Tryptophan (Trp) metabolism is linked to health and disease, with indoleamine 2,3-dioxygenase 1 (IDO) being a key enzyme in its breakdown outside the liver. This process produces metabolites that influence metabolic and inflammatory responses. A distinctive feature of the gut is its involvement in three major Trp catabolic pathways: the IDO-driven kynurenine pathway, bacteria-produced indoles, and

When acute SARS-CoV-2 infections cause symptoms that persist longer than 3 months, this condition is termed long COVID. Symptoms experienced by patients often include myalgia, fatigue, brain fog, cognitive impairments, and post-exertional malaise (PEM), which is the worsening of symptoms following mental or physical exertion. There is little consensus on the pathophysiology of exercise-induced PEM

Inter-organ communication (IOC) is a complex mechanism involved in maintaining metabolic homeostasis and healthy aging. Dysregulation of distinct forms of IOC is linked to metabolic derangements and age-related pathologies, implicating these processes as a potential target for therapeutic intervention to promote healthy aging. In this review, we delve into IOC mediated by hormonal signaling, circulating

Endothelial cells (ECs) form the inner lining of blood vessels that is crucial for vascular function and homeostasis. They regulate vascular tone, oxidative stress, and permeability. Dysfunction leads to increased permeability, leukocyte adhesion, and thrombosis. ECs undergo metabolic changes in conditions such as wound healing, cancer, atherosclerosis, and diabetes, and can influence disease progression

It has long been thought that the functional identity of mammalian brain neurons is programmed during development and remains stable throughout adult life; however, certain populations of neurons continue to express active regulators of neuronal identity into adulthood. Prolonged exposure to diet-induced metabolic stress induces features of neuronal identity modification in adult mice, and maladaptive

The incorporation of the glymphatic clearance system in the study of brain physiology aids in the advancement of innovative diagnostic and treatment strategies for neurological disorders. Exploring the glymphatic system across (from) neurological and (to) metabolic diseases may provide a better link between obesity and neurological disorders. Recent studies indicate the role of metabolic dysfunction

Lipid droplets (LDs) are dynamic organelles that communicate with other cellular components to orchestrate energetic homeostasis and signal transduction. In skeletal muscle, the presence and importance of LDs have been widely studied in myofibers of both rodents and humans under physiological conditions and in metabolic disorders. However, the role of LDs in myogenic stem cells has only recently begun

Obesity has become a global pandemic that is associated with a range of metabolic disorders. Traditional treatment options, such as lifestyle modification and anti-obesity medications, often exhibit limited efficacy and can lead to long-term weight gain, especially upon discontinuation of the medication. Although bariatric surgery is effective, its accessibility is constrained, and only a small percentage

The Genes & Health study, an initiative focused on British-Pakistani and British-Bangladeshi volunteers, is at the forefront of diversifying genetic research and driving scientific innovation. Here, we explore how this study has propelled scientific advancements and positively impacted communities, emphasizing its collaborative ethos, dedication to societal needs, and accomplishments.

Metabolic diseases, characterized by chronic low-grade inflammation, exhibit a compromised gut barrier allowing the translocation of bacteria-derived products to bloodstream and distant metabolic organs. Bacterial DNA can be detected in metabolic tissues during the onset of these diseases, highlighting its role in the development of metabolic diseases. Extracellular vesicles (EVs) are involved in the

Mitochondria must sense their environment to enable cells and organisms to adapt to diverse environments and survive during stress. However, during microbial infection, an evolutionary pressure since the inception of the eukaryotic cell, these organelles are traditionally viewed as targets for microbes. In this opinion we consider the perspective that mitochondria are domesticated microbes that sense

Paternal health and exposure to adverse environments in the period prior to conception have a profound impact on future generations. Adversities such as stress, diet, and toxicants influence offspring health. Emerging evidence indicates that epigenetic mechanisms including noncoding RNA, DNA methylation, and chromatin remodelling mediate these effects. Preclinical studies have contributed to advancing

Non-sugar sweeteners (NSS), low- or no-calorie alternatives to sugar, are marketed for weight loss and improved blood glucose control in people with diabetes. However, their health effects remain controversial. This review provides a brief overview of sweet taste perception and summarizes experimental findings of the impact of NSS on cardiometabolic health in animal models and humans. We also review

