Search Results (2,494)

A comprehensive assessment of allograft quality is essential for predicting successful transplantation and graft survival. Elevated levels of flavin mononucleotide (FMN) in perfusate obtained during hypothermic oxygenated perfusion (HOPE) may serve as a promising predictor of early graft dysfunction and post-transplant complications. The aim of this study was to evaluate the feasibility of applying an FMN determination method to HTK-based perfusion solutions used during liver machine perfusion. The spectrofluorimetric method for FMN determination in modified HTK perfusion solution (modHTK) was evaluated for the following parameters: linearity, accuracy, repeatability, reproducibility, and stability. The study demonstrated the suitability of the quantitative FMN determination method for modHTK solution used during HOPE of liver grafts. Full article

Organoids are three-dimensional, stem-cell-derived tissue constructs that recapitulate the architecture and function of native organs, and they have rapidly emerged as transformative tools in regenerative medicine. Their translation from laboratory models to clinical therapies remains constrained, however, by the limitations of conventional culture matrices. Matrigel is the most widely used matrix. It suffers from batch-to-batch variability, an undefined composition, poor mechanical tunability, and a lack of instructive bioactivity. Bioactive ceramics offer a compelling alternative. Encompassing silicate-, phosphate-, and oxide-based formulations, these materials provide controllable ion-release profiles and structural versatility. They also possess a proven capacity to modulate cell behavior through biochemical and biophysical cues. This review systematically examines how the defining properties of bioactive ceramics intersect with the requirements of organoid formation, maturation, and transplantation. We focus on four key properties: ion release, surface bioactivity, mechanical support, and immunomodulation. We survey established and emerging combinations across bone, liver, intestine, biliary, and thyroid organoid systems. Fabrication strategies, including 3D-printed and sol–gel-derived ceramic scaffolds, are also discussed. Finally, we critically assess remaining challenges in vascularization, immune compatibility, and clinical scale-up, and we propose that the deliberate co-design of bioactive ceramics and organoid biology represents a paradigm shift in regenerative medicine. This approach offers a path toward functional, transplantable tissue constructs with genuine therapeutic potential. Full article

Background/Objectives: In cirrhotic patients, guidelines generally recommend maintaining mean arterial pressure (MAP) ≥ 65 mmHg, but the prognostic impact of MAP in transplant candidates is unclear. This study aimed to evaluate the association between MAP and waitlist mortality and cirrhosis-related complications in patients listed for liver transplantation. Methods: We conducted a retrospective cohort study of 103 adults (age ≥ 18 years) with cirrhosis listed for liver transplantation (MELD 20–24) at a single center (2019–2023). Patients with hepatocellular carcinoma were excluded. The primary outcome was death on the transplant waitlist (n = 9 events). Logistic regression was used to assess the association of MAP (per 1 mmHg) with mortality. Continuous variables were compared using the t-test, and categorical variables were compared using the chi-square test; p < 0.05 was considered significant. Results: Mean MAP at listing was significantly higher in survivors than non-survivors (83.2 ± 9.4 vs. 76.9 ± 8.7 mmHg; p = 0.04). In logistic regression, higher MAP was associated with lower odds of waitlist death (unadjusted odds ratio [OR] per 1 mmHg increase = 0.94; 95% confidence interval [CI] 0.89–0.99; p = 0.041). Subgroup analysis showed a significant inverse association between MAP and hepatorenal syndrome (HRS) (OR per 1 mmHg = 0.94; 95% CI 0.89–0.98; p = 0.011), whereas MAP was not significantly associated with hepatic encephalopathy, ascites, or variceal bleeding (all p > 0.2). Conclusions: Among the cirrhotic patients listed for transplantation, lower MAP at baseline is associated with waitlist mortality and hepatorenal syndrome. These findings should be interpreted cautiously given the small number of events and require validation in larger cohorts. Full article

