Search Results (768)

Breast cancer stem cells (BCSCs) drive tumor progression, metastasis, and therapeutic resistance. Sirtuin 1 (SIRT1) has been implicated in stem cell regulation, but its context-dependent role in BCSC maintenance and the underlying molecular mechanisms remain poorly defined. SIRT1 expression was evaluated in human breast cancer specimens. Pharmacologic and genetic SIRT1 inhibition was assessed in breast cancer cell lines and orthotopic xenograft models to determine effects on stemness, epithelial–mesenchymal transition (EMT), metastasis, and chemoresistance, with emphasis on Wnt/β catenin signaling. SIRT1 was overexpressed in breast cancer and correlated with higher tumor grades. SIRT1 inhibition reduced BCSC markers (CD44, ALDH1), stemness genes (NANOG, SOX-2), mammosphere formation, EMT, and invasion. In vivo, SIRT1 inhibition suppressed tumor growth, blocked lymphatic metastasis, and delayed cisplatin resistance. Mechanistically, these effects were mediated by downregulation of Disheveled 3 (DVL3) and attenuation of Wnt/β catenin signaling. SIRT1 is associated with the maintenance of BCSC-related properties, EMT, and activation of the Wnt/β-catenin pathway in breast cancer. Targeting SIRT1 may represent a potential therapeutic strategy to suppress tumor progression and improve treatment response. Full article

Non-alcoholic fatty liver disease (NAFLD) induces renal injury via the liver–kidney axis, with oxidative stress as the core pathological mechanism. Apigenin (API) and aerobic exercise (AE) exhibit antioxidant and metabolic regulatory properties, but their combined renoprotective effect in NAFLD and the underlying mechanism remain poorly characterized. This study aimed to explore the protective efficacy of API combined with AE against NAFLD-associated renal damage and its association with the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) pathway. A NAFLD mouse model was established via 12-week high-fat-diet feeding, followed by 8-week API intraperitoneal injection and/or treadmill AE intervention. Renal histology, biochemical parameters, inflammatory cytokines, tubular injury markers, and pathway molecules were examined. Combined intervention significantly reduced serum creatinine (SCr) and blood urea nitrogen (BUN), alleviated renal lipid accumulation, and attenuated oxidative stress and inflammation. It significantly downregulated the tubular injury marker KIM-1, and induced a downward trend in NGAL and L-FABP without statistical significance. The combined intervention also enhanced AMPK phosphorylation and upregulated SIRT1 and PGC-1α protein expression, with greater effects than single interventions and significant statistical interactions between the two interventions on these pathway molecules. These results suggest that API combined with AE attenuates NAFLD-related renal injury, and that this protective effect is associated with the upregulation of AMPK phosphorylation and SIRT1/PGC-1α protein expression, the significant statistical interaction between the two interventions suggests the potential involvement of this pathway in mediating renoprotection. These findings provide preliminary evidence for the association between the AMPK/SIRT1/PGC-1α pathway and the renoprotective effect of this combined intervention strategy. Full article

Ageing is driven by chronic inflammation, oxidative stress, and stem cell exhaustion, posing a major global health challenge. Lactic acid bacteria (LAB) fermentation is being investigated as a potential biotechnology to enhance the bioavailability and functionality of natural products, especially polyphenols and bioactive phytochemicals with anti-ageing potential. This review synthesizes recent advances in LAB-fermented natural products and their roles in modulating longevity pathways and stem cell regeneration. LAB fermentation can alter complex plant matrices by releasing or biotransforming substrate-bound phytochemicals and by generating metabolites such as organic acids, peptides, and, in some systems, short-chain fatty acids (SCFAs), cyclic dipeptides (CDPs), or bacterial extracellular vesicles (BEVs); the contribution of each component requires case-specific verification. In cellular and animal models, candidate mechanisms include modulation of nuclear factor kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), and AMP-activated protein kinase–sirtuin 1 (AMPK–SIRT1) signaling, although causal active components are often unresolved. Some LAB-fermented preparations or LAB-derived components have been associated with stem-cell-related outcomes in skin, bone, and neural cell or animal models. CDPs and BEVs are candidate fermentation-associated mediators, but evidence for their independent effects on human ageing remains preliminary. Collectively, LAB-fermented natural products are a promising research area for functional foods and nutraceuticals, but their efficacy and safety for ageing-related outcomes require clinical validation. Future research should focus on standardizing fermentation conditions, identifying active metabolites, and validating their clinical efficacy in human studies. Full article

