Addressing endocrine resistance in hormone receptor-positive breast cancer, Padrão et al. identify the glucocorticoid receptor (GR) as the key transducer of fasting benefits. They demonstrate that pharmacological GR acti...Addressing endocrine resistance in hormone receptor-positive breast cancer, Padrão et al. identify the glucocorticoid receptor (GR) as the key transducer of fasting benefits. They demonstrate that pharmacological GR activation recapitulates antitumor efficacy, offering a targeted therapeutic avenue that avoids the challenges of rigorous dieting.
Trends Endocrinol Metab
· 2026 Mar · PMID 41820089
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Trimethylamine-N-oxide (TMAO), a gut microbial metabolite derived from dietary choline and carnitine, has emerged as a pivotal link between diet, microbial metabolism, and host immunity. Beyond its historical role as a m...Trimethylamine-N-oxide (TMAO), a gut microbial metabolite derived from dietary choline and carnitine, has emerged as a pivotal link between diet, microbial metabolism, and host immunity. Beyond its historical role as a marine osmolyte, TMAO engages core immune pathways-driving oxidative stress, inflammasome activation, and type I interferon signaling-to shape macrophage polarization, T cell responses, and systemic immune tone. These actions place TMAO at the intersection of chronic diseases, exacerbating cardiovascular, metabolic, renal, and neurodegenerative pathology while paradoxically enhancing antitumor immunity in pancreatic and breast cancers. Such duality underscores its significance as both a biomarker and a therapeutic target. We discuss current advances in TMAO biology, immune mechanisms, and strategies to modulate its activity through diet, microbiome interventions, and enzymatic inhibition.
Continuous glucose monitoring (CGM) has become standard care in type 1 diabetes, yet the key measures used to interpret CGM data, such as time spent within, below, or above the target glucose range, and glycemic variabil...Continuous glucose monitoring (CGM) has become standard care in type 1 diabetes, yet the key measures used to interpret CGM data, such as time spent within, below, or above the target glucose range, and glycemic variability, remain based on outdated thresholds. We discuss why updating these targets is essential for modern diabetes care.
Heme availability shapes mitochondrial function, redox balance, and innate immune signaling. Recent studies reveal threshold-dependent heme states that predispose cells to cuproptosis, ferroptosis, apoptosis, pyroptosis,...Heme availability shapes mitochondrial function, redox balance, and innate immune signaling. Recent studies reveal threshold-dependent heme states that predispose cells to cuproptosis, ferroptosis, apoptosis, pyroptosis, or PANoptosis. Viewing heme as a metabolic rheostat provides a unifying framework for interpreting regulated cell death across cancer, infection, and metabolic disease.
Trends Endocrinol Metab
· 2026 Mar · PMID 41813553
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Cellular senescence is a complex cell fate characterized by stable cell cycle arrest and other heterogeneous changes. Senescent cells play a causal role in aging, although the underlying mechanisms remain under active in...Cellular senescence is a complex cell fate characterized by stable cell cycle arrest and other heterogeneous changes. Senescent cells play a causal role in aging, although the underlying mechanisms remain under active investigation. In this opinion article, we propose that senescent cells can act as key mediators of interorgan communication of aging. Recent work defines multifaceted mechanisms, including the production of senescence-associated secretory phenotype factors that act to propagate senescence signals to nearby and distant cells, as well as age-related alterations in immune function that drive chronic inflammation, known as 'inflammaging'. Further investigation of these mechanisms could yield improved strategies to target senescent cells and mitigate their effects on systemic aging via interorgan communication of aging.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by liver disease progression and cardiovascular disease (CVD). The mechanism linking MASLD with CVD is not fully understood. Here, we repo...Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by liver disease progression and cardiovascular disease (CVD). The mechanism linking MASLD with CVD is not fully understood. Here, we report experimental and clinical studies suggesting that platelet activation may be implicated in the pathogenesis of MASLD and CVD.
Mitochondria play a central role in energy metabolism, redox balance, and cellular homeostasis, and their dysfunction has been implicated in the pathogenesis of complex human diseases. Advances in systems biology and omi...Mitochondria play a central role in energy metabolism, redox balance, and cellular homeostasis, and their dysfunction has been implicated in the pathogenesis of complex human diseases. Advances in systems biology and omics technologies have elucidated the mechanisms underlying these conditions, including metabolic dysfunction, mitochondrial impairment, inflammation, and redox imbalance. Preclinical and early clinical studies of combined metabolic activators (CMA), a formulation of bioactive metabolites, have demonstrated improvements in mitochondrial function and systemic metabolic profiles across multiple diseases. In this review, we provide a comprehensive overview of the mechanistic rationale for CMA, summarize evidence from preclinical models and clinical studies investigating CMA and its components, and evaluate its translational potential and challenges as a mitochondrial-targeted therapeutic strategy for complex human diseases.
The ovary is more than just a reproductive organ. Recent evidence in mammalian and invertebrate models consistently highlights novel mechanistic insights into organ-ovary crosstalk via classical hormones and emerging sec...The ovary is more than just a reproductive organ. Recent evidence in mammalian and invertebrate models consistently highlights novel mechanistic insights into organ-ovary crosstalk via classical hormones and emerging secretomes, such as extracellular vesicles. Thus, the ovary functions as an integral organ to maintain organismal health through crosstalk with various organs.