Background: Kasai hepatoportoenterostomy (KPE) remains first-line therapy for biliary atresia(BA), yet the majority of patients will ultimately require liver transplantation. In centres where both KPE and paediatric liver transplantation are performed, KPE has been understood since the early 2000s as the first stage of a two-stage strategy, and the individual technical elements described here are established practice. What is reported is their uniform application as a single written protocol from the first case of the series, together with native liver and transplant outcomes in the resulting cohort. The technical conduct of KPE directly influences the safety and complexity of subsequent transplantation, yet operative decisions at the time of KPE have rarely been evaluated from a transplant-optimisation perspective. We describe a standardised KPE approach incorporating three technical modifications intended to preserve favourable conditions for eventual hepatic replacement and report native liver and transplant outcomes in the resulting cohort. Methods: A retrospective analysis was conducted of 74 consecutive KPE procedures performed by a single surgeon between 2014 and 2025 at Schneider Children’s Medical Center, Israel. The operative approach incorporated three deliberate modifications applied uniformly from the first case: a transverse subcostal incision aligned with future transplant access, avoidance of liver mobilisation and exteriorisation, and standardisation of the Roux limb at 50 cm. Primary outcomes were native liver survival and transplant operative parameters. Results: Of the 74 patients, 39 (52.7%) maintained their native liver throughout follow-up, while 35 (47.3%) required liver transplantation. No peri-operative mortality occurred. Median age at KPE was 53 days. In the Cox model, post-KPE portal hypertension (adjusted hazard ratio (aHR) 3.63, 95% confidence interval (CI) 1.40–9.42, p = 0.008) and hepatopulmonary syndrome (adjusted HR 10.23, 95% CI 2.19–47.85, p = 0.003) were associated with eventual transplantation; complications were modelled as fixed (ever/never) covariates because onset dates were not consistently retrievable, and these estimates may be subject to immortal-time bias. Among transplanted patients, the median operative time was 8.0 h (interquartile range (IQR) 6.0–10.2) (n = 34); intraoperative blood loss was documented in 15 of 35 patients (median 300 mL (IQR 205–450)). Conclusions: A standardised, transplant-orientated KPE approach was applied uniformly across 74 consecutive cases; 52.7% maintained their native liver, and transplantation in the remainder proceeded without peri-operative mortality. This series was descriptive by design and included no comparator group that operated without these modifications; it therefore cannot establish whether the modifications influence the complexity of subsequent transplantation, and no such inference should be drawn. Post-KPE portal hypertension and hepatopulmonary syndrome are markers associated with transplant requirement and should prompt intensified surveillance. The approach represents the standardisation of existing practice rather than a new technique. Full article

Background/Objectives: Cardiac comorbidities are increasingly common among liver transplant candidates, particularly those with metabolic dysfunction-associated steatohepatitis (MASH)-related cirrhosis. Although the Liver Transplant Comorbidity Index identifies coronary artery disease (CAD) as a predictor of post-transplant mortality, the impact of overall cardiac comorbidity burden on early outcomes after liver transplantation remains unclear. We evaluated the association between pre-transplant cardiac comorbidities and early post-transplant outcomes, with emphasis on MASH-related cirrhosis. Methods: We performed a retrospective cohort study using the TriNetX US Collaborative Research Network. Adults undergoing first-time isolated liver transplantation through May 2026 were included. Pre-transplant CAD, heart failure (HF), and atrial fibrillation (AF) documented within 12 months before transplantation were identified using ICD-10-CM codes. Patients were categorized by cardiac comorbidity burden (0–3 conditions). Recipients with any cardiac comorbidity underwent 1:1 propensity score matching to those without cardiac disease using 16 baseline demographic, clinical, and laboratory variables, including MELD-Na. The estimand was the average treatment effect in the treated patients. Primary outcomes comprised 30- and 90-day all-cause mortality. Secondary outcomes included a prespecified restricted major adverse cardiac event (MACE) composite, limited to hard endpoints (death, myocardial infarction, cardiac arrest, ischemic stroke), and a broader composite, i.e., acute kidney injury, prolonged mechanical ventilation, vasopressor requirement, renal replacement therapy, ICU and hospital length of stay, and 90-day readmission. Results: Among 5124 recipients, 986 (19.2%) exhibited at least one cardiac comorbidity. After matching, 974 patients remained in each group. Pre-transplant cardiac comorbidity was associated with higher 30- and 90-day mortality and increased risks of all secondary outcomes. The association with MACE persisted but was attenuated when restricted to hard endpoints (90-day RR 1.55; 95% CI 1.19–2.03) when compared with the broad composite (RR 1.75; 95% CI 1.40–2.18). MASH recipients with cardiac comorbidities experienced numerically higher event rates than did non-MASH recipients, but interaction estimates were imprecise and non-significant. In separate matched analyses, AF was most strongly associated with MACE, whereas CAD showed the strongest association with mortality. Conclusions: Pre-transplant cardiac comorbidity burden is associated with worse early post-transplant outcomes. Although MASH-cirrhosis recipients experienced numerically higher event rates, exploratory subgroup analyses did not demonstrate statistically significant differences from the non-MASH recipients. These findings may help refine cardiac risk prediction and perioperative planning, but they do not establish that intensified cardiac risk stratification or perioperative optimization improve outcomes. Prospective studies incorporating detailed cardiac, donor, operative, frailty, and medication data are needed to validate these associations and determine whether targeted risk-stratification and perioperative strategies can improve post-transplant outcomes. Full article