Cellular senescence is one of the hallmarks of aging. These growth-arrested cells actively secrete inflammatory mediators that reshape the tissue microenvironment and fuel age-related pathology. Sirtuin 1 (SIRT1) is an NAD⁺-dependent deacetylase that regulates senescence largely through its control over mitochondrial integrity and inflammatory signaling. SIRT1 levels and activity fall with age, and this decline directly promotes senescence. SIRT1 maintains mitochondrial function through three interconnected pathways: PGC-1α-driven mitochondria biogenesis, FOXO-dependent antioxidant defense, and mitophagic clearance of damaged organelles. When SIRT1 activity is in an unsteady state, mitochondria become unhealthy. This leads to excessive ROS generation and the leakage of mitochondrial DNA (mtDNA) into the cytosol, which activates the innate immune pathway, consequently resulting in the production of inflammatory cytokines that further inhibit SIRT1. This self-amplifying loop drives cells to irreversible senescence. In this study, we integrate the current understanding of the SIRT1–mitochondria–immune axis within the framework of senescence by examining the biological roles of SIRT1 and the mechanisms that lead to its reduction with aging, while also exploring the interrelated mitochondrial pathways and inflammatory signaling. Furthermore, we assess possible therapeutic strategies targeting this axis and highlight essential questions that necessitate additional research. Full article

Neurodegenerative diseases arise from interacting oxidative, inflammatory, mitochondrial, and proteostatic disturbances. Hydroxytyrosol (HT), an olive phenol, has been proposed as a multitarget neuroprotective compound. This narrative review integrates HT chemistry, parent/metabolite pharmacokinetics, blood–brain barrier (BBB) evidence, mechanisms, disorder-specific models, and human studies. Direct HT evidence is strongest for nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) activation and experimental modulation of α-synuclein; support for AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), mitochondrial protection, nuclear factor-kappa B (NF-κB)-related inflammation, and amyloid-β (Aβ) is predominantly preclinical, whereas tau, autophagic flux, and ubiquitin–proteasome effects remain preliminary. Oral HT is rapidly absorbed but extensively conjugated, and no study has quantified parent HT or its major metabolites in the human brain or cerebrospinal fluid after oral supplementation. Isolated-HT trials show systemic antioxidant or anti-inflammatory biomarker effects, while cognitive findings derive mainly from phenolic-rich olive matrices and cannot be assigned to HT alone. No disease-modifying efficacy has been established for isolated HT in Alzheimer’s disease (AD), Parkinson’s disease (PD), or related disorders. HT is therefore a mechanistically plausible candidate, but human brain exposure, dose–response, and efficacy require adequately powered disease-specific trials. Full article

Barth syndrome (BTHS) is a rare, X-linked genetic disorder caused by mutations in the enzyme TAFAZZIN (TAZ), resulting in insufficient cardiolipin (CL) remodeling and mitochondrial dysfunction. While BTHS respiratory distress and breathing difficulties are commonly reported, the precise role of intrinsic respiratory tissue vulnerabilities has only recently begun to be appreciated. Historically, BTHS respiratory distress is frequently attributed to secondary consequences like cardiomyopathy or generalized skeletal myopathy, leaving the intrinsic vulnerability of vital respiratory muscles poorly understood. Using a patient-tailored point mutant knock-in mouse model (Taz^PM) harboring a stable but enzymatically deficient Taz^D75H protein, we investigated the autonomous physiological and metabolic responses in the diaphragm and lungs. Contrary to the paradigm that respiratory muscles are unaffected, Taz^PM diaphragms exhibit structurally abnormal mitochondria and undergo a survival-critical, bifurcated compensatory remodeling response to prevent fatal respiratory failure under severe bioenergetic stress. The Taz^PM adaptive mechanism is orchestrated by chronic activation of the mitochondrial Integrated Stress Response (ISR) via the Gcn2/eIF2α signaling pathway. This stress pathway halts global translation to conserve cellular ATP at the expense of reduced NAD+ levels, while selectively upregulating defensive mitokines and metabolic sirtuins and structural muscle remodeling. Furthermore, the Taz^PM diaphragm transitions into a highly specialized, slow-twitch motor system that is expected to reduce the energy cost per contraction. Concurrently, despite Taz^PM lungs exhibiting structurally abnormal mitochondria, they resist generalized mitochondrial collapse despite ADP reduction, executing tissue-specific metabolic reprogramming and localized biochemical adaptations to sustain respiratory homeostasis. Full article