MicroRNAs (miRNAs) are noncoding RNA molecules that regulate gene expression post-transcriptionally and influence numerous biological processes. Aberrant miRNA expression is linked to diseases such as diabetes mellitus; indeed, miRNAs regulate pancreatic islet inflammation in both type 1 (T1D) and type 2 diabetes (T2D). Traditionally, miRNA research has focused on canonical sequences and offers a two-layer

Previously characterized as inert fat depots, adipocytes are now recognized as dynamic mediators of inflammatory tone, metabolic health, and nutrient homeostasis. As endocrine organs, specialized depots of adipose tissue engage in crosstalk between the gut, liver, pancreas, and brain to coordinate appetite, thermogenesis, and ultimately body weight. These functions are tightly linked to the inflammatory

Recent genetic studies have implicated an active role for intrahepatic lipid accumulation in the pathogenesis of both polycystic ovary syndrome (PCOS) and cardiovascular disease. These new insights may provide novel (non)pharmacological opportunities for the prevention and treatment of PCOS and cardiovascular disease at both the societal and clinical level.

Growth differentiation factor 15 (GDF15) is a member of the transforming growth factor-β (TGF-β) superfamily. Despite its identification over 20 years ago, the functions of GDF15 remain complex and not fully elucidated. Its concentration in plasma varies widely depending on the physiological and pathophysiological state of the organism. GDF15 has been described to regulate food intake and insulin sensitivity

Fatty acids (FAs) are essential nutrients that play multiple roles in cellular activities. To meet cell-specific needs, cells exhibit differential uptake of FAs in diverse physiological or pathological contexts, coordinating to maintain metabolic homeostasis. Cells tightly regulate the localization and transcription of CD36 and other key proteins that transport FAs across the plasma membrane in response

Five acyl-CoA synthetase long-chain family members (ACSLs) are responsible for catalyzing diverse long-chain fatty acids (LCFAs) into LCFA-acyl-coenzyme A (CoA) for their subsequent metabolism, including fatty acid oxidation (FAO), lipid synthesis, and protein acylation. In this review, we focus on ACSLs and their LCFA substrates and introduce their involvement in regulation of cancer proliferation

Health emerges from coordinated psychobiological processes powered by mitochondrial energy transformation. But how do mitochondria regulate the multisystem responses that shape resilience and disease risk across the lifespan? The Mitochondrial Stress, Brain Imaging, and Epigenetics (MiSBIE) study was established to address this question and determine how mitochondria influence the interconnected neuroendocrine

Two initiatives are reshaping how we can approach and address the persistent and widely prevalent challenge of malnutrition, the leading global risk factor for morbidity and mortality. First is the focus on precision nutrition to identify inter- and intra-individual variation in our responses to diet, and its determinants. Second is the Food is Medicine (FIM) approach, an umbrella term for programs

Health funding agencies are increasingly prioritizing equity, diversity, and inclusion (EDI) strategies. This shift, while essential, can inadvertently lead to 'helicopter research', especially among junior researchers, due to insufficient institutional support. We warn against such unethical practices and propose strategies for academia and funding bodies to address them.

Cancer presents a significant global public health challenge. Within the tumor microenvironment (TME), macrophages are the most abundant immune cell population. Tumor-associated macrophages (TAMs) undergo metabolic reprogramming through influence of the TME; thus, by manipulating key metabolic pathways such as glucose, lipid, or amino acid metabolism, it may be possible to shift TAMs towards an antitumor

Physiological changes during pregnancy may predict future cardiovascular and metabolic diseases; thus, identifying mechanisms driving cardiometabolic impairments, as well as potential interventions to improve health during pregnancy, is crucial. We discuss how sleep and circadian disruption during pregnancy and postpartum affect cardiometabolic risk, and identify future research directions.

Obesity is a major global health issue with various metabolic complications. Both bariatric surgery and dieting achieve weight loss and improve whole-body metabolism, but vary in their ability to maintain these improvements over time. Adipose tissue and skeletal muscle metabolism are crucial in weight regulation, and obesity is linked to mitochondrial dysfunction in both tissues. The impact of bariatric

Accurate assessment of brown fat thermogenesis by non-invasive means remains challenging. Writing in Nature Metabolism, Cai et al. leverage the futile creatine cycling characteristic of thermogenic adipocytes to show that a type of magnetic resonance imaging (MRI) technique sensitive to endogenous creatine levels faithfully tracks brown fat thermogenesis in rodents and in humans.