Vitamin A plays an important role in multiple homeostatic functions such as vision, immunity, epithelial cell integrity and differentiation, cell signaling, pulmonary function, reproduction, growth, and development. Vitamin A deficiency was described in people with cystic fibrosis (pwCF) due to a multitude of causes, such as suboptimally managed exocrine pancreatic insufficiency, advanced cystic fibrosis-related liver disease (aCFLD), and a history of intestinal resection, and is generally rare in contemporary practice. Apart from true vitamin A deficiency, low vitamin A levels may also be noted in various inflammatory states, as vitamin A is a negative acute-phase reactant. In the current era of cystic fibrosis (CF) transmembrane-conductance regulator (CFTR)-directed therapies, there is a paradigm shift in vitamin A status, with deficiency statuses becoming rarer, and instead higher serum vitamin levels (in some cases, even in the hypervitaminosis range) are increasingly reported. People with aCFLD, renal insufficiency, post-lung transplantation, and pregnancy are prone to vitamin A toxicity. Hence, CF clinicians should be proactive in evaluating these abnormalities and proficient in managing both deficiency and toxicity, as both these conditions can be associated with adverse outcomes. In this review, we detailed the basics of vitamin A metabolism, manifestations of both vitamin A deficiency and excess, and their clinical implications in pwCF. Full article

