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Annual Review of Nutrition - Volume 43, 2023
Volume 43, 2023
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A Conversation with James Ntambi
Vol. 43 (2023), pp. 1–23More LessAn interview with James M. Ntambi, professor of biochemistry and the Katherine Berns Van Donk Steenbock Professor in Nutrition, College of Agricultural and Life Sciences, at the University of Wisconsin–Madison, took place via Zoom in April 2022. He was interviewed by Patrick J. Stover, director of the Institute for Advancing Health through Agriculture and professor of nutrition and biochemistry and biophysics at Texas A&M University. Dr. James Ntambi is a true pioneer in the field of nutritional biochemistry. He was among the very first to discover and elucidate the role that diet and nutrients play in regulating metabolism through changes in the expression of metabolic genes, focusing on the de novo lipogenesis pathways. As an African immigrant from Uganda, his love of science and his life experiences in African communities suffering from severe malnutrition molded his scientific interests at the interface of biochemistry and nutrition. Throughout his career, he has been an academic role model, a groundbreaking nutrition scientist, and an educator. His commitment to experiential learning through the many study-abroad classes he has hosted in Uganda has provided invaluable context for American students in nutrition. Dr. Ntambi's passion for education and scientific discovery is his legacy, and the field of nutrition has benefited enormously from his unique perspectives and contributions to science that are defined by his scientific curiosity, his generosity to his students and colleagues, and his life experiences. The following is an edited transcript.
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The Multifunctional Family of Mammalian Fatty Acid–Binding Proteins
Vol. 43 (2023), pp. 25–54More LessFatty acid–binding proteins (FABPs) are small lipid-binding proteins abundantly expressed in tissues that are highly active in fatty acid (FA) metabolism. Ten mammalian FABPs have been identified, with tissue-specific expression patterns and highly conserved tertiary structures. FABPs were initially studied as intracellular FA transport proteins. Further investigation has demonstrated their participation in lipid metabolism, both directly and via regulation of gene expression, and in signaling within their cells of expression. There is also evidence that they may be secreted and have functional impact via the circulation. It has also been shown that the FABP ligand binding repertoire extends beyond long-chain FAs and that their functional properties also involve participation in systemic metabolism. This article reviews the present understanding of FABP functions and their apparent roles in disease, particularly metabolic and inflammation-related disorders and cancers.
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Osteocalcin: A Multifaceted Bone-Derived Hormone
Vol. 43 (2023), pp. 55–71More LessTogether, loss- and gain-of-function experiments have identified the bone-derived secreted molecule osteocalcin as a hormone with a broad reach in rodents and primates. Following its binding to one of three receptors, osteocalcin exerts a profound influence on various aspects of energy metabolism as well as steroidogenesis, neurotransmitter biosynthesis and thereby male fertility, electrolyte homeostasis, cognition, the acute stress response, and exercise capacity. Although this review focuses mostly on the regulation of energy metabolism by osteocalcin, it also touches on its other functions. Lastly, it proposes what could be a common theme between the functions of osteocalcin and between these functions and the structural functions of bone.
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Intestinal Amino Acid Transport and Metabolic Health
Vol. 43 (2023), pp. 73–99More LessAmino acids derived from protein digestion are important nutrients for the growth and maintenance of organisms. Approximately half of the 20 proteinogenic amino acids can be synthesized by mammalian organisms, while the other half are essential and must be acquired from the nutrition. Absorption of amino acids is mediated by a set of amino acid transporters together with transport of di- and tripeptides. They provide amino acids for systemic needs and for enterocyte metabolism. Absorption is largely complete at the end of the small intestine. The large intestine mediates the uptake of amino acids derived from bacterial metabolism and endogenous sources. Lack of amino acid transporters and peptide transporter delays the absorption of amino acids and changes sensing and usage of amino acids by the intestine. This can affect metabolic health through amino acid restriction, sensing of amino acids, and production of antimicrobial peptides.
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Causes and Clinical Sequelae of Riboflavin Deficiency
Vol. 43 (2023), pp. 101–122More LessRiboflavin, in its cofactor forms flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), plays fundamental roles in energy metabolism, cellular antioxidant potential, and metabolic interactions with other micronutrients, including iron, vitamin B6, and folate. Severe riboflavin deficiency, largely confined to low-income countries, clinically manifests as cheilosis, angular stomatitis, glossitis, seborrheic dermatitis, and severe anemia with erythroid hypoplasia. Subclinical deficiency may be much more widespread, including in high-income countries, but typically goes undetected because riboflavin biomarkers are rarely measured in human studies. There are adverse health consequences of low and deficient riboflavin status throughout the life cycle, including anemia and hypertension, that could contribute substantially to the global burden of disease. This review considers the available evidence on causes, detection, and consequences of riboflavin deficiency, ranging from clinical deficiency signs to manifestations associated with less severe deficiency, and the related research, public health, and policy priorities.
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Sources and Sinks of Serine in Nutrition, Health, and Disease
Vol. 43 (2023), pp. 123–151More LessAmino acid dysregulation has emerged as an important driver of disease progression in various contexts. l-Serine lies at a central node of metabolism, linking carbohydrate metabolism, transamination, glycine, and folate-mediated one-carbon metabolism to protein synthesis and various downstream bioenergetic and biosynthetic pathways. l-Serine is produced locally in the brain but is sourced predominantly from glycine and one-carbon metabolism in peripheral tissues via liver and kidney metabolism. Compromised regulation or activity of l-serine synthesis and disposal occurs in the context of genetic diseases as well as chronic disease states, leading to low circulating l-serine levels and pathogenesis in the nervous system, retina, heart, and aging muscle. Dietary interventions in preclinical models modulate sensory neuropathy, retinopathy, tumor growth, and muscle regeneration. A serine tolerance test may provide a quantitative readout of l-serine homeostasis that identifies patients who may be susceptible to neuropathy or responsive to therapy.
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Gluconeogenesis Flux in Metabolic Disease
Vol. 43 (2023), pp. 153–177More LessGluconeogenesis is a critical biosynthetic process that helps maintain whole-body glucose homeostasis and becomes altered in certain medical diseases. We review gluconeogenic flux in various medical diseases, including common metabolic disorders, hormonal imbalances, specific inborn genetic errors, and cancer. We discuss how the altered gluconeogenic activity contributes to disease pathogenesis using data from experiments using isotopic tracer and spectroscopy methodologies. These in vitro, animal, and human studies provide insights into the changes in circulating levels of available gluconeogenesis substrates and the efficiency of converting those substrates to glucose by gluconeogenic organs. We highlight ongoing knowledge gaps, discuss emerging research areas, and suggest future investigations. A better understanding of altered gluconeogenesis flux may ultimately identify novel and targeted treatment strategies for such diseases.
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Major Gaps in Understanding Dietary Supplement Use in Health and Disease
Vol. 43 (2023), pp. 179–197More LessPrecise dietary assessment is critical for accurate exposure classification in nutritional research, typically aimed at understanding how diet relates to health. Dietary supplement (DS) use is widespread and represents a considerable source of nutrients. However, few studies have compared the best methods to measure DSs. Our literature review on the relative validity and reproducibility of DS instruments in the United States [e.g., product inventories, questionnaires, and 24-h dietary recalls (24HR)] identified five studies that examined validity (n = 5) and/or reproducibility (n = 4). No gold standard reference method exists for validating DS use; thus, each study's investigators chose the reference instrument used to measure validity. Self-administered questionnaires agreed well with 24HR and inventory methods when comparing the prevalence of commonly used DSs. The inventory method captured nutrient amounts more accurately than the other methods. Reproducibility (over 3 months to 2.4 years) of prevalence of use estimates on the questionnaires was acceptable for common DSs. Given the limited body of research on measurement error in DS assessment, only tentative conclusions on these DS instruments can be drawn at present. Further research is critical to advancing knowledge in DS assessment for research and monitoring purposes.
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Nonalcoholic Fatty Liver Disease and Omega-3 Fatty Acids: Mechanisms and Clinical Use
Vol. 43 (2023), pp. 199–223More LessNonalcoholic fatty liver disease (NAFLD) is the most common chronic fatty liver disease worldwide, particularly in obese and type 2 diabetic individuals. Currently, there are no therapies for NAFLD that have been approved by the US Food and Drug Administration. Herein, we examine the rationale for using ω3 polyunsaturated fatty acids (PUFAs) in NAFLD therapy. This focus is based on the finding that NAFLD severity is associated with a reduction of hepatic C20–22 ω3 PUFAs. Because C20–22 ω3 PUFAs are pleiotropic regulators of cell function, loss of C20–22 ω3 PUFAs has the potential to significantly impact hepatic function. We describe NAFLD prevalence and pathophysiology as well as current NAFLD therapies. We also present evidence from clinical and preclinical studies that evaluated the capacity of C20–22 ω3 PUFAs to treat NAFLD. Given the clinical and preclinical evidence, dietary C20–22 ω3 PUFA supplementation has the potential to decrease human NAFLD severity by reducing hepatosteatosis and liver injury.
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The Role of Artificial Intelligence in Deciphering Diet–Disease Relationships: Case Studies
Vol. 43 (2023), pp. 225–250More LessModernization of society from a rural, hunter-gatherer setting into an urban and industrial habitat, with the associated dietary changes, has led to an increased prevalence of cardiometabolic and additional noncommunicable diseases, such as cancer, inflammatory bowel disease, and neurodegenerative and autoimmune disorders. However, while dietary sciences have been rapidly evolving to meet these challenges, validation and translation of experimental results into clinical practice remain limited for multiple reasons, including inherent ethnic, gender, and cultural interindividual variability, among other methodological, dietary reporting–related, and analytical issues. Recently, large clinical cohorts with artificial intelligence analytics have introduced new precision and personalized nutrition concepts that enable one to successfully bridge these gaps in a real-life setting. In this review, we highlight selected examples of case studies at the intersection between diet–disease research and artificial intelligence. We discuss their potential and challenges and offer an outlook toward the transformation of dietary sciences into individualized clinical translation.
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Current Knowledge About the Impact of Maternal and Infant Nutrition on the Development of the Microbiota–Gut–Brain Axis
Vol. 43 (2023), pp. 251–278More LessThe prenatal and early postnatal periods are stages during which dynamic changes and the development of the brain and gut microbiota occur, and nutrition is one of the most important modifiable factors that influences this process. Given the bidirectional cross talk between the gut microbiota and the brain through the microbiota–gut–brain axis (MGBA), there is growing interest in evaluating the potential effects of nutritional interventions administered during these critical developmental windows on gut microbiota composition and function and their association with neurodevelopmental outcomes. We review recent preclinical and clinical evidence from animal studies and infant/child populations. Although further research is needed, growing evidence suggests that different functional nutrients affect the establishment and development of the microbiota–gut–brain axis and could have preventive and therapeutic use in the treatment of neuropsychiatric disorders. Therefore, more in-depth knowledge regarding the effect of nutrition on the MGBA during critical developmental windows may enable the prevention of later neurocognitive and behavioral disorders and allow the establishment of individualized nutrition-based programs that can be used from the prenatal to the early and middle stages of life.
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Iron Homeostasis During Pregnancy: Maternal, Placental, and Fetal Regulatory Mechanisms
Vol. 43 (2023), pp. 279–300More LessPregnancy entails a large negative balance of iron, an essential micronutrient. During pregnancy, iron requirements increase substantially to support both maternal red blood cell expansion and the development of the placenta and fetus. As insufficient iron has long been linked to adverse pregnancy outcomes, universal iron supplementation is common practice before and during pregnancy. However, in high-resource countries with iron fortification of staple foods and increased red meat consumption, the effects of too much iron supplementation during pregnancy have become a concern because iron excess has also been linked to adverse pregnancy outcomes. In this review, we address physiologic iron homeostasis of the mother, placenta, and fetus and discuss perturbations in iron homeostasis that result in pathological pregnancy. As many mechanistic regulatory systems have been deduced from animal models, we also discuss the principles learned from these models and how these may apply to human pregnancy.
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The Placenta: A Maternofetal Interface
Vol. 43 (2023), pp. 301–325More LessThe placenta is the gatekeeper between the mother and the fetus. Over the first trimester of pregnancy, the fetus is nourished by uterine gland secretions in a process known as histiotrophic nutrition. During the second trimester of pregnancy, placentation has evolved to the point at which nutrients are delivered to the placenta via maternal blood (hemotrophic nutrition). Over gestation, the placenta must adapt to these variable nutrient supplies, to alterations in maternal physiology and blood flow, and to dynamic changes in fetal growth rates. Numerous questions remain about the mechanisms used to transport nutrients to the fetus and the maternal and fetal determinants of this process. Growing data highlight the ability of the placenta to regulate this process. As new technologies and omics approaches are utilized to study this maternofetal interface, greater insight into this unique organ and its impact on fetal development and long-term health has been obtained.
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Malnourished Microbes: Host–Microbiome Interactions in Child Undernutrition
Vol. 43 (2023), pp. 327–353More LessChildhood undernutrition is a major global health burden that is only partially resolved by nutritional interventions. Both chronic and acute forms of child undernutrition are characterized by derangements in multiple biological systems including metabolism, immunity, and endocrine systems. A growing body of evidence supports a role of the gut microbiome in mediating these pathways influencing early life growth. Observational studies report alterations in the gut microbiome of undernourished children, while preclinical studies suggest that this can trigger intestinal enteropathy, alter host metabolism, and disrupt immune-mediated resistance against enteropathogens, each of which contribute to poor early life growth. Here, we compile evidence from preclinical and clinical studies and describe the emerging pathophysiological pathways by which the early life gut microbiome influences host metabolism, immunity, intestinal function, endocrine regulation, and other pathways contributing to child undernutrition. We discuss emerging microbiome-directed therapies and consider future research directions to identify and target microbiome-sensitive pathways in child undernutrition.
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Role of Diet–Microbiome Interaction in Gastrointestinal Disorders and Strategies to Modulate Them with Microbiome-Targeted Therapies
Vol. 43 (2023), pp. 355–383More LessDiet is an important determinant of health and consequently is often implicated in the development of disease, particularly gastrointestinal (GI) diseases, given the high prevalence of meal-related symptoms. The mechanisms underlying diet-driven pathophysiology are not well understood, but recent studies suggest that gut microbiota may mediate the effect of diet on GI physiology. In this review, we focus primarily on two distinct GI diseases where the role of diet has been best studied: irritable bowel syndrome and inflammatory bowel disease. We discuss how the concurrent and sequential utilization of dietary nutrients by the host and gut microbiota determines the eventual bioactive metabolite profiles in the gut and the biological effect of these metabolites on GI physiology. We highlight several concepts that can be gleaned from these findings, such as how distinct effects of an individual metabolite can influence diverse GI diseases, the effect of similar dietary interventions on multiple disease states, and the need for extensive phenotyping and data collection to help make personalized diet recommendations.
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Precision Nutrition: The Hype Is Exceeding the Science and Evidentiary Standards Needed to Inform Public Health Recommendations for Prevention of Chronic Disease
Vol. 43 (2023), pp. 385–407More LessAs dietary guidance for populations shifts from preventing deficiency disorders to chronic disease risk reduction, the biology supporting such guidance becomes more complex due to the multifactorial risk profile of disease and inherent population heterogeneity in the diet–disease relationship. Diet is a primary driver of chronic disease risk, and population-based guidance should account for individual responses. Cascading effects on evidentiary standards for population-based guidance are not straightforward. Precision remains a consideration for dietary guidance to prevent deficiency through the identification of population subgroups with unique nutritional needs. Reducing chronic disease through diet requires greater precision in (a) establishing essential nutrient needs throughout the life cycle in both health and disease; (b) considering effects of nutrients and other food substances on metabolic, immunological, inflammatory, and other physiological responses supporting healthy aging; and (c) considering healthy eating behaviors. Herein we provide a template for guiding population-based eating recommendations for reducing chronic diseases in heterogenous populations.
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Assessing and Monitoring Nutrition Security to Promote Healthy Dietary Intake and Outcomes in the United States
Vol. 43 (2023), pp. 409–429More LessThe US Department of Agriculture's Economic Research Service leads the federal government in data development and research on food security in US households. Nutrition security is an emerging concept that, although closely related, is distinct from food security. No standard conceptualization or measure of nutrition security currently exists. We review the existing research on nutrition security and how it is informed by the more robust literature on food security and diet quality. Based on this review, we propose a conceptual framework for understanding nutrition security and its relationship to food security. We identify two constructs (healthy diets and nutritional status) and multiple subconstructs that form the basis of nutrition security. The proposed framework and corresponding constructs are intended to provide (a) understanding of how nutrition security arises and how it differs from food security, (b) background on why assessment and monitoring of nutrition security is important, and (c) guidance for a research agenda that will further clarify the meaning of nutrition security and its measurement.
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Previous Volumes
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Volume 44 (2024)
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Volume 43 (2023)
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Volume 42 (2022)
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Volume 41 (2021)
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Volume 40 (2020)
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Volume 39 (2019)
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Volume 38 (2018)
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Volume 37 (2017)
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Volume 36 (2016)
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Volume 35 (2015)
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Volume 34 (2014)
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Volume 33 (2013)
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Volume 32 (2012)
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Volume 31 (2011)
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Volume 30 (2010)
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Volume 29 (2009)
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Volume 28 (2008)
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Volume 27 (2007)
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Volume 26 (2006)
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Volume 25 (2005)
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Volume 24 (2004)
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Volume 23 (2003)
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Volume 22 (2002)
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Volume 21 (2001)
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Volume 20 (2000)
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Volume 19 (1999)
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Volume 18 (1998)
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Volume 17 (1997)
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Volume 16 (1996)
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Volume 15 (1995)
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Volume 14 (1994)
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Volume 13 (1993)
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Volume 12 (1992)
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Volume 11 (1991)
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Volume 10 (1990)
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Volume 9 (1989)
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Volume 8 (1988)
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Volume 7 (1987)
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Volume 6 (1986)
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Volume 5 (1985)
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Volume 4 (1984)
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Volume 3 (1983)
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Volume 2 (1982)
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Volume 1 (1981)
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Volume 0 (1932)