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Since the beginning of the present century, many workers have been interested in various aspects of insect nutrition. The early investigators were interested in the effects of bacterial action and consequently were led to investigate the effect of sterilization of both the experimental animals and the dietary substrate. Pasteur, although he never attempted to do so himself, once declared to the Academy of Science that he hoped to see a research worker attempt to rear an animal under strictly aseptic conditions. Much of the nutritional literature is concerned with a continuation of this argument. Even today, such eminent workers as Wigglesworth (93), Mansour (63) (64), and Koch (57) (580 (59) are unwilling to define the role played by bacteria in nutrition. Bacteria, regardless of their role, fall into two main categories: those contained in the food; and those living in the mycetomes, which in some cases communicate with the gut. The subject is important because of the fact that bacteria may be capable of fixing free nitrogen or of converting one type of amino acid to another. For very precise work, undoubtedly bacterial action is an important factor. However, in some cases, it is possible to neglect the question of the action of bacteria on the food. In the natural state, the food is certainly contaminated with bacteria, and under normal conditions, there is no such things as asepsis. [...]

<p> Limited data is available to determine the ability of subjective nutrition assessment tools to reliably discover sarcopenia among patients admitted to general medical floors (GMF). Patients were included if subjective global assessment (SGA, nutrition status), abdominal computed tomography (CT, muscle mass in Skeletal Muscle Index (SMI)) scan, and handgrip strength (HGS, muscle function) were completed within 7 days of hospitalization. Sarcopenia was determined using European Working Group on Sarcopenia guidelines (SMI &lt;41 cm²/m² for women, SMI &lt;43 cm²/m² for men with BMI &lt;25 kg/m² or &lt;53 cm2/m² for men with BMI >25 kg/m² and handgrip strength measures &lt;30 kg for men and &lt;20 kg for women). A Pearson's Chi-Squared was utilized to determine associations between sarcopenia and nutrition status. A total of 141 subjects were included, 30% of which were sarcopenic, although only 55% of these patients were correctly classified by SGA. Future research is needed to develop an appropriate nutrition assessment tool to enhance SGA. </p>

<p>The purpose of this study was to identify the prevalence and predictors of the use of high-risk supplements, including those in the herbal, caffeinated, weight-loss, pre-workout, and muscle-building categories, among collegiate athletes. Anonymous surveys, with complete data regarding supplement use, were collected from 557 athletes participating on competitive teams at two NCAA Division 1 schools. A total of 8.3% of participants met criteria for high risk supplement use. Survey results indicated that 20 (3.6%) athletes used herbal, 1 (0.2%) athlete used caffeinated, 5 (0.9%) athletes used weight loss, 28 (5.0%) athletes used pre-workout, and 1 (0.2%) athlete used muscle-building supplements. Significant predictors of supplement use included motivations regarding endurance, fat loss, and increased muscle mass, and status as a 4th year (or later) college student. The reported motivation to use supplements to lose body fat and gain muscle mass emerged as the strongest single predictor of high-risk supplement use.

Epidemiological surveys have shown that premenopausal women are less susceptible to atherosclerosis than men. There is also a positive correlation between the levels of serum triglyceride and the incidence of atherosclerosis. In this study the rat has been used as an experimental model to examine the effects of the prolonged ingestion of 5% sucrose and 5% glucose solutions, in addition to the normal diet. In general, both male and female animals on the sucrose diet showed the greatest increases in body weight and also in the weights of liver, small intestine, heart, kidney and adipose tissue. Male rats had significantly higher levels of serum triglycerides than females and the sucrose diet increased the levels of serum triglyceride to a greater extent than the glucose diet in both sexes. No significant differences in serum phospholipid were observed but, in most cases, serum cholesterol levels were higher in females than in males. The levels of all three lipids in the heart and liver were generally higher in females than in males, but the effect of various diets on these factors were minimal. A study on the effect of the diets on various carbohydrate metabolites demonstrated that hepatic a-glycerophosphate, dihydroxyacetone phosphate and fructose 1,6-diphosphate levels were lower in females than in males. There was, however, no significant sex difference in the level of hepatic fructose 1-phosphate. No dramatic sex differences in these metabolites, were found in heart and kidney. Following the short terra gastric intubation of 70% fructose no sex differences in fructose 1-phosphate levels were observed either in the liver or in the small intestine. Isolated hepatocytes, which responded to physiological levels of glucagon with regard to lipogenesis from glucose and to gluconeogenesis from lactate, were prepared. No sex differences in the capacity of hepatocytes to synthesize either total lipid or triglyceride, from fructose, glycerol or glucose, were observed. However, the incubation of hepatocytes with glycerol raised the a-glycerophosphate levels to a greater extent in the male than in the female. In all cases, hepatocytes synthesized lipids at a faster rate from glycerol than from fructose. Glucose was incorporated into lipid at a slower rate than either of the other substrates.