The field of cosmetic science is rapidly evolving due to advances in skin biology research and increasing demand for evidence-based, personalized skincare solutions. A key aspect of this progress is the targeted modulation of biological macromolecules involved in skin aging, pigmentation, inflammation, and tissue regeneration. This review highlights major molecular targets in modern cosmetic research, focusing on telomerase, histone deacetylases (particularly sirtuins), matrix metalloproteinases, antioxidant enzymes, CD44 receptor, tyrosinase, microphthalmia-associated transcription factor, and melanocortin receptors, all of which regulate processes such as DNA repair, gene expression, extracellular matrix remodeling, and melanogenesis. Recent findings indicate that natural and synthetic compounds can effectively modulate these targets, supporting anti-aging and depigmenting strategies. Telomerase activators and sirtuin modulators show potential in maintaining cellular homeostasis and delaying skin aging. In pigmentation research, the transition from mushroom to human tyrosinase assays has enabled development of more selective inhibitors, including thiamidol. The review also addresses molecular targets relevant to inflammatory skin disorders, scars, and skin atrophy. Advances in molecular and biotechnological methods are expected to improve mechanistic understanding and support the rational design of safer, more effective next-generation cosmetic ingredients and formulations. Full article

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder strongly associated with mitochondrial dysfunction and impaired proteostasis. Mutations in TARDBP, encoding TAR DNA-binding protein 43 (TDP-43), contribute to disease pathogenesis through cytoplasmic mislocalization and aggregation. Among these, the ALS-linked TDP-43^G376D mutation has been previously associated with oxidative stress, mitochondrial fragmentation, and impaired oxidative phosphorylation. Here, we investigated the impact of TDP-43^G376D on Mitochondrial Quality Control (MQC) pathways using patient-derived dermal fibroblasts carrying the mutation at early and advanced disease stages, complemented by HEK293T and Neuro2a cellular models expressing mutant TDP-43. We show that TDP-43^G376D impairs mitophagic flux, as evidenced by reduced delivery of damaged mitochondria to lysosomes. This was accompanied by pronounced disruption of mitochondrial cristae architecture and accumulation of mitochondrial DNA damage, indicating compromised mitochondrial genome integrity. Furthermore, TDP-43^G376D induces sustained activation of the mitochondrial Unfolded Protein Response (UPR^mt), consistent with persistent mitochondrial stress, while selectively impairing the sirtuin-dependent antioxidant branch. In parallel, activation of the Endoplasmic Reticulum UPR (UPR^ER) was observed, indicating a coordinated engagement of cellular stress pathways. Collectively, our findings identify coordinated alterations in multiple MQC pathways associated with TDP-43^G376D rather than isolated mitochondrial defects, supporting further investigation of these pathways in larger and disease-relevant ALS models. Full article