Aging is a major risk factor for a variety of diseases, thus, translation of aging research into practical applications is driven by the unmet need for existing clinical therapeutic options. Basic and translational research efforts are converging at a critical stage, yielding insights into how fundamental aging mechanisms are used to identify promising geroprotectors or therapeutics. This review highlights

Metformin, an oral antihyperglycemic drug that has been in use for over 60 years, remains a first-line therapy for type 2 diabetes (T2D). Numerous studies have suggested that metformin promotes health benefits beyond T2D management, including weight loss, cancer prevention and treatment, and anti-aging, through several proposed mechanistic targets. Here we discuss the established effects of metformin

Astrocytes, the predominant glial cell type in the mammalian brain, influence a wide variety of brain parameters including neuronal energy metabolism. Exciting recent studies have shown that obesity and diabetes can impact on astrocyte function. We review evidence that dysregulation of astrocytic lipid metabolism and glucose sensing contributes to dysregulation of whole-body energy balance, thermoregulation

Despite sharing incretin activity with glucagon-like peptide 1 (GLP-1), the development of gastric inhibitory polypeptide (GIP)-based drugs has been hindered by the minor effects of native GIP on appetite and body weight and genetic studies associating loss-of-function with reduced obesity. Yet, pharmacologically optimized GIP-based molecules have demonstrated profound weight lowering benefits of GIPR

Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme for redox reactions and regulates cellular catabolic pathways. An intertwined relationship exists between NAD+ and mitochondria, with consequences for mitochondrial function. Dysregulation in NAD+ homeostasis can lead to impaired energetics and increased oxidative stress, contributing to the pathogenesis of cardiometabolic diseases.

Very-low-density lipoprotein (VLDL), a triglyceride-rich lipoprotein secreted by hepatocytes, is pivotal for supplying peripheral tissues with fatty acids for energy production. As if walking on a tightrope, perturbations in the balance of VLDL metabolism contribute to cardiometabolic dysfunction, promoting pathologies such as cardiovascular disease (CVD) or metabolic dysfunction-associated steatotic

Liver diseases represent a growing global health challenge, and the increasing prevalence of obesity and metabolic disorders is set to exacerbate this crisis. To meet evolving regulatory demands, patient-specific in vitro liver models are essential for understanding disease mechanisms and developing new therapeutic approaches. Organoid models, which faithfully recapitulate liver biology, can be established

The widespread use of per- and polyfluoroalkyl substances (PFASs), and their resistance to degradation, renders human exposure to them inevitable. PFAS exposure disturbs endocrine function, potentially affecting cognitive development in newborns through thyroid dysfunction during pregnancy. Recent studies reveal varying male and female reproductive toxicity across PFAS classes, with alternative analogs

Glucocorticoids (GCs) are potent anti-inflammatory drugs. A new study by Auger et al. found that GCs increase itaconate, an anti-inflammatory tricarboxylic acid (TCA) cycle intermediate, by promoting movement of cytosolic pyruvate dehydrogenase (PDH) to mitochondria. Itaconate was sufficient for mediating the anti-inflammatory effects of GCs in mice, overriding the notion that nuclear glucocorticoid

Our limited understanding of metabolic aging poses major challenges to comprehending the diverse cellular alterations that contribute to age-related decline, and to devising targeted interventions. This review provides insights into the heterogeneous nature of cellular metabolism during aging and its response to interventions, with a specific focus on cellular heterogeneity and its implications. By

Triglyceride-rich lipoproteins (TRLs) play essential roles in human health and disease by transporting bulk lipids into the circulation. This review summarizes the fundamental mechanisms and diverse factors governing lipoprotein production, secretion, and regulation. Emphasizing the broader implications for human health, we outline the intricate landscape of lipoprotein research and highlight the potential

Individuals with excessive adipose tissue and type 2 diabetes mellitus (T2DM) face a heightened risk of cardiovascular morbidity and mortality. Metabolic surgery is an effective therapy for people with severe obesity to achieve significant weight loss. Additionally, metabolic surgery improves blood glucose levels and can lead to T2DM remission, reducing major adverse cardiovascular outcomes (MACE)

The success of disseminating cancer cells (DTCs) at specific metastatic sites is influenced by several metabolic factors. Even before DTCs arrival, metabolic conditioning from the primary tumor participates in creating a favorable premetastatic niche at distant organs. In addition, DTCs adjust their metabolism to better survive along the metastatic journey and successfully colonize their ultimate destination

Microplastics and nanoplastics (MNPs) are being recognized as new cardiovascular risk factors, impacting vascular cell functions and exacerbating atherosclerosis through diverse mechanisms. However, the varied concentrations of MNPs detected in major cardiovascular tissues highlight the urgent need for standardized research methodologies to better understand their impact and inform future health guidelines

Pregnancy is associated with physiological adaptations that affect virtually all organs, enabling the mother to support the growing fetus and placenta while withstanding the demands of pregnancy. As a result, mammalian pregnancy is a unique state that exerts paradoxical effects on maternal health. On one hand, the metabolic stress induced by pregnancy can accelerate aging and functional decline in

The tumor suppressor p53 regulates metabolic homeostasis. Recently, Tsaousidou et al. reported that selective activation of p53 via downregulation of Tudor interacting repair regulator (TIRR) confers protection against cancer despite obesity and insulin resistance, providing new insights into the role of p53 at the intersection of oncogenesis and systemic metabolism.

Eating behaviour and circadian rhythms are closely related. The type, timing, and quantity of food consumed, and host circadian rhythms, directly influence the intestinal microbiota, which in turn impacts host circadian rhythms and regulates food intake beyond homeostatic eating. This Opinion discusses the impact of food intake and circadian disruptions induced by an obesogenic environment on gut-brain

During the process of implantation, the embryo first attaches to the uterine epithelium and then invades the underlying stroma, resulting in the transformation of the stroma into a secretory tissue that surrounds the embryo. An intricate dialogue allows the developing embryo and the maternal tissue to be in constant communication with each other. In many mammals, including humans, embryo implantation

Axon regeneration requires the mobilization of intracellular resources, including proteins, lipids, and nucleotides. After injury, neurons need to adapt their metabolism to meet the biosynthetic demands needed to achieve axonal regeneration. However, the exact contribution of cellular metabolism to this process remains elusive. Insights into the metabolic characteristics of proliferative cells may

Autophagy is critical for energy homeostasis and the function of organelles such as endoplasmic reticulum (ER) and mitochondria. Dysregulated autophagy due to aging, environmental factors, or genetic predisposition can be an underlying cause of not only diabetes through β-cell dysfunction and metabolic inflammation, but also diabetic complications such as diabetic kidney diseases (DKDs). Dysfunction

The intestine is a proliferative tissue subjected to a variety of stresses that disturb its homeostasis. A recent study by demonstrated that loss of the tumor suppressor SIRT4 leads to increased cell proliferation via the nucleotide biosynthesis pathway over the salvage pathway after ionizing irradiation (IR).

The gut microbiota plays a crucial role in maintaining homeostasis and promoting health. A growing number of studies have indicated that gut microbiota can affect cancer development, prognosis, and treatment through their metabolites. By remodeling the tumor microenvironment and regulating tumor immunity, gut microbial metabolites significantly influence the efficacy of anticancer therapies, including

Dietary fiber is degraded by commensal gut microbes to yield host-beneficial short-chain fatty acids (SCFAs), but personalized responses to fiber supplementation highlight a role for other microbial metabolites in shaping host health. In this review we summarize recent findings from dietary fiber intervention studies describing health impacts attributed to microbial metabolites other than SCFAs, particularly

Central ceramides regulate energy metabolism by impacting hypothalamic neurons. This allows ceramides to integrate endocrine signals - such as leptin, ghrelin, thyroid hormones, or estradiol - and to modulate the central control of puberty. In this forum article we discuss recent evidence suggesting that specific ceramide species and neuronal populations are involved in these effects.

The presence of membrane-bound organelles with specific functions is one of the main hallmarks of eukaryotic cells. Organelle membranes are composed of specific lipids that govern their function and interorganelle communication. Discoveries in cell biology using imaging and omic technologies have revealed the mechanisms that drive membrane remodeling, organelle contact sites, and metabolite exchange

The gut microbiome can play a crucial role in hepatocellular carcinoma (HCC) progression through the enterohepatic circulation, primarily acting via metabolic reprogramming and alterations in the hepatic immune microenvironment triggered by microbe-associated molecular patterns (MAMPs), metabolites, and fungi. In addition, the gut microbiome shows potential as a biomarker for early HCC diagnosis and