50 years of metabolism research at Cell.

This 50th Anniversary Focus on Metabolism highlights several foundational and current themes of interest in metabolism research.

Metabolism in the spotlight: Dr. Giles Yeo on the impact and challenges of science communication.

In this interview with Cell, Dr. Giles Yeo shares his journey into metabolism research, his strategies for engaging audiences, and the challenges of simplifying complex concepts. He also discusses the impact of social media, the advantages of podcasting, and the question he's most afraid of.

American Society for Gastrointestinal Endoscopy­European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity

This joint ASGE-ESGE guideline provides an evidence-based summary and recommendations regarding the role of endoscopic bariatric and metabolic therapies (EBMTs) in the management of obesity. The document was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. It evaluates the efficacy and safety of EBMT devices and procedures that currently have CE mark or FDA-clearance/approval, or that had been approved within five years of document development. The guideline suggests the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity. Furthermore, it suggests the utilization of intragastric balloons and devices for endoscopic gastric remodeling (EGR) in conjunction with lifestyle modification for this patient population.

Transgender health objectives of training for adult Endocrinology and Metabolism programs: Outcomes of a modified-Delphi study.

BACKGROUND: Transgender people encounter significant barriers when seeking timely, high-quality healthcare, resulting in unmet medical needs with increased rates of diabetes, asthma, chronic obstructive pulmonary disease, and HIV. The paucity of postgraduate medical education to invest in standardization of transgender health training sustains these barriers, leaving physicians feeling unprepared and averse to provide transgender health care. Closing this education gap and improving transgender healthcare necessitates the development of consensus-built transgender health objectives of training (THOOT), particularly in Adult Endocrinology and Metabolism Residency programs. METHODS: We conducted a two-round modified-Delphi process involving a nationally representative panel of experts, including Adult Endocrinology and Metabolism program directors, physician content experts, residents, and transgender community members, to identify THOOT for inclusion in Canadian Endocrinology and Metabolism Residency programs. Participants used a 5-point Likert scale to assess THOOT importance for curricular inclusion, with opportunities for written feedback. Data was collected through Qualtrics and analyzed after each round. FINDINGS: In the first Delphi round, panelists reviewed and rated 81 literature extracted THOOT, achieving consensus on all objectives. Following panelists' feedback, 5 THOOT were added, 9 removed, 34 consolidated into 12 objectives, and 47 were rephrased or retained. In the second Delphi round, panelists assessed 55 THOOT. Consensus was established for 8 THOOT. Program directors' post-Delphi feedback further consolidated objectives to arrive at 4 THOOT for curriculum inclusion. CONCLUSIONS: To our knowledge, this is the first time a consensus-based approach has been used to establish THOOT for any subspecialty postgraduate medicine program across Canada or the United States. Our results lay the foundation towards health equity and social justice in transgender health medical education, offering a blueprint for future innovations.

Effects of Hibiscus sabdariffa supplementation on metabolism and bladder in obese rats

Purpose: Hibiscus sabdariffa (HS) extract has several health benefits and anti-obesogenic effects. The aim of the present study was to assess whether the medicinal properties attributable to HS would prevent or mitigate bladder changes induced by obesity in an experimental model. Methods: Forty-eight male Wistar rats were submitted to one of four different dietary interventions (12 animals each): G1, standard diet and water (controls); G2, standard diet and HS tea; G3, a palatable high-fat diet and water; and G4, high-fat diet diet and HS tea. The animals were monitored for body weight, feed, and water and tea intake, according to the allocated group. After 16 weeks, the animals were euthanized, and the levels of creatinine, inflammatory cytokines, testosterone, cholesterol, triglycerides, and electrolytes were evaluated. In addition, histopathological analysis of the animals' bladder was performed. Results: Groups receiving HS (G2 and G4) showed decreased levels of the pro-inflammatory cytokine interleukin-1α. HS tea was able to reduce low-density lipoprotein and triglyceride levels in the G2 group compared to other groups. Only in the G3 there was a significant increase in the body weight when it was compared the 12th and 16th weeks. Leptin was shown to be elevated in the groups that received a high-fat diet. There was a significant decrease in the muscle fibers thickness and in the total collagen count in G4 bladder when compared with G1 and G3. Conclusions: HS has an anti-inflammatory role, can reverse hyperlipidemia in rats, and reduced deleterious effects of obesity on these animals' bladder.

