects of an sEH inhibitor (t-TUCB) (which stabilizes EpFAs) alone or combined with n-3 EpFAs on thermogenic activity in the BAT and brown adipocytes in …

Novel Insights Into The Role Of Pyruvate Kinase M2 In Podocyte Homeostasis And Function, Mohammed Alquraishi

Doctoral Dissertations

Background: Renal diseases are major health concerns and among the top ten leading causes of death in the US. A large number of these diseases are characterized by deterioration in glomerular structure and function, leading to reduced filtration capacity and proteinuria. Glomerulus podocytes are epithelial cells that maintain glomerular integrity and act as a defense mechanism against proteinuria. Recent advances in renal research suggested a novel role of glycolysis and its related enzymes, pyruvate kinase M2 (PKM2) in particular, in the progression of renal diseases. However, the precise role of PKM2 in podocyte homeostasis and its contribution to glomerular function …

The Prevention Of Obesity-Associated Colorectal Cancer Via Dietary Suppression Of Inflammation-Driven Wnt-Signaling, Jinchao Li

Doctoral Dissertations

Colorectal cancer (CRC) is the third leading cause of cancer deaths in the United States. A number of population studies have established that modifiable lifestyle factors such as obesity plays an important role in colorectal carcinogenesis. In the United States, more than one-third of adults are obese and obesity prevalence rates have no sign of decrease. Therefore, the development of effective strategies to prevent obesity-induced CRC is a public health priority. This study aimed to investigate whether genetic or dietary strategies can prevent obesity-induced CRC and determine the potential molecular mechanisms underlying the prevention effects of these strategies. We used …

Combination Regimens Using Dietary Components For The Chemoprevention Of Colorectal Cancer And Inflammation, Christina Dimarco-Crook

Doctoral Dissertations

ABSTRACT COMBINATION REGIMENS USING DIETARY COMPONENTS FOR THE CHEMOPREVENTION OF COLORECTAL CANCER AND INFLAMMATION September 2018 CHRISTINA DIMARCO-CROOK, B.S., IMMACULATA UNIVERSITY M.S., DREXEL UNIVERSITY Ph.D., UNIVERSITY OF MASSACHUSETTS AMHERST Directed by: Professor Hang Xiao Dietary components have been found to effectively modulate multiple deregulated signaling pathways associated with the initiation and progression of carcinogenesis and inflammation in cellular and animal models. However, clinical studies have shown mixed results when examining the efficacy of individual dietary components, perhaps suggestive of the synergism that exists between multiple components within a particular food and the diet as a whole. Additional research is needed …

Epigenetic Modification Of Vitamin D-Induced Gene Expression In Human Colorectal And Breast Cancer Cell Lines, Sharmin Hossain

Doctoral Dissertations

Epigenetics is the study of the regulation of genes that is not dependent on nucleotide sequence. This may include heritable changes in gene activity and expression but also those that are not heritable. In recent years, epigenetic researchers have made great strides in understanding the molecular mechanisms behind cellular functions in response to diet, exercise, and other lifestyle modifications, like methylation, histone modification etc. It is now known that the epigenome is critical to healthy human development in addition to genetics, and dietary factors can modulate epigenetic alterations in cells. The classic view of cancer etiology is that genetic alterations …

Butyrate, A Major Bacterial-Derived Metabolite: Understanding Of Butyrate Metabolism In Cancerous Colonocytes, Anna Han

Doctoral Dissertations

The prohibitory effects of dietary fiber in colorectal cancer have been identified, although the detailed mechanism of this beneficial effect remain unclear. Butyrate, a fermentation metabolite of fiber, has anti-cancer properties by inhibiting cell proliferation and increasing cell apoptosis in cancer cells. A major mechanism, whereby butyrate exerts anti-cancer effects in colorectal cancer, is its role as an HDAC inhibitor. Moreover, it has been suggested that the metabolic fate of butyrate is significantly related to its role as an HDAC inhibitor. Therefore, understanding butyrate metabolism in cancerous colonocytes sheds important light on how butyrate has its selective and inhibitory effects …

Long-Term Treatment With Insulin And Retinoic Acid Increased Glucose Usage In L6 Muscle Cells Via Glycogenesis, Matthew Ray Goff

Doctoral Dissertations

Skeletal muscle glucose metabolism can affect whole body glucose homeostasis significantly. Vitamin A (VA) plays a role in a number of physiological functions including glucose metabolism. However, its role in skeletal muscle glucose metabolism has not been well established. Insulin controls glucose metabolism in the skeletal muscle via the regulations of glucose uptake, glycogenesis, and glycolysis. We hypothesize that insulin and VA signaling pathways may converge to regulate glucose metabolism in skeletal muscle. Here, the effects of retinoic acid (RA) alone and in combination with insulin on glucose utilization in rat L6 muscle cells were studied. L6 cells were treated …