Background: Large yellow tea (LYT), a distinctive variety made from mature leaves, has recently gained attention for its remarkable health benefits. However, whether these benefits can be transmitted from mother to offspring remains unexplored. Purpose: This study investigated whether maternal LYT consumption confers intergenerational protection against metabolic and behavioral disorders induced by perinatal bisphenol A (BPA) exposure in F1 offspring. Methods: A mouse model of perinatal BPA exposure (0.03% in diet) was established with or without maternal LYT supplementation (2.5% in diet). Metabolic parameters were assessed through biochemical assays and gene expression analysis (RT-PCR). Energy expenditure and spontaneous activity were monitored using a Comprehensive Lab Animal Monitoring System (CLAMS). Hippocampal proteomic profiling was performed using label-free quantitative proteomics. Results: LYT significantly reduced maternal BPA body burden, potentially via limiting absorption, enhancing glucuronidation metabolism, and promoting excretion. Notably, LYT exhibited bidirectional metabolic regulation, alleviating gestational hyperglycemia in dams while restoring hypoglycemia in offspring, and normalizing underweight and hypolipidemia. Mechanistically, the SIRT6 (sirtuin 6)/FOXO1 and SIRT6/SREBP1 pathways may be involved in regulating gluconeogenesis and lipogenesis. Concurrently, LYT rectified BPA-induced hyperactivity and reduced excessive energy expenditure. Proteomic analysis revealed that LYT partially restores BPA-induced dysregulation of cholesterol metabolism and glutamatergic/GABAergic synaptic pathways, which may contribute to rebalancing synaptic homeostasis. Conclusions: These findings suggest that maternal LYT supplementation confers intergenerational protection against BPA-induced metabolic and behavioral disorders in mice, potentially acting through enhanced toxin clearance, bidirectional metabolic regulation, behavioral normalization, and partial restoration of hippocampal synaptic homeostasis. This study provides a theoretical basis for developing natural dietary interventions to mitigate developmental toxicant-induced health risks. Full article

Glaucoma is the leading cause of irreversible blindness worldwide and a paradigmatic age-related neurodegenerative disease in which retinal ganglion cells (RGCs) are selectively lost through mechanisms that extend beyond intraocular pressure. Age-dependent NAD⁺ depletion in RGCs, compounded by the progressive impairment of NAD⁺ biosynthesis and by the hyperactivation of NAD⁺-consuming enzymes under oxidative stress, defines a metabolic vulnerability that current pressure-lowering therapy does not address. Pyrroloquinoline quinone (PQQ) is a tricyclic ortho-quinone present in plant-derived foods that acts on the NAD⁺ pool through a mechanism distinct from that of conventional precursors. Rather than expanding the pool by net synthesis, PQQ binds lactate dehydrogenase and oxidizes NADH to NAD⁺ through catalytic redox cycling, raising NAD⁺ availability without altering the total dinucleotide content and independently of the two biosynthetic enzymes selectively impaired in glaucomatous RGCs. The resulting increase in NAD⁺ availability activates sirtuin-dependent programs that drive mitochondrial biogenesis. PQQ additionally engages an NRF2-dependent antioxidant response, addressing molecular deficits directly implicated in glaucomatous RGC degeneration. In retinal cell models, PQQ preserves ATP content and viability under mitochondrial stress. In vivo, it protects RGC density in optic nerve degeneration models and elevates NAD⁺ along the visual pathway. A randomized clinical trial demonstrated functional improvement in glaucoma patients receiving a PQQ-containing combination. The redox biochemistry of PQQ places it at a mechanistic intersection with the NAD⁺ deficit that characterizes glaucomatous neurodegeneration. Its complementarity with conventional NAD⁺ precursors and neuroprotective compounds acting on distinct molecular targets supports the design of combination regimens addressing multiple dimensions of RGC vulnerability. Critical questions regarding bioavailability, molecular target characterization, and clinical validation in dedicated trials remain open. Full article

