Zhou et al. uncover the pro-tumorigenic role of gut fungus Rhizopus arrhizus in MASLD-HCC. R. arrhizus produces kynurenic acid, which directly binds to tumor cells and activates oncogenic MAPK signaling to promote MASLD-HCC. Zhou et al. also provide therapeutic insights by showing that blocking this host-fungus interaction inhibits MASLD-HCC development.

Zhao et al. show that gut microbial aldehyde-alcohol dehydrogenase (AdhE) degrades metformin, reducing drug exposure and glycemic control in individuals with type 2 diabetes. A clinical trial further demonstrates that the dietary phytochemical daidzein inhibits microbial AdhE and improves metformin efficacy.

Zhang et al. show that lactate regulates necroptosis via RIPK3 lactylation at lysine 63, enhancing kinase activity. This drives tissue injury in ischemia-reperfusion and viral infection, while exercise-induced lactate uses the same mechanism to support muscle remodeling, revealing lactate-promoted necroptosis as key to both pathological and physiological processes.

Zinngrebe et al. propose that adipocyte immunity represents an underappreciated component of host defense, with adipocyte functions extending far beyond energy storage to pathogen sensing and antimicrobial activity. At pathogen entry sites, adipocytes provide local host defense to contain microbial infections and preserve tissue integrity.

Karagiannis and Theodorou et al. show that excess lipids in obesity impair adipose ILC2s via acetyl-CoA carboxylase 1 (ACC1). Deletion of ACC1 disrupts the citrate shuttle and the NAD+/NADH balance, inducing ILC2 loss and adipose tissue hypertrophy. Supplementing with nicotinamide riboside rescues ACC1 deficiency and restores ILC2 and adipose tissue homeostasis.

Yong et al. identify that liver disease is associated with increased osteoarthritis (OA) risk. They uncover a liver-cartilage selenium (Se) axis: hepatic stress impairs selenoprotein P (SELENOP)-mediated Se delivery to cartilage, promoting chondrocyte senescence and joint degeneration. Inorganic Se supplementation restores cartilage selenoprotein expression and mitigates OA in mice, highlighting Se as a nutritionally modifiable factor.

(Cell Metabolism 37, 656–672.e1–e7; March 4, 2025)

Sawada et al. show that reduced hepatic glutamine drives pathogenic CD4+ T cell responses that promote MASLD progression. Restoring liver glutamine suppresses inflammation and limits liver injury. These findings identify T cell glutamine metabolism as a key metabolic checkpoint and promising therapeutic target in MASLD.

Zhang et al. identify SIRT2 as a zonated cholesterol sensor in periportal hepatocytes, where chronic cholesterol overload hyperactivates SIRT2 to suppress CYP7B1‑mediated bile acid synthesis, leading to 27‑hydroxycholesterol accumulation and ultimately driving MASLD‑HCC.

(Cell Metabolism 16, 511–525; October 3, 2012)

Chaib et al. identify PD-L2 as a senescence-associated immune checkpoint that promotes senescent cell persistence during aging; soluble PD-L2 also increases with aging and declines after senolytic treatment in humans. PD-L2 blockade reduces senescent cell burden and improves metabolic and physical function in aged mice.

Women with polyendocrine metabolic ovarian syndrome (PMOS) represent a particularly challenging patient population, characterized by the convergence of reproductive dysfunction, obesity, insulin resistance, and chronic inflammation. The emergence of glucagon-like peptide-1 receptor agonists (GLP-1RAs) offers a transformative therapeutic opportunity, addressing the complex endocrine and reproductive disturbances that underpin this disorder.

Affecting hundreds of millions of women worldwide, polyendocrine metabolic ovarian syndrome (PMOS, formerly polycystic ovary syndrome) carries a significantly higher risk of cardiovascular and metabolic diseases. Here we discuss how renaming this disease reframes a profoundly misunderstood condition for which basic metabolic research remains critically underfunded and fragmented.

(Cell Metabolism 37, 2093–2095; October 7, 2025)

Xiao et al. identify a liver-derived β-hydroxybutyrate-CREM signaling axis that drives CD8+ T cell immunosenescence. Restoring β-hydroxybutyrate reverses T cell exhaustion and improves antitumor, antiviral, and CAR T cell immunity in aged hosts, revealing a metabolic strategy to rejuvenate immune function during aging.

Tang et al. identify host MTDH as a key mediator linking tumor-liver crosstalk to antitumor immunity. Targeting MTDH in hepatocytes and T cells enhances CD8+ T cell function and improves anti-PD-1 therapy, revealing a host-directed strategy to overcome cancer immunosuppression.

Petersen et al. report that 10% weight loss induced by consuming a ketogenic diet causes greater improvements in hepatic metabolic function and intrahepatic triglyceride content than the same weight loss induced by consuming a Mediterranean or very-low-fat plant-forward diet in people with metabolically unhealthy obesity.

Matsuzaki et al. highlight gut microbiota as a critical determinant of how environmental neurotoxicants affect the brain, describing bidirectional interactions between toxicant metabolism, microbial communities, and host responses. These emerging connections provide new perspectives on environmental risk and neurological health.