Genética y genómica de la longevidad y el envejecimiento / Genetics and genomics of longevity and aging

El envejecimiento y la longevidad son procesos que involucran una serie de factores genéticos, bioquímicos y ambientales. En esta revisión se tratan algunas cuestiones sobre estos dos procesos biológicos y epigenéticos. Se presentan los genes más importantes en estos procesos, así como se ejemplifican enfermedades que presentan un aceleramiento o falla en la longevidad y el envejecimiento. Se usa el análisis inteligente de datos para hallar interacciones de proteínas/genes que expliquen estos dos fenómenos biológicos.

Aging and longevity are processes that involve a series of genetic, biochemical and environmental factors. This review addresses some issues about these two biological and epigenetic processes. The most important genes in these processes are presented, as well as diseases that present an acceleration or failure in longevity and aging. Intelligent data analysis is used to find protein/gene interactions that explain these two biological phenomena.

Weight and metabolic changes in early psychosis-association with daily quantification of medication exposure during the first hospitalization.

BACKGROUND: The most common causes of death in schizophrenia are cardiovascular disorders, which are closely related to metabolic syndrome/obesity. To better understand the development of metabolic alterations early in the course of illness, we quantified daily medication exposure in the first days of the first hospitalization for psychosis and related it to changes in weight and metabolic markers. STUDY DESIGN: We recruited participants with first episode psychosis (FEP, N = 173) during their first psychiatric hospitalization and compared them to controls (N = 204). We prospectively collected weight, body mass index, metabolic markers, and exact daily medication exposure at admission and during hospitalization. STUDY RESULTS: Individuals with FEP gained on average 0.97 ± 2.26 BMI points or 3.46 ± 7.81 kg of weight after an average of 44.6 days of their first inpatient treatment. Greater antipsychotic exposure was associated with greater BMI increase, but only in people with normal/low baseline BMI. Additional predictors of weight gain included type of medication and duration of treatment. Medication exposure was not directly related to metabolic markers, but higher BMI was associated with higher TGC, TSH, and lower HDL. Following inpatient treatment, participants with FEP had significantly higher BMI, TGC, prolactin, and lower fT4, HDL than controls. CONCLUSION: During their first admission, people with FEP, especially those with normal/low baseline BMI, showed a rapid and clinically significant weight increase, which was associated with exposure to antipsychotics, and with metabolic changes consistent with metabolic syndrome. These findings emphasize weight monitoring in FEP and suggest a greater need for caution when prescribing metabolically problematic antipsychotics to people with lower BMI.

Linear Response Theory of Evolved Metabolic Systems.

Predicting cellular metabolic states is a central problem in biophysics. Conventional approaches, however, sensitively depend on the microscopic details of individual metabolic systems. In this Letter, we derived a universal linear relationship between the metabolic responses against nutrient conditions and metabolic inhibition, with the aid of a microeconomic theory. The relationship holds in arbitrary metabolic systems as long as the law of mass conservation stands, as supported by extensive numerical calculations. It offers quantitative predictions without prior knowledge of systems.

Ancestry-driven metabolite variation provides insights into disease states in admixed populations.

BACKGROUND: Metabolic pathways are related to physiological functions and disease states and are influenced by genetic variation and environmental factors. Hispanics/Latino individuals have ancestry-derived genomic regions (local ancestry) from their recent admixture that have been less characterized for associations with metabolite abundance and disease risk. METHODS: We performed admixture mapping of 640 circulating metabolites in 3887 Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Replication was performed in 1856 nonoverlapping HCHS/SOL participants with metabolomic data. RESULTS: By leveraging local ancestry, this study identified significant ancestry-enriched associations for 78 circulating metabolites at 484 independent regions, including 116 novel metabolite-genomic region associations that replicated in an independent sample. Among the main findings, we identified Native American enriched genomic regions at chromosomes 11 and 15, mapping to FADS1/FADS2 and LIPC, respectively, associated with reduced long-chain polyunsaturated fatty acid metabolites implicated in metabolic and inflammatory pathways. An African-derived genomic region at chromosome 2 was associated with N-acetylated amino acid metabolites. This region, mapped to ALMS1, is associated with chronic kidney disease, a disease that disproportionately burdens individuals of African descent. CONCLUSIONS: Our findings provide important insights into differences in metabolite quantities related to ancestry in admixed populations including metabolites related to regulation of lipid polyunsaturated fatty acids and N-acetylated amino acids, which may have implications for common diseases in populations.

Systemwide effects of ER-intracellular membrane contact site disturbance in primary endothelial cells.

Membrane contact sites (MCS) make up a crucial route of inter-organelle non-vesicular transport within the cell. Multiple proteins are involved in this process, which includes the ER-resident proteins vesicle associated membrane protein associated protein A and -B (VAPA/B) that form MCS between the ER and other membrane compartments. Currently most functional data on VAP depleted phenotypes have shown alterations in lipid homeostasis, induction of ER stress, dysfunction of UPR and autophagy, as well as neurodegeneration. Literature on concurrent silencing of VAPA/B is still sparse; therefore, we investigated how it affects the macromolecule pools of primary endothelial cells. Our transcriptomics results showed significant upregulation in genes related to inflammation, ER and Golgi dysfunction, ER stress, cell adhesion, as well as Coat Protein Complex-I and -II (COP-I, COP-II) vesicle transport. Genes related to cellular division were downregulated, as well as key genes of lipid and sterol biosynthesis. Lipidomics analyses revealed reductions in cholesteryl esters, very long chain highly unsaturated and saturated lipids, whereas increases in free cholesterol and relatively short chain unsaturated lipids were evident. Furthermore, the knockdown resulted in an inhibition of angiogenesis in vitro. We speculate that ER MCS depletion has led to multifaceted outcomes, which include elevated ER free cholesterol content and ER stress, alterations in lipid metabolism, ER-Golgi function and vesicle transport, which have led to a reduction in angiogenesis. The silencing also induced an inflammatory response, consistent with upregulation of markers of early atherogenesis. To conclude, ER MCS mediated by VAPA/B play a crucial role in maintaining cholesterol traffic and sustain normal endothelial functions.

A Conversation with James Ntambi.

An 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.

Systems Immunology Approaches to Metabolism.

Over the last decade, immunometabolism has emerged as a novel interdisciplinary field of research and yielded significant fundamental insights into the regulation of immune responses. Multiple classical approaches to interrogate immunometabolism, including bulk metabolic profiling and analysis of metabolic regulator expression, paved the way to appreciating the physiological complexity of immunometabolic regulation in vivo. Studying immunometabolism at the systems level raised the need to transition towards the next-generation technology for metabolic profiling and analysis. Spatially resolved metabolic imaging and computational algorithms for multi-modal data integration are new approaches to connecting metabolism and immunity. In this review, we discuss recent studies that highlight the complex physiological interplay between immune responses and metabolism and give an overview of technological developments that bear the promise of capturing this complexity most directly and comprehensively.

Caloric restriction remodels the hepatic chromatin landscape and bile acid metabolism by modulating the gut microbiota.

BACKGROUND: Caloric restriction (CR) has been known to promote health by reprogramming metabolism, yet little is known about how the epigenome and microbiome respond during metabolic adaptation to CR. RESULTS: We investigate chromatin modifications, gene expression, as well as alterations in microbiota in a CR mouse model. Collectively, short-term CR leads to altered gut microbial diversity and bile acid metabolism, improving energy expenditure. CR remodels the hepatic enhancer landscape at genomic loci that are enriched for binding sites for signal-responsive transcription factors, including HNF4α. These alterations reflect a dramatic reprogramming of the liver transcriptional network, including genes involved in bile acid metabolism. Transferring CR gut microbiota into mice fed with an obesogenic diet recapitulates the features of CR-related bile acid metabolism along with attenuated fatty liver. CONCLUSIONS: These findings suggest that CR-induced microbiota shapes the hepatic epigenome followed by altered expression of genes responsible for bile acid metabolism.

Seminars in immunology special issue: Nutrition, microbiota and immunity The unexplored microbes in health and disease.

Functional characterization of the microbiome's influence on host physiology has been dominated by a few characteristic example strains that have been studied in detail. However, the extensive development of methods for high-throughput bacterial isolation and culture over the past decade is enabling functional characterization of the broader microbiota that may impact human health. Characterizing the understudied majority of human microbes and expanding our functional understanding of the diversity of the gut microbiota could enable new insights into diseases with unknown etiology, provide disease-predictive microbiome signatures, and advance microbial therapeutics. We summarize high-throughput culture-dependent platforms for characterizing bacterial strain function and host-interactions. We elaborate on the importance of these technologies in facilitating mechanistic studies of previously unexplored microbes, highlight new opportunities for large-scale in vitro screens of host-relevant microbial functions, and discuss the potential translational applications for microbiome science.