Background/Objectives: Alzheimer’s disease (AD) is associated with amyloid-β (Aβ)-induced neuronal injury, oxidative stress, inflammatory activation, and cellular senescence. Phycocyanobilin (PCB), an algae nutritive compound, has shown neuroprotective potential, but whether it attenuates Aβ-induced neuronal senescence remains unclear. This study investigated the protective effects of PCB against Aβ_1–42 oligomer-induced senescence-like alterations in SH-SY5Y cells and examined the involvement of sirtuin 1 (SIRT1) signaling. Methods: Differentiated SH-SY5Y cells were pretreated with PCB (50 μmol/L) in the presence or absence of EX527 (10 μmol/L) for 24 h, followed by exposure to Aβ_1–42 oligomers (20 μmol/L) for an additional 24 h. Cell viability, lactate dehydrogenase (LDH) release, senescence-associated β-galactosidase (SA-β-gal) staining, senescence-associated heterochromatin foci (SAHF)-associated di-/tri-methylated histone H3 lysine 9 (H3K9me2/3) fluorescence, senescence-associated secretory phenotype (SASP)-related cytokines, phosphorylated histone H2AX (γ-H2AX) accumulation, Ki67 expression, p53/p21/p16 signaling, and silent information regulator 1 (SIRT1) expression and activity were assessed using cell counting kit-8 assay, LDH assay, enzyme-linked immunosorbent assay, immunofluorescence staining, quantitative real-time PCR analysis, Western blotting, and fluorometric enzymatic activity assay. Results: Aβ_1–42 oligomers reduced cell viability, increased LDH release, promoted SA-β-gal positivity, enhanced H3K9me2/3 and γ-H2AX signals, elevated IL-1β, IL-6, and IL-8 levels, suppressed Ki67 expression, and upregulated p53, p21, and p16. PCB pretreatment markedly attenuated these cytotoxic, senescence-associated inflammatory, and DNA damage-related responses while restoring SIRT1 mRNA, protein expression, and enzymatic activity. EX527 partially reversed these protective effects. Conclusions: PCB attenuates Aβ_1–42 oligomer-induced neuronal senescence-like alterations, at least partly through SIRT1-associated regulation, supporting its potential as a naturally derived anti-senescent neuroprotective compound for AD-related neuronal aging. Full article

This review examines the structural variety, distribution, and physicochemical properties of chlorogenic acids (CGAs), identifying coffee and green coffee as the leading dietary sources of these compounds. Preclinical studies indicate that plant-derived phenolic compounds exhibit strong antioxidant, anti-inflammatory, neuroprotective, cardioprotective, and antidiabetic effects across various disease models. The biological effectiveness of CGAs is attributed to their modulation of cellular signaling pathways, particularly by activating the erythroid 2-related factor 2 antioxidant defense mechanism and inhibiting the pro-inflammatory nuclear factor kappa B pathway. The regulation of the energy-sensing Sirtuin 1 and AMP-activated protein kinase pathways further enhances these therapeutic effects. In the gastrointestinal tract, CGAs serve as key modulators of the microbiota–gut–brain axis by exerting prebiotic-like effects, lowering the Firmicutes/Bacteroidetes ratio, promoting the production of short-chain fatty acids, and preserving gut barrier integrity. Some preclinical studies with coffee, Ilex paraguariensis, Eugenia uniflora, and other CGAs-rich extracts are also discussed. However, despite strong preclinical evidence, translating these findings into human clinical settings remains inconsistent due to significant individual differences in gut microbiota metabolism and the confounding effects of other components in dietary supplements, such as caffeine. Considering this, the review will first explore the molecular mechanisms supporting the potential development of CGAs as preventive interventions, while also discussing current human trials demonstrating selective improvements in neurological, cardiovascular, and metabolic functions. It will also highlight a historical limitation: the lack of studies on the bioavailability, bioactivity, and efficacy of isolated CGAs. The review will conclude by addressing the constraints of clinical studies, emphasizing the urgent need for future precision nutrition frameworks that employ standardized CGAs formulations to enhance potential therapeutic outcomes. Full article

Identifying physiological changes during the transition period is essential for improving the health and productivity of dairy goats. This study evaluated hematological, biochemical, hormonal, oxidative stress, and molecular alterations in Shami goats during the pre-pregnancy, late pregnancy, and early lactation periods. Eighty clinically healthy goats were examined, and blood samples were analyzed for hematological indices, metabolic and hormonal profiles, oxidative stress biomarkers, and relative expression of genes associated with energy metabolism, antioxidant defense, inflammation, and autophagy. Late pregnancy was characterized by significant (p < 0.05) increases in red blood cell count (RBCs), hemoglobin concentration (Hb), neutrophils, albumin, globulin, urea, insulin-like growth factor-1 (IGF-I), and malondialdehyde (MDA), accompanied by decreased glucose, cholesterol, total protein (TP), antioxidant markers, total leukocyte count, packed cell volume, and monocytes. Early lactation was associated with higher non-esterified fatty acid, triiodothyronine (T3), and thyroxine (T4) levels. Genes involved in lipid mobilization and oxidation, ketogenesis, inflammation, cellular stress, and autophagy; sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor alpha (PPARA), carnitine palmitoyltransferase 1a (CPT1A), 3-hydroxy-3-methylglutaryl-coenzyme a synthase 2 (HMGCS2), cluster of differentiation 36 (CD36), lipase E (LIPE), protein kinase amp-activated catalytic subunit alpha 1 (PRKAA1), solute carrier family 2 member 1 (SLC2A1), haptoglobin (HP), interleukin 6 (IL6), heat shock protein 70 (HSP70), heme oxygenase 1 (HMOX1), beclin 1 (BECN1), and autophagy-related protein 5 (ATG5) were significantly upregulated, whereas antioxidant- and glucose transport-related genes nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 1 (GPX1), catalase (CAT), thioredoxin (TXN), and solute carrier family 2 member 4 (SLC2A4) were downregulated during the transition period. The results indicate well-orchestrated metabolic and molecular adaptations that can be employed as biological indicators to track the physiological status of Shami goats. These findings fulfilled the study objective and identified potential biomarkers of the transition period in Shami goats. Full article