<p> Maternal high fat (HF) intake before and/or during pregnancy increases female offsprings&rsquo; mammary cancer risk in several preclinical models. Here I studied if maternal HF intake during pregnancy cause transgenerational increase in mammary cancer risk, and if the increase is reversible by treating adult offspring with inhibitors of histone deacetylases (HDAC) or DNA methyltransferases (DNMT).</p><p> Pregnant C57BL/6NTac mice were fed either a diet high in n-6 polyunsaturated fatty acids (HF) or control diet (CON). HF diet was given from gestational day (GD) 10 &ndash; 20 to target fetal primordial germ cell formation and differentiation to germ cells. Offspring in subsequent F1-F3 generations were only fed CON diet. Mammary tumor incidence, induced by 7,12-dimethylbenz[a]anthracene (DMBA), was significantly higher in F1 and F3 HF offspring, than in the controls. Tumor latency was shorter and burden higher in F1 HF, with similar trends, though not statistically significant, in F3 HF.</p><p> RNA-sequencing of normal mammary glands revealed 1587 and 4423 differentially expressed genes between HF and CON offspring in F1 and F3, respectively, of which 48 genes were similarly altered in both generations. Ingenuity Pathway Analysis identified genes associated with Notch signaling as key alterations in HF mammary glands. Knowledge-fused Differential Dependency Network analysis identified 10 node genes in HF offspring uniquely connected to genes linked to increased cancer risk, therapy resistance, poor prognosis, and impaired anti-cancer immunity.</p><p> Next, I studied whether HDAC and DNMT inhibitor treatment in adulthood of the offspring, prior to tumor formation, could reverse the increased mammary cancer risk caused by <i>in utero</i> HF exposure. CON and HF offspring were given valproic acid and hydralazine in drinking water (epi-treatment), starting one week after tumor initiation by DMBA. Epi-treatment significantly decreased tumor burden in HF offspring, potentially through reactivation of silenced tumor suppressors <i>CLCA1</i> and <i>CDKN2A</i>, but adversely affected CON offspring. These adverse effects were linked to upregulation of PERK, p62 and HIF-1&alpha; in CON.</p><p> In summary, maternal HF intake during pregnancy induced transgenerational increase in offsprings&rsquo; mammary cancer risk, causes persistent changes in the expression of genes linked to increased breast cancer risk, and epi-treatment in adulthood may reduce this risk.</p>

The number of women participating in resistance training has increased from 14.4% in 1994 to 21.0% in 2010 (418). Resistance training is known to enhance body composition (20); however, the effects of an acute bout of resistance exercise (RE) on subcutaneous abdominal adipose tissue (SCAAT) glycerol release (lipolysis) and whole-body substrate utilization have only been documented in men (272). In fact, both RE and protein (alone and in combination) have been shown to improve lipolysis and fat oxidation leading to improved overall body composition (20). Mounting evidence suggests there are metabolic benefits of pre-sleep protein (PRO) consumption (65, 101, 190, 193, 274, 276). However, only one study directly assessed the effects of pre-sleep PRO consumption on SCAAT lipolysis and whole-body substrate utilization, and it was performed in overweight/obese men (190). Furthermore, few pre-sleep PRO studies to date have been directly compared to PRO consumed at other times of the day (17). Thus, it is difficult to interpret if the benefit is from pre-sleep feeding or simply increased daily PRO intake. PURPOSE: Therefore, the purpose of the current study was to assess the effects of RE (Aim 1) and pre-sleep versus daytime PRO consumption (Aim 2) on SCAAT lipolysis and whole-body substrate utilization in resistance-trained women. For Aim 1, a one-way ANOVA was used to analyze changes in interstitial GLY concentrations, metabolic rate, and plasma biomarkers around RE compared to baseline (BL) (BL, Mid-RE, post-RE). For Aim 2, a repeated measures ANOVA was used to compare the differences in interstitial GLY concentrations, metabolic rate, and plasma biomarkers between PRO-PLA and PLA-PRO conditions. If a