Evolution of Henrik Kacser's thought: Early publications on the organization of the whole system.

Although the papers of Kacser and Burns (1973) and Heinrich and Rapoport (1974a,b) are commonly taken as the birth of metabolic control analysis, many of the ideas in them are foreshadowed in earlier papers, from 1956 onwards, when Kacser first argued for taking a systemic view of genetics and biochemistry.

Transtornos alimentares: vivências de mulheres acima de 30 anos / Eating disorders: experiences of women aged over 30 years / Trastornos alimentarios: experiencias de mujeres de más de 30 años

O objetivo deste estudo foi compreender como mulheres adultas (acima de 30 anos) diagnosticadas com transtornos alimentares (TAs) vivenciam o adoecer. Trata-se de um estudo qualitativo, descritivo e exploratório, desenvolvido com base no referencial teórico-metodológico da Análise Fenomenológica Interpretativa (AFI). Participaram seis mulheres, com idades entre 34 e 65 anos, atendidas em um serviço especializado. Os dados foram coletados por meio de entrevista aberta, de inspiração fenomenológica, na modalidade remota. As entrevistas foram audiogravadas, transcritas e analisadas seguindo os passos da AFI. Duas categorias temáticas foram identificadas: "Vivendo antes do adoecer" e "Encontrando-se doente." Constatou-se que os sintomas tiveram início anteriormente à vida adulta e que houve dificuldade na confirmação do diagnóstico. Na perspectiva das participantes, conviver com a sintomatologia ficou mais complicado em função de particularidades de manejo dos sintomas na vida adulta, e a idade é percebida como um fator que impacta e dificulta ainda mais a recuperação. As participantes relataram desesperança em relação ao futuro, apesar de a maioria reconhecer melhoras no quadro clínico ao longo do tempo e de valorizar a relação de confiança estabelecida com a equipe multiprofissional.(AU)

This study aimed to understand the experience of illness of adult women (over 30 years) diagnosed with eating disorders (ED). This is a qualitative, descriptive, and exploratory study, using Interpretative Phenomenological Analysis (IPA) as theoretical and methodological framework. A sample of six women aged 34-64 years, assisted in a specialized service, were recruited to complete a phenomenological in-depth open interview. The data were remotely collected. Interviews were audio-recorded, transcribed and analyzed following the IPA. Two thematic categories were identified: "Living before the illness" and "Finding about the illness." It was found that the symptoms started before adulthood and that there was difficulty establishing the diagnosis. Living with the symptoms became more complicated due to particularities of symptom management in adulthood and age is perceived as a factor that impacts recovery and makes it even more difficult. The participants reported hopelessness about the future, although most recognized improvements in the clinical condition over time and valued the trusting relationship they established with the multiprofessional team.(AU)

El objetivo de este estudio fue comprender las experiencias de las mujeres adultas (mayores de 30 años) diagnosticadas con trastornos alimentarios (TA) respecto a la enfermedad. Se trata de un estudio cualitativo, descriptivo y exploratorio, desarrollado a partir del marco teórico y metodológico del Análisis Fenomenológico Interpretativo (AFI). Participaron seis mujeres, con edades de entre 34 y 65 años, atendidas en un servicio especializado. Los datos se recogieron mediante entrevistas abiertas, de inspiración fenomenológica, en la modalidad a distancia. Las entrevistas fueron grabadas en audio, transcritas y analizadas siguiendo los pasos del AFI. Se identificaron dos categorías temáticas: "Vivir antes de enfermar" y "Encontrarse enfermo." Se constató que los síntomas comenzaron antes de la edad adulta y que hubo dificultades de establecer el diagnóstico. La convivencia con síntomas se complicó debido a las particularidades del manejo de los síntomas en la vida adulta y la edad se percibe como un factor que influye y dificulta aún más la recuperación. Los participantes manifestaron desesperanza sobre el futuro, aunque reconocieron mejoras en el cuadro clínico con el paso del tiempo y valoraron la relación de confianza establecida con el equipo multiprofesional.(AU)