Aging is characterized by a progressive decline in physiological resilience and increased susceptibility to chronic diseases, including neurodegenerative disorders. Emerging evidence indicates that low-dose stressors (collectively termed hormetic stimuli) activate adaptive cellular responses that enhance stress resistance, promote repair mechanisms, and ultimately extend healthspan. This narrative review synthesizes current knowledge on hormesis in the context of aging, with a focus on key molecular pathways including nuclear factor erythroid 2-related factor 2 (Nrf2), sirtuins, autophagy, and mitohormesis. We examine how lifestyle interventions (physical exercise, caloric restriction, mild thermal stress) and emerging pharmacological agents induce beneficial adaptive responses, while critically evaluating their translational potential in clinical and public health settings. Special emphasis is placed on the role of hormesis in counteracting neurodegeneration, the utility of autophagy and systemic aging biomarkers (epigenetic clocks, inflammaging scores) for precision dosing, and the limitations imposed by inter-individual variability, age-related decline in adaptive capacity, and risks of overexposure. Importantly, this review distinguishes experimentally demonstrated hormetic responses from broader adaptive stress responses and critically evaluates situations in which hormetic mechanisms may be insufficient, maladaptive, or clinically inappropriate. Understanding the delicate balance between beneficial and detrimental stress responses is essential for leveraging hormesis as a robust strategy to counteract aging and age-related diseases. We further propose a multilevel framework integrating molecular mechanisms with clinical outcomes, positioning hormesis as a key determinant of adaptive resilience (stress resistance, mitochondrial function, HRV, VO₂max) in aging. Full article

Background/Objectives: As obesity continues to increase globally, it has become a major contributor to the growing burden of metabolic diseases, including type 2 diabetes mellitus, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD). Hepatic lipid accumulation during obesity contributes to oxidative stress and alterations in mitochondrial homeostasis, key features of NAFLD progression. This study investigated whether vitamin D insufficiency aggravates obesity-related hepatic steatosis in association with changes in hepatic sirtuin 1 (SIRT1) activity and nuclear factor erythroid 2–related factor 2 (Nrf2)-related antioxidant gene expression. Methods: Male C57BL/6J mice were maintained on one of three dietary regimens for 16 weeks: a normal diet (NOR; 10% fat containing 1000 IU vitamin D/kg), a high-fat diet (HF; 60% fat containing 1000 IU vitamin D/kg), or a vitamin D-deficient high-fat diet (HF + NVD; 60% fat with no added vitamin D). Results: Vitamin D insufficiency in HF-fed mice (HF + NVD) was associated with significantly higher hepatic triglyceride accumulation and lipid peroxidation than those observed in the HF group. A concomitant reduction in the expression of Nrf2-dependent antioxidant genes was observed in the HF + NVD group. Furthermore, hepatic mitochondrial DNA content as well as hepatic SIRT1 mRNA level and activity, the NAD⁺/NADH ratio, and CPT1α mRNA expression were significantly decreased in the HF + NVD group. Conclusions: An inadequate vitamin D status was associated with greater hepatic lipid deposition, enhanced oxidative stress, and reduced hepatic SIRT1 activity, and lower expression of Nrf2-related antioxidant genes. These findings support that maintaining adequate vitamin D status might help preserve hepatic metabolic homeostasis during obesity. Full article