significant finding was noted, a Tukey HSD post-hoc analysis was used to locate where the difference existed. Data were analyzed using SPSS (Version 25) with significance set at p<0.05, and are presented as mean ± standard error (SE). METHODS: Thirteen healthy, resistance-trained, eumenorrheic women (age, 22±3 years) volunteered to participate in the study. Participants reported to the laboratory on five occasions: pre-testing and familiarization of maximal testing (Visit 1), maximal testing (Visit 2), familiarization (Visit 3), and two experimental visits (Visits 4 and 5). For each of the experimental visits, participants came to the laboratory in a fasted state, and microdialysis probes were inserted into the SCAAT to measure lipolysis. Participants then performed a full-body RE session consisting of the following exercises in this order: squat, bench press, Romanian deadlift, bent-over row, shoulder press, reverse lunges. After RE on each of the experimental visit days, participants were randomized to consume either daytime PRO (30 grams of casein protein) 30 minutes post-RE and pre-sleep non-caloric, sensory-matched placebo (PLA, 0 grams of casein protein) (PRO-PLA), or daytime PLA and pre-sleep PRO (PLA-PRO), switching the order of the supplements on the following visit. Participants slept in the laboratory for overnight assessment of lipolysis and dietary intake was controlled by providing participants with breakfast, lunch and dinner (Vale Food Inc., Tallahassee, FL) based on their calculated caloric needs. Resting energy expenditure (REE) and respiratory exchange ratio (RER) were measured at baseline, post-RE, post pre-sleep supplement and the next morning of PLA-PRO and PRO-PLA conditions. Fasted blood samples were collected from the antecubital vein on three occasions for Aim 1: 1) baseline, 2) mid-RE, and 3) post-RE. In addition, blood samples were collected on three occasions for Aim 2: 1) 30 minutes after the daytime supplement (fed); 2) 30 minutes after the pre-sleep supplement (fed), and; 3) the next morning (fasted). Non-esterified fatty acids (NEFA), glycerol, glucose, and insulin were measured for Aim 1 and 2, while catecholamines (CATs) and growth hormone (GH) were measured only for Aim 1. RESULTS: After RE, REE (baseline: 1554±193; post-RE 1772±257 kcal/d; p=0.001) and fat oxidation (FatOx) (baseline: 5.64±0.23; post-RE: 7.57±0.34 g/hr; p<0.001) significantly increased (Aim 1, n=13). Additionally, SCAAT interstitial glycerol concentration was significantly higher at mid-RE (1177.4±667.1 µM, p=0.049) and post-RE (1197.3±1063.4 µM, p=0.01), compared to baseline (596.7±452.3 µM) (n=13). There were no significant changes in plasma biomarkers NEFA, glycerol, glucose, insulin, CATs, or GH. There was a significant increase in REE in both groups compared to baseline but no difference between groups. There was a significant increase in FatOx in PLA-PRO only after consuming the nighttime supplement (baseline: 5.64±0.23 g/min; PLA-PRO: 6.59±0.32 g/min, p=0.02), but no differences between PLA-PRO and PRO-PLA conditions. There were no other differences in lipolysis, metabolic measures, or plasma biomarkers between PRO-PLA or PLA-PRO conditions. RE increased lipolysis and FatOx mid-RE and post-RE in resistance-trained women. There were no differences in fat metabolism throughout sleep between PLA-PRO and PRO-PLA. CONCLUSION: Our findings indicate that RE improves fat metabolism potentially mediated by increases in CATs and GH. Consuming daily PRO 30 min post-RE or 30-min pre-sleep has no additional influence on fat metabolism (does not blunt overnight lipolysis) in resistance-trained women. This study was supported by a research grant from Friesland Campina® and Dymatize® Nutrition. / A Dissertation submitted to the Department of Nutrition, Food and Exercise Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Spring Semester 2018. / April 4, 2018. / fat oxidation, lipolysis, microdialysis, nighttime eating, nighttime protein, resistance exercise / Includes bibliographical references. / Michael J. Ormsbee, Professor Directing Dissertation; Robert J. Contreras, University Representative; Jeong-Su Kim, Committee Member; Lynn B. Panton, Committee Member.

Thesis (Ed.M.)—Boston University

Neurons in the arcuate nucleus of the hypothalamus (ARH) play a central role in the regulation of body weight and energy homeostasis. ARH neurons directly sense nutrient and hormonal signals of energy availability from the periphery and relay this information to secondary nuclei targets, where signals of energy status are integrated to regulate behaviors related to food intake and energy expenditure. Transduction of signals related to energy status by Pro-opiomelanocortin (POMC) and Neuropeptide-Y/agouti-related protein (NPY/AgRP) neurons in the ARH exert opposing influences on secondary neurons in central circuits regulating energy balance. My thesis research focused on the developmental events regulating the differentiation and specification of cell fates in the ARH. My first project was designed to characterize the ontogeny of Pomc- and Npy-expressing neurons in the developing mediobasal hypothalamus (Chapter 2). These experiments led to the unexpected finding that during mid-gestation, Pomc is broadly expressed in the majority of newly-born ARH neurons, but is subsequently down-regulated during later stages of development as cells acquire a terminal cell identity. Moreover, these studies demonstrated that most immature Pomc-expressing progenitors subsequently differentiate into non-POMC neurons, including a subset of functionally distinct NPY/AgRP neurons. The second aspect of my work focused on characterizing Pomc-expressing precursors throughout the brain (Chapter 3). Similar to findings in Chapter 2, Pomc was broadly expressed in many aspects of the developing brain and subsequently down-regulated as cells further differentiated into non-Pomc terminal identities. In the CNS, the percentage of POMC neurons derived from Pomc-expressing precursors are marginal. These findings are of general importance to the field of energy homeostasis research, because many genetically targeted functional manipulations of POMC cells have been induced during early development, a time in which Pomc is expressed in many cells that will not persist into a POMC terminal identity. The off target consequences of these manipulations have yet to be considered. Our work will provide the foundational evidence for potential confounds of targeted genetic POMC manipulations and may help to explain some of the unexpected phenotypes that have arisin using a BAC transgenic Pomc-Cre reagent. My current research efforts are focused on elucidating the molecular mechanism regulating differentiation and cell fate specification in the ARH during gestation and the early postnatal period (Chapter 4). Consistent with the identification of Pomc transcriptional activity during embryogenesis, functional POMC-processing products (β-endorphin and α-melanocyte-stimulating hormone) are also detected in embryonic hypothalamic extracts (at embryonic day (E) 13.5 and E15.5, respectively). The presence of POMC processing poducts in the embryo, prior to the establishment of circuits regulating food intake, may be involved in the local differentiation events. Preliminary loss-of-function studies are underway to determine the role of POMC processing products in differentiation of hypothalamic terminal fates. Early results from this work indicate that both β-endorphin and α-melanocyte-stimulating hormone are critical to the differentiation of the Pomc lineage. The goal of this work is to define the developmental origins of critical components of neuronal circuits that determine body weight. Evidence in the literature supports that maternal signals influence these events, our studies may provide a means to the design of effective strategies to reduce transmission of signals that increase susceptibility to obesity in offspring.

Retinoids are important mediators of many physiological processes in the body, including vision, reproduction, embryonic development, immunity and bone growth. Thus, the storage and metabolism of retinoids in the body has immediate implications for the overall health and metabolic homeostasis of the animal. This thesis research focused on two retinoid metabolites: retinyl ester, the form in which retinoids are stored, and retinoic acid, the transcriptionally active retinoid metabolite. Approximately 70% of retinoid in the body is stored in the liver, and, of this fraction, 80-90% is stored in the hepatic stellate cell (HSC) lipid droplets as retinyl ester. These lipid droplets are a distinguishing feature of the HSC, and they have recently been proposed to be specialized organelles for the storage of retinoid based on their unique retinoid content and responsiveness to dietary retinoid status. It is also known that the ability to synthesize and store retinyl ester in HSCs is necessary for the presence of HSC lipid droplets. Interestingly, it is well established that, with the progression of liver disease in human patients, there is a progressive loss of total hepatic retinoid content. As hepatic disease progresses, the HSCs transition from a quiescent to an activated phenotype, accompanied by the loss of their lipid droplet and retinoid content. The ultimate goal of this dissertation was to further elucidate the factors that regulate HSC retinoid storage as retinyl esters in lipid droplets and to define the factors that regulate HSC lipid droplet genesis and dissolution. The first aim of this research was to investigate the heterogeneity of HSCs and their lipid droplets in healthy, uninjured liver. Our observations suggest that the HSC population in a healthy, uninjured liver is heterogeneous. One subset of the total HSC population, which expresses early markers of HSC activation, may be primed and ready for rapid response to acute liver injury. We show that these "pre-activated" HSCs have: (i) increased expression of typical markers of HSC activation; (ii) decreased retinyl ester levels, accompanied by reduced expression of the enzyme needed for hepatic retinyl ester synthesis (LRAT); (iii) decreased triglyceride levels; (iv) increased expression of genes associated with lipid catabolism; and (v) an increase in expression of the retinoid-catabolizing cytochrome, CYP2S1. The second aim of this research was to investigate HSC lipid droplet formation and maintenance in healthy, but genetically-modified liver: specifically, we studied HSC lipid droplets in the LRAT KO mouse model, a system where HSC lipid droplets do not form. Our findings indicate that there are not global differences in retinoid-related gene expression, suggesting that the formation and maintenance of HSC lipid droplets is likely regulated entirely by the synthesis and storage of retinyl ester and not by more profound changes in retinoid metabolism. Our data also shows that the LRAT KO HSCs have significant differences in expression of genes related to lipid metabolism; overall, lipid biosynthesis is down-regulated and lipid catabolism is up-regulated in LRAT KO HSCs, which likely contributes to the complete absence of lipid droplets in the HSCs of these animals. Importantly, we show for the first time, to our knowledge, that the lipid droplet-associated proteins may be post-transcriptionally regulated. A final aim of this research was to investigate HSC lipid droplet dissolution in HSC activation and hepatic fibrosis, systems where HSC lipid droplets form, but are subsequently lost. We employed two standard models of HSC activation, the in vivo model of carbon tetrachloride (CCl4) treatment and the in vitro model, the culture of purified HSCs on plastic cell culture dishes. Additionally, we studied the effects of hypervitaminosis A since there is evidence in the literature that dietary vitamin A toxicity can cause hepatic fibrosis. Our studies suggest that, despite being unable to synthesize and store retinyl ester in lipid droplets, LRAT KO mice are not more susceptible than WT to the development of diet- or chemically-induced hepatic fibrosis. We found that, while the culture of HSCs on plastic results in the typical hallmark events of HSC activation, including the upregulation of Col1a1, the decrease in retinyl ester and the loss of lipid droplets, it does not regulate gene expression as HSC activation does in vivo. Thus, all future studies on HSC activation and its effects on retinoid storage should be conducted in vivo. We also present preliminary data on the alterations in the lipidome of activated HSCs, specifically with regard to the potent lipid signaling molecules, endocannabinoids, sphingolipids and ceramides. Our findings allow us to hypothesize that endocannabinoids and sphingolipids may function in activated HSCs as mediators of apoptosis. Importantly, this study demonstrates the ability to detect these lipids in very small aliquots of in vivo-activated HSCs and provides a strong foundation upon which all future studies may be built.