Chemopreventive Effects Of Polymethoxyflavones, Xian Wu

Doctoral Dissertations

Colon cancer is one of the major global public health issues, which severely threatens human health. Polymethoxyflavones (PMFs), a unique class of flavonoids, are abundantly and almost exclusively found in the peel of sweet oranges (Citrus sinensis) and mandarin oranges (Citrus reticulata). Nobiletin (NBT) is a major citrus flavonoid that has shown various health benefits, including anti-inflammation and anti-carcinogenesis. To better understand the chemopreventive effects of NBT, we systematically investigated the inhibitory effects of dietary NBT on colitis-associated colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice. We found that oral administration of NBT effectively decreased …

Brown And Beige Adipocytes: Effects Of Inflammation And Nutritional Intervention, Jiyoung Bae

Doctoral Dissertations

Recent findings of brown adipocytes and brown-like or beige adipocytes, capable of dissipating energy as heat, in adult humans have promised new hope for obesity treatment and prevention. Understanding of the regulation of brown and beige adipocytes will provide novel strategies to reach the goal. Pattern recognition receptors (PRR) are responsible for inflammation in adipose tissue, which leads to adipose dysfunction and obesity associated chronic diseases. It has been shown that PRR activation induces inflammation, leading to insulin resistance in white adipocytes and white adipose tissue (WAT). However, the roles of PRR activation in brown adipocytes and brown adipose tissue …

Exploring Novel Environmental Link To Obesity: Role Of Parabens In Adipogenesis In Vitro And In Vivo, Pan Hu

Doctoral Dissertations

Parabens are a group of alkyl esters of p-hydroxybenzoic acid that include methylparaben, ethylparaben, propylparaben, butylparaben, and benzylparaben. Paraben esters and their salts are widely used as preservatives in cosmetics, toiletries, food, and pharmaceuticals. Humans are exposed to parabens through the use of such products from dermal contact, ingestion, and inhalation. The extent of the exposure is reflected by the frequent detection of these compounds in urine samples in the general population. Moreover, parabens have been detected in human serum, milk, placental tissues and breast tumor tissues. Parabens have been shown to preserve estrogenic/antiandrogenic effects, and can activate peroxisome proliferator-activated …

Calcium And Leucine Modulation Of Airway Inflammation, Patricia Louise Brown

Doctoral Dissertations

Over the past several decades the prevalence of obesity and asthma have increased in a parallel fashion. Recent studies reported a positive relationship between the two disorders that may in fact be causal. Although the link between obesity and asthma has become widely recognized, the underlying pathophysiological connection is not elucidated. Increased markers of inflammatory and oxidative stress are present in obesity and asthma suggesting the link is immunological. The systemic inflammation observed in obesity may potentially initiate adverse affects in the airways. Previous studies have shown that consumption of dairy foods (rich in calcium and leucine) suppress 1,25-dihydroxycholecalciferol (calcitriol) …

Role Of Vitamin A Status And Its Catabolism In The Regulation Of Glucose And Lipid Homeostasis In Rats Under Physiological And Disease Conditions, Yang Li

Doctoral Dissertations

The increased number of individuals with metabolic diseases has become a public health concern. Vitamin A (VA, retinol) is required to maintain the general health of an individual. How VA contributes to the regulation of glucose and lipid homeostasis in normal and metabolic disease states is unclear. VA’s physiological activities are mainly mediated by its metabolite, retinoic acid (RA), which activates several transcriptional factors in the nuclear receptor super family and in turn, regulates the expression of numerous genes for macronutrient metabolism. For the RA production, retinol is first oxidized into retinal and then from retinal to RA. We hypothesize …

Cancer Chemoprevention By Dietary Compounds Targeting Angiogenesis, Wasamon Nutakul

Doctoral Dissertations

Cancer remains a leading cause of death worldwide. Due to angiogenesis and metastatic potency of cancer, chemotherapies are not adequate for metastatic tumor. We investigated anti-carcinogenic effects of resveratrol in comparison to those of pterostilbene in colon cancer cells. We found superior activities of pterostilbene over resveratrol in growth inhibition as well as apoptosis induction. Higher Intracellular concentration of pterostilbene could contribute to its higher potency in anti-carcinogenesis; however, both resveratrol and pterostilbene failed to inhibit colon cancer cell migration in vitro. Polymethoxylatedflavones (PMFs) found exclusively in citrus fruits have shown inhibitory effects against cancer. We investigated their anti-angiogenic …

Role Of Leucine In Modulation Of Mitochondrial Biogenesis And Sirt1-Ampk Signaling In C2c12 Myotubes, Chunzi Liang

Doctoral Dissertations

Mitochondrial dysfunction in skeletal muscle has been considered as a crucial step in the development of metabolic diseases, including insulin resistance syndrome, type 2 diabetes and cardiovascular diseases. Previous studies have demonstrated that dietary branched-chain amino acids, particularly leucine, protects against high-fat diet induced impairment of mitochondria and insulin resistance in skeletal muscle and adipose tissue through mTOR-dependent and independent pathways. In addition, previous ex vivo and in vitro approaches from this laboratory indicate that leucine and its metabolites (HMB and KIC) stimulate mitochondrial biogenesis and promote energy partitioning from adipocytes to muscle cells, partially through SIRT1 signaling. Moreover, recent …

Feeding State, Vitamin A Status And Atypical Protein Kinase C Modulate The Insulin-Regulated Gene Expression In Rat Hepatocytes, Wei Chen

Doctoral Dissertations

Hormonal and nutritional stimuli coordinately regulate the glucose and lipid metabolism in the liver. Dysregulated hormonal balance and nutrient metabolism not only disrupt the energy homeostasis, but also predispose individuals to the development of obesity and its related metabolic diseases. Research presented in this dissertation investigated the effects of a nutritional factor, vitamin A (VA), and a potential component of insulin signaling cascade, atypical protein kinase C (aPKC), on the glucose and lipid metabolic genes transcription in primary hepatocytes from Zucker lean (ZL) and fatty (ZF) rats.

To examine VA effects, we put ZL and ZF rats with different VA …

The Effects Of Leucine And Dairy Products On Adipose Tissue Inflammation: The Role Of Adipocyte Derived Microvesicles, Benjamin Jones Curry

Doctoral Dissertations

Obesity is characterized by chronic oxidative and inflammatory stress, and adipose tissue is a significant source of inflammatory cytokines. Previous studies demonstrated that dairy products (rich in calcium and leucine) can alleviate obesity-associated inflammatory stress through suppression of 1, 25-dihydroxycholecalciferol (calcitriol) with calcium and the high leucine content in dairy. We have also shown leucine treatment increases anti-inflammatory adiponectin expression and decreases pro-inflammatory cytokines TNF-a [alpha], MCP-1, and IL-6 expression in adipocytes. Therefore, we sought to determine if these alterations in inflammatory cytokine production could have a functional effect on the inflammatory process, specifically monocyte – endothelial cell adhesion as …

Role Of Retinoids In The Regulation Of Hepatic Glucose And Lipid Metabolism, Rui Li

Doctoral Dissertations

The liver plays an important role in controlling glucose and lipid homeostasis. Metabolic abnormalities such as obesity and type 2 diabetes are often associated with profound changes in the expression of genes involved in hepatic glucose and lipid metabolism. Dietary nutrients provide us with macronutrients for energy and micronutrients for maintenance of general health. However, the effects of individual micronutrients on the development of metabolic diseases are unknown. Sterol regulatory element binding protein-1c (SREBP-1c) is the master regulator of fatty acid synthesis, and glucokinase (GK) is the key enzyme in glucose metabolism. Based on the preliminary results from our laboratory …

Effects Of Folate Availability On Expression Of Adipocyte Metabolic Genes Via Modulation Of Dna Methylation, Julia Stair Gouffon

Doctoral Dissertations

Epigenetic modifications serve as a means of intermediate gene expression control and nutritional inputs may modify methylation patterns in regulatory regions of genes. Therefore, we proposed that specific nutrient availability of folate affects adipocyte development and metabolism through impacting the one-carbon cycle and subsequent DNA methylation patterns. Accordingly, we sought to determine if the methylation level of CpG islands could be influenced in adipocytes and if so, how this might affect gene signaling in mature adipocytes. We treated adipocytes with 0 to 0.9 millimolar [mM] folate, the methyl donor S-adenosylmethionine (SAMe) and the methylation inhibitor, 5-aza-2-deoxycitidine (2-DC) both during adipocyte …

Genetic And Nutritional Studies To Elucidate The Role Of Adipose Tissue In The Pathogenesis Of Metabolic Syndrome, Nishan Sudheera Kalupahana

Doctoral Dissertations

Obesity is a major health problem in the United States and worldwide. It increases the risk for type-2 diabetes and cardiovascular diseases. A chronic low-grade inflammation occurring in white adipose tissue (WAT) is causally linked to the development of insulin resistance (IR), metabolic syndrome and obesity-associated chronic diseases. The aim of this dissertation research was to elucidate the WAT function in metabolic syndrome using genetic (overexpression of an adipose pro-inflammatory hormone, angiotensinogen) and nutritional manipulations/approaches (caloric restriction and omega-3 fatty acids), with specific emphasis on the role of inflammation.

Previous research indicates that WAT renin-angiotensin system (RAS) is overactivated in …

Mechanisms Associated With The Chemotherapeutic Effects Of Zyflamend, A Multi-Herbal Extract, On Advanced Prostate Cancer, E-Chu Huang

Doctoral Dissertations

Advanced prostate cancer (PrC) is the second leading cause of death from cancer in US males. Advanced PrC cells are initially androgen-sensitive and thus androgen ablation therapy causes tumors to undergo regression and fall into a remission phase where residual cells remain dormant while androgen levels remain very low. Unfortunately, this phase usually lasts 3 to 5 years prior to tumor relapse, where the tumor cells re-grow in the absence of androgens. This form of the disease is aggressive and invariably fatal. In this study, we investigated the effects of a combination of herbal extracts on various stages of PrC, …