- Folate and B Vitamins Research
- Epigenetics and DNA Methylation
- Sulfur Compounds in Biology
- Birth, Development, and Health
- Amino Acid Enzymes and Metabolism
- Nutritional Studies and Diet
- Food composition and properties
- Genetics, Aging, and Longevity in Model Organisms
- Glutathione Transferases and Polymorphisms
- Gut microbiota and health
- RNA modifications and cancer
- Adipose Tissue and Metabolism
- Diet and metabolism studies
- Endoplasmic Reticulum Stress and Disease
- Cancer, Hypoxia, and Metabolism
- Fibroblast Growth Factor Research
- Cancer-related gene regulation
- Cancer Research and Treatments
- Pregnancy and Medication Impact
- Sphingolipid Metabolism and Signaling
- Autophagy in Disease and Therapy
- Dietary Effects on Health
- Free Radicals and Antioxidants
- Aldose Reductase and Taurine
- Adenosine and Purinergic Signaling
Orentreich Foundation for the Advancement of Science
2015-2025
South Dakota State University
2013-2016
Pennsylvania State University
2008-2014
Penn State Milton S. Hershey Medical Center
2011
Hershey (United States)
2011
Society of Environmental Toxicology and Chemistry
2009
University of Idaho
2004-2006
Abstract Dietary modulation of the gut microbiota impacts human health. Here we investigated hitherto unknown effects resistant starch type 4 (RS4) enriched diet on composition and short-chain fatty acid (SCFA) concentrations in parallel with host immunometabolic functions twenty individuals signs metabolic syndrome (MetS). Cholesterols, fasting glucose, glycosylated haemoglobin proinflammatory markers blood as well waist circumference % body fat were lower post intervention RS4 group...
Nutrition and metabolism are known to influence chromatin biology epigenetics through post-translational modifications, yet how this interaction influences genomic architecture connects gene expression is unknown. Here we consider, as a model, the metabolically-driven dynamics of H3K4me3, histone methylation mark that encode information about active transcription, cell identity, tumor suppression. We analyze genome-wide changes in H3K4me3 response alterations methionine availability both...
A metabolic health crisis is evident as cardiovascular diseases (CVD) remain the leading cause of mortality in United States. Effects resistant starch type 4 (RS4), a prebiotic fiber, comprehensive management syndrome (MetS) unknown. This study examined effects blinded exchange RS4-enriched flour (30% v/v) with regular/control (CF) diet on multiple MetS comorbidities. In double blind (participants–investigators), placebo-controlled, cluster cross-over intervention (n = 86, age≥18, 2–12 week...
Lifelong dietary methionine restriction (MR) is associated with increased longevity and decreased incidence of age-related disorders diseases in rats mice. A reduction the levels oxidative stress may be a contributing mechanistic factor for beneficial effects MR. To examine this, we determined an 80% Met on different biomarkers antioxidant pathways blood, liver, kidney brain rat. Male F-344 were fed control (0.86% methionine) or MR (0.17% diets up to six months. Blood tissues analyzed...
Dietary restriction of methionine (Met) and cysteine (Cys) delays the aging process aging-related diseases, improves glucose fat metabolism reduces oxidative stress in numerous laboratory animal models. Little is known regarding effects sulfur amino acid humans. Thus, our objectives were to determine impact feeding diets restricted Met alone (MetR) or both Cys (total acids, SAAR) healthy adults on relevant biomarkers cardiometabolic disease risk. A controlled study. We included 20 (11...
Identifying novel approaches to combat obesity is important improve health span. It was hypothesized that methionine restriction (MR) will induce weight loss in obese mice by reducing adipose tissue mass caused increased energy expenditure and reprogramming of homeostasis. The roles adiponectin (ADIPOQ) fibroblast growth factor 21 (FGF21) during MR were also tested.
Sulfur amino acid restriction (SAAR), lowering the dietary concentration of sulfur acids methionine and cysteine, induces strong anti-obesity effects in rodents. Due to difficulties formulating SAAR diet for human consumption, its translation is challenging. Since our previous studies suggest a mechanistic role low glutathione (GSH) SAAR-induced effects, we investigated if pharmacological GSH recapitulates lean phenotype mice on acid-replete diet. Male obese C57BL6/NTac were fed high-fat...