Vasculature and surrounding adipose tissue constitute a dynamic interface, maintaining cardiometabolic homeostasis. Obesity rewires this crosstalk into a self-perpetuating cycle. Two recent studies by Suda et al. and Hof...Vasculature and surrounding adipose tissue constitute a dynamic interface, maintaining cardiometabolic homeostasis. Obesity rewires this crosstalk into a self-perpetuating cycle. Two recent studies by Suda et al. and Hof et al., respectively, established the 'endothelium-to-adipose' and 'adipose-to-endothelium' arms, linking endothelial and adipose pathology and motivating multimechanism therapies for cardiometabolic diseases.
Mitochondria act as key metabolic regulators beyond ATP production, and the understanding of how cellular signaling modifies mitochondrial gene expression is currently being explored. Recent evidence links kinases such a...Mitochondria act as key metabolic regulators beyond ATP production, and the understanding of how cellular signaling modifies mitochondrial gene expression is currently being explored. Recent evidence links kinases such as mitogen-activated protein kinase-interacting kinases, hexokinase 1, and eukaryotic elongation factor 2 kinase to mitochondrial function, influencing metabolic adaptation, inflammation, and survival under nutrient stress, with implications for obesity and aging.
Microbes can extensively regulate the physiological or pathological processes of host organs by secreting metabolites. Recently, Zhang et al. demonstrated that ectopic Catenibacterium mitsuokai could secrete quinolinic a...Microbes can extensively regulate the physiological or pathological processes of host organs by secreting metabolites. Recently, Zhang et al. demonstrated that ectopic Catenibacterium mitsuokai could secrete quinolinic acid, activating the TIE2/PI3K/AKT pathway to drive hepatocellular carcinoma. These findings offer new insights into the microbial metabolite-target organ axis.
The metabolite substrates of numerous transporters remain largely elusive. Two recent studies by Khan et al. and Dias et al. identify SLC25A45 as a mitochondrial transporter of methylated amino acids that supports de nov...The metabolite substrates of numerous transporters remain largely elusive. Two recent studies by Khan et al. and Dias et al. identify SLC25A45 as a mitochondrial transporter of methylated amino acids that supports de novo carnitine synthesis, providing a valuable strategy for deorphanizing transporters and novel insights into cytoplasm-mitochondria communication and metabolic coordination.
Skin vascular aging is characterized by a specific loss of capillary-associated macrophages (CAMs), driven by impaired local proliferation. This depletion causes microvascular dysfunction. Restoring CAMs via colony-stimu...Skin vascular aging is characterized by a specific loss of capillary-associated macrophages (CAMs), driven by impaired local proliferation. This depletion causes microvascular dysfunction. Restoring CAMs via colony-stimulating factor 1 stimulation improves capillary flow, identifying a promising therapeutic target for aging-related and diabetic vascular complications.
Through metabolic remodeling, tumor cells can modulate neighboring CD8 T cell function via metabolites. A recent study by Ma et al., published in Immunity, reveals that tumor-cell-derived succinate exhibits an antitumor...Through metabolic remodeling, tumor cells can modulate neighboring CD8 T cell function via metabolites. A recent study by Ma et al., published in Immunity, reveals that tumor-cell-derived succinate exhibits an antitumor immune effect, promoting the survival and stemness of CD8 T cells by enhancing mitochondrial fitness and inducing epigenetic reprogramming.
Emerging evidence suggests an interplay between the molecular clock and mitochondrial dynamics in skeletal muscle. In this Forum article, we hypothesize that exercise, as a metabolic challenge, provides a powerful physio...Emerging evidence suggests an interplay between the molecular clock and mitochondrial dynamics in skeletal muscle. In this Forum article, we hypothesize that exercise, as a metabolic challenge, provides a powerful physiological model to investigate the clock-mitochondria axis and its regulatory role in muscle function and metabolic health in humans.
Since the discovery that individuals with active brown adipose tissue (BAT) have lower prevalence of cardiometabolic diseases, it has been hypothesized that this depot can be targeted to improve human metabolic health. A...Since the discovery that individuals with active brown adipose tissue (BAT) have lower prevalence of cardiometabolic diseases, it has been hypothesized that this depot can be targeted to improve human metabolic health. A major limitation with BAT, however, is that it is silenced under physiological temperatures, and the mechanisms that restrict its activation are not completely elucidated. To unlock the true potential of BAT, it is critical to understand the mechanisms governing its silencing. Herein, we provide an integrated review of the main regulatory factors that suppress thermogenic adipocytes, which we have termed 'thermogenic silencers', and present a series of perspectives to position thermogenic silencers as novel targets for the improvement of metabolic health in humans.
Once controversial, paternal non-genetic inheritance is becoming widely accepted. In a recent study, Yin et al. expand this burgeoning field by demonstrating that the benefits of paternal exercise are passed to progeny v...Once controversial, paternal non-genetic inheritance is becoming widely accepted. In a recent study, Yin et al. expand this burgeoning field by demonstrating that the benefits of paternal exercise are passed to progeny via modulating sperm miRNAs. These sperm miRNAs regulate the corepressor NCor1 during embryogenesis to casually transmit improved fitness and metabolism to offspring.
Intramuscular adipose tissue (IMAT) is associated with impaired muscle regeneration, but whether it directly hinders recovery remains unclear. Norris and colleagues show that preventing IMAT formation after injury promot...Intramuscular adipose tissue (IMAT) is associated with impaired muscle regeneration, but whether it directly hinders recovery remains unclear. Norris and colleagues show that preventing IMAT formation after injury promotes new myofiber formation and growth, likely by physically restricting the space required for effective muscle regeneration.