Vuong and Délépine et al. apply unsupervised clustering to routine neutrophil, lymphocyte, and monocyte counts, thus defining four reproducible and temporally stable immune endotypes of type 2 diabetes. Severe inflammatory diabetes (SIND) displays the greatest inflammatory burden, marked by monocyte-centered immune activation, and is associated with heightened cardiovascular, renal, and mortality risks.

(Cell Metabolism 14, 587–597; November 2, 2011)

(Cell Metabolism 38, 673–693.e1–e17; April 7, 2026)

Protein restriction extends lifespan across species and engages many hallmarks of aging. We propose that these diverse responses can be understood as components of a single coordinated physiological state. This response involves both cellular nutrient sensing and endocrine and neural coordination, with enhanced longevity emerging from this adaptive response.

(Cell Metabolism 23, 206–219; January 12, 2016)

Mereu et al. present ESPACE, a single-cell multi-omic atlas of the human pancreas spanning fetal development, adulthood, and type 2 diabetes. Combining transcriptomics, chromatin accessibility, and spatial imaging, they uncover a rare population of plastic centroacinar cells and hidden diversity among hormone-producing islet cells, informing pancreas regeneration and disease.

In the ongoing discussion as to which beta-adrenergic receptor is transmitting the activating signal in human brown adipose tissue (BAT), Füchtbauer et al. compared a selective beta2-adrenergic agonist to cold exposure, the natural stimulus for brown adipose tissue. Both interventions increased energy expenditure, but only cold substantially activated human BAT.

In this perspective, Hengist et al. introduce a translational bedside-to-outside model, combining highly controlled domiciled feeding with free-living interventions in the same participants, for human nutrition research. This research model aims to overcome issues with translating effect size between experimental settings while acting as a platform for method validation.

Metabolic dysfunction is a defining but poorly understood feature of Alzheimer’s disease. Du et al. show that a brain-penetrant GLP-1 receptor agonist rewires astrocyte-neuron metabolic coupling throu...

Growth differentiation factor 15 (GDF15) suppresses liver inflammation and fibrosis in metabolic dysfunction-associated steatohepatitis (MASH), which is independent of reduced food intake, body weight, or steatosis. The study identifies the hypothalamic-pituitary-adrenal axis as a key mediator, revealing a brain-liver endocrine circuit that protects against liver inflammation independently of weight loss.

The unprecedented broad efficacy of GLP-1 medicines reflects mechanisms beyond weight loss. GLP-1R agonism recruits neural and immune circuits, inter-organ communication, and engages local GLP-1Rs to ...

(Cell Metabolism 38, 1113–1129.e1–e12; June 2, 2026)

(Cell Metabolism 36, 78–89.e1–e5; January 2, 2024)

(Cell Metabolism 37, 2030–2047.e1–e7; October 7, 2025)

(Cell Metabolism 36, 511–525.e1–e7; March 5, 2024)

(Cell Metabolism 25, 86–92; January 10, 2017)

(Cell Metabolism 36, 193–208.e1–e8; January 2, 2024)

(Cell Metabolism 36, 2228–2244.e1–e7; October 1, 2024)

(Cell Metabolism 37, 1–18.e1–e13; May 6, 2025)

(Cell Metabolism 38, 350–369.e1–e8; February 3, 2026)

The mechanisms coordinating the homeostasis of glucose, lactate, fatty acids, and ketones remain unknown. Through quantitative modeling and experiments, Weilandt et al. reveal that these nutrients compete to be oxidized to meet systemic energy demands. Competitive catabolism normally produces homeostasis but, in obesity, converts increased lipolytic propensity into hyperglycemia and hyperinsulinemia.

Liu et al. reveal that maternal vitamin B12 deprivation drives offspring obesity by reducing early-life B. pseudolongum acquisition, and restoring the bacterium or acetate reverses this phenotype via the Ffar2-Ehhadh axis.

(Cell Metabolism 32, 1052–1062.e1–e8; December 1, 2020)

(Cell Metabolism 13, 701–711; June 8, 2011)

Obesity-induced leptin resistance is a major challenge for clinical management and drug development. This study finds that FGF21 synergizes with leptin in counteracting obesity-related metabolic multimorbidity by enhancing leptin sensitivity in hepatocytes via adiponectin-induced expression of leptin receptors.

(Cell Metabolism 35, 84–100.e1–e8; January 3, 2023)

Brown fat controls metabolic health beyond thermogenesis, yet how it communicates with other organs through circulating metabolites remains poorly understood. Wang et al. systematically map brown-fat-associated circulating metabolites and identify a cold-inducible metabolite, 3-hydroxystearic acid, as a brown-fat-derived signal that protects the liver from oxidative stress.

(Cell Metabolism 35, 1915–1930.e1–e8; November 7, 2023)

(Cell Metabolism 36, 1823–1838.e1–e6; August 6, 2024)

Challenging dogmas, Prentki et al. propose an alternative paradigm of obesity-related type 2 diabetes, interpreting insulin resistance, reduced glucose-induced insulin secretion, mild hyperglycemia, and glucosuria not as primary pathological abnormalities but as beneficial allostatic responses to nutrient excess. Therapeutic strategies should focus on glucose fate, not blood glucose levels alone.