Abstract The mechanisms underlying life span extension by sulfur amino acid restriction (SAAR) are unclear. Cysteine and methionine essential for the biosynthesis of proteins glutathione (GSH), a major redox buffer in endoplasmic reticulum (ER). We hypothesized that SAAR alters protein synthesis modulating milieu. Male F344‐rats were fed control (CD: 0.86% without cysteine) diets (0.17% 12 weeks. Growth rates, food intake, cysteine GSH levels, associated with status translation, fractional...
Decreasing the dietary intake of methionine exerts robust anti-adiposity effects in rodents but modest humans. Since cysteine can be synthesized from methionine, animal diets are formulated by decreasing and eliminating cysteine. Such exert both restriction (MR) (CR), that is, sulfur amino acid (SAAR). Contrarily, SAAR for human consumption included cysteine, thus might have exerted only MR. Epidemiological studies positively correlate body adiposity with plasma not suggesting CR, MR, is...
Abstract Protein folding in the endoplasmic reticulum (ER) requires a high ratio of oxidized to reduced glutathione (GSSG/rGSH). Since GSSG/rGSH depends on total (tGSH = GSSG + rGSH) levels, we hypothesized that limiting GSH biosynthesis will ameliorate protein misfolding by enhancing ER oxidative milieu. As proof-of-concept, used DL-buthionine-(S,R)-sulfoximine (BSO) inhibit Akita mice, which are prone proinsulin misfolding. We conducted 2-week intervention investigate if BSO was safe and...
A guanine-adenine-guanine (GAG) repeat polymorphism with 5 different alleles (4, 7, 8, 9, and 10 repeats) in the 5' untranslated region (UTR) of GCLC has been associated altered GCL activity glutathione (GSH) levels. We investigated whether this affects either transcription or translation using luciferase reporter constructs containing variant UTRs. Higher was observed HepG2 human embryonic kidney 293 (HEK293) cells transfected 8 9 repeats than 4, (P<0.05). In cell-free lysates, GAG number...
Glutathione (GSH), the major intracellular antioxidant, protects against cancer development by detoxifying carcinogens and free radicals strengthening immune system. Recently, a GAG-trinucleotide repeat polymorphism in 5'-untranslated region of gene for rate-limiting enzyme GSH biosynthesis, γ-glutamine cysteine ligase (GCL), was shown to be associated with lowered GCL activity levels vitro vivo. We tested hypothesis that this functional is risk lung aerodigestive tract cancers. To end, we...
Abstract Trade‐offs in life‐history traits are clinically and mechanistically important. Sulfur amino acid restriction (SAAR) extends lifespan. But whether this benefit comes at the cost of other including stress resistance growth is unclear. We investigated effects SAAR on markers (body weight, IGF1, IGFBP3) physiological stresses. Male‐F344 rats were fed control (0.86% Met) (0.17% diets starting 2, 10, 20 months. Rats injected with keyhole‐limpet‐hemocyanin (KLH) to measure immune...
Abstract Diet can affect health and longevity by altering the gut microbiome profile. Sulfur amino acid restriction (SAAR), like caloric restriction, extends lifespan. But, its effect on profile functional significance of such effects are understudied. We investigated whether SAAR alters bile composition, an index microbial metabolism. also compared these changes with those induced a 12% low-calorie diet (LCD). Male 21-week-old C57BL6/J mice were fed control (CD; 0.86% methionine), (0.12%...
This study was designed to investigate possible additive or synergistic action among sphingo-myelin (SPH) cis-9 trans-11-conjugated linoleic acid (CLA), and butyrate (BTY) against colon cancer modulation of immune functions in vivo male Sprague-Dawley rats. Each the 5 groups rats fed either 35 mg SPH, 100 CLA, BTY/kg body weight, a com-bination 3 compounds at same doses, none compounds, for 7 wk. Rats were injected with azoxymethane, carcinogen, induce formation aberrant crypt foci,...
Abstract Nutrition exerts profound effects on health and dietary interventions are commonly used to treat diseases of metabolic etiology. Although cancer has a substantial component, the principles that define whether nutrition may be influence tumour outcome unclear. Nevertheless, it is established targeting pathways with pharmacological agents or radiation can sometimes lead controlled therapeutic outcomes. In contrast, specific could targeted in standard therapies not known. We now show...
Summary Decreasing dietary intake of methionine exerts robust anti-adiposity effects in rodents but modest humans. Since cysteine can be synthesized from methionine, animal diets are formulated by decreasing and eliminating cysteine. Such exert both restriction (MR) (CR), i.e., sulfur amino acid (SAAR). Contrarily, human used clinical studies did not eliminate thus might have exerted only MR. Epidemiological positively correlate body adiposity with plasma suggesting that CR, MR, is...