Background: Malakoplakia is a rare chronic granulomatous inflammatory disorder characterized by defective macrophage phagolysosomal activity and accumulation of Michaelis–Gutmann bodies on histopathology. It occurs predominantly in immunocompromised individuals and may mimic infectious, inflammatory, or neoplastic processes, creating significant diagnostic challenges. We describe four cases of malakoplakia occurring in distinct immunocompromised states and review the published literature to better characterize its clinical spectrum, management, and outcomes. Methods: We conducted a retrospective case series of four patients diagnosed with histologically confirmed malakoplakia at our institution. Cases occurred in the setting of liver transplantation, kidney transplantation, relapsed acute myeloid leukemia, and ulcerative colitis treated with immunosuppressive therapy. A literature review was performed using PubMed and Google Scholar to identify published cases of malakoplakia in immunocompromised hosts. Demographic, clinical, microbiological, therapeutic, and outcome data were extracted and analyzed descriptively. Results: Four patients with malakoplakia involving the gastrointestinal tract or renal allograft were identified. Clinical presentations ranged from incidental endoscopic findings and tumor-like colonic masses to recurrent bacteremia and graft dysfunction. Histopathologic examination demonstrated characteristic Michaelis–Gutmann bodies in all cases. Management included antimicrobial therapy, observation, and surgical intervention when necessary. Two patients achieved complete clinical and histologic resolution, one required transplant nephrectomy because of persistent allograft infection, and one died from progressive acute myeloid leukemia. Combined with 48 cases identified in the literature, 52 patients were analyzed. The gastrointestinal tract was the most frequently affected site (76.9%), followed by the genitourinary tract (19.2%). Malignancy (32.7%), solid-organ transplantation (26.9%), and autoimmune disease (21.2%) were the most common underlying conditions. Conclusions: Malakoplakia should be considered in the differential diagnosis of mass lesions, persistent infections, and inflammatory lesions in immunocompromised patients, particularly those with malignancy or receiving immunosuppressive therapy. Early histopathologic diagnosis is essential to distinguish malakoplakia from malignancy and guide appropriate management. Our findings highlight the heterogeneous clinical manifestations and outcomes of this uncommon condition and emphasize the importance of multidisciplinary evaluation in affected patients. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to Western dietary patterns. Yet, preclinical studies rely on continuous high-fat feeding, overlooking the intermittent nature of human eating. Whether dietary periodicity itself influences the gut–liver axis and MASLD pathogenesis remains unknown. We compared continuous and intermittent high-fat, high-cholesterol (HFHC) diets in guinea pigs, a model that mirrors human lipoprotein metabolism, hepatic cholesterol handling, and hindgut fermentation. Methods: Integrated multi-omics analyses (serum metabolomics, fecal 16S rRNA sequencing, and liver transcriptomics) were employed in a guinea pig model, stratified into normal diet (ND), intermittent HFHC diet (IHD), and IHD with flaxseed lignan supplementation, to compare the effects of dietary regimens and the therapeutic efficacy of lignan on hepatic pathology. Results: Both diets induced hallmark hepatic features of MASLD; however, the intermittent regimen provoked significantly more severe hepatic steatosis, inflammation, oxidative stress, and fibrosis. Hepatic transcriptomic analysis identified the PI3K-Akt signaling pathway as the most significantly enriched pathway in the IHD group. Mechanistically, this aggravated liver injury was linked to gut microbiota dysbiosis and a marked depletion of the microbial metabolite enterolactone. Fecal microbiota transplantation confirmed that the dysbiotic microbiota directly transmits the aggravated liver injury phenotype. Supplementation with flaxseed lignan, the dietary precursor of enterolactone, restored enterolactone production, corrected the dysregulated gut microbiota–enterolactone axis, and largely normalized the expression of PI3K-Akt downstream targets, thereby alleviating hepatic pathology. Conclusions: These findings suggest that alterations in the gut microbiota–enterolactone axis may contribute to diet-periodicity-driven liver injury and highlight its potential involvement in disease progression. Modulating this axis through dietary interventions, such as flaxseed lignan supplementation, may represent a promising nutritional strategy for mitigating MASLD associated with cyclical dietary exposure. Full article

Primary sclerosing cholangitis (PSC) is a rare cholangiopathy strongly associated with inflammatory bowel disease (IBD), particularly ulcerative colitis. PSC-IBD defines a clinically quiescent but biologically aggressive colitis phenotype, characterized by extensive yet often asymptomatic mucosal inflammation and disproportionately elevated risks of colorectal cancer—approximately 3- to 5-fold higher than in IBD alone—and cholangiocarcinoma (CCA), with IBD comorbidity representing an independent risk factor for hepatopancreatobiliary malignancy. The pathogenesis remains incompletely understood but involves genetic susceptibility, immune dysregulation—including aberrant lymphocyte trafficking and an imbalance between T helper 17 (Th17) and regulatory T (Treg) cells—intestinal barrier dysfunction, and gut–liver axis perturbations involving alterations in the microbiota and bile acid homeostasis. Within the biliary tree, chronic inflammation activates peribiliary glands (PBGs), which harbor stem/progenitor cells. PBG hyperplasia may contribute to periductal fibrosis through Hedgehog signaling and epithelial-to-mesenchymal transition and may represent a key step in PSC-associated cholangiocarcinogenesis. The true burden of PSC-IBD is likely underestimated, as PSC may remain clinically silent for years. Bidirectional screening is therefore essential: all patients with PSC should undergo ileocolonoscopy with biopsies regardless of symptoms, whereas patients with IBD and cholestatic liver biochemistry—particularly elevated gamma-glutamyl transferase or alkaline phosphatase—should undergo magnetic resonance cholangiopancreatography. No medical therapy has demonstrated a clear ability to alter the natural history of PSC, and liver transplantation remains the only definitive treatment for advanced disease. This review integrates current evidence on the epidemiology, pathophysiology, and management of PSC-IBD, critically examining unmet needs in timely diagnosis, mechanistic understanding, and therapeutic development, with particular attention to non-invasive biomarkers, microbiota-directed strategies, individualized risk stratification, and disease-modifying endpoints. Full article

Background: The use of hepatitis B surface antigen-positive (HBsAg+) kidneys may expand the donor pool for transplantation. This study evaluated the incidence, risk factors, complications, organ function, and survival outcomes of transplants from HBsAg+ donors to HBsAg− recipients. Methods: A systematic search of five databases was conducted through 20 August 2023. Incidence was expressed with 95% confidence intervals (CIs); odds ratios (ORs) and hazard ratios (HRs) assessed risk factors and survival. Results: Sixteen studies were included. Donor-derived HBV infection occurred in 3.60% (21/583). Risk was higher in HBsAb-negative (OR: 6.67, 95% CI: 1.08–41.10) and HBcAb-negative recipients (OR: 12.96, 95% CI: 2.06–81.69). Abnormal liver function occurred in 35.18%, hepatitis in 3.07%, and hepatic failure in 0.84%. Liver and kidney function at 1–3 years were comparable between HBsAg+ and HBsAg− kidney recipients. Five- and ten-year graft survival (85.2%, 82.7%) and patient survival (93.0%, 91.4%) were similar to controls (p > 0.05). Conclusions: HBsAg+ kidneys can achieve acceptable long-term outcomes with appropriate antiviral prophylaxis and cautious recipient selection, though infection risk requires careful assessment. These findings supports the cautious and selective use of HBsAg-positive kidneys in appropriately selected recipients use and standardized HBV prophylaxis. Full article

Background: Volumetric evaluation is critical in living donor liver transplantation. Liver volume, depending on body weight and height, and radiological estimates have made important contributions, but some inconsistencies remain. We aimed to assess the estimated and radiological liver volumes with respect to actual graft weight and potential factors contributing to inaccuracy. Method: A total of 623 donors were evaluated in this retrospective study. The estimated liver volumes were calculated with the Vauthey formula. The laboratory and liver biopsy results were obtained. Three-dimensional liver tomography was used to assess liver volume. Actual graft weight was measured on the back table after perfusion. Graft types were recorded. A discrepancy of more than 10% is accepted as discordant. The possible reasons were evaluated. Results: The mean estimated liver volume and radiological liver volume were 1216 cm³ and 1290 cm³, respectively. The mean radiological right lobe volume and the actual right lobe graft weight were 815 and 846, respectively. Liver density, liver steatosis percentage, blood cholesterol levels, blood triglyceride levels, and blood total bilirubin levels are factors contributing to the disparity between the estimated and radiological volume differences. Vitamin B12 and albumin levels were associated with the discrepancy between radiological liver volume and actual graft weight. Underestimation was significant in the left lateral lobe. Conclusions: Three-dimensional volumetry is useful for size matching. Discrepancies of more than 10% are attributable to liver steatosis or splitting lines. Full article

Background/Objectives: The HALP score is a simple immunonutritional index calculated from routine preoperative hemoglobin, albumin, lymphocyte, and platelet values. We evaluated its association with mortality after liver transplantation for non-malignant indications and its prognostic contribution when considered with the Model for End-stage Liver Disease (MELD) score. Methods: We retrospectively analyzed 194 adults who underwent liver transplantation for non-malignant disease at a single center between January 2015 and January 2025. The primary outcome was all-cause post-transplant death. The cohort-derived HALP threshold was used for exploratory Kaplan–Meier and Cox analyses, while continuous HALP was examined in sensitivity analyses. Censoring-adjusted cumulative/dynamic ROC analyses evaluated discrimination at 30 days, 90 days, 1 year, and 3 years. Results: Over a median observed follow-up of 1108 days, 43 recipients (22.2%) died. Non-survivors had lower HALP values than survivors [0.52 (0.39–0.67) vs. 0.77 (0.54–1.04); p < 0.001]. HALP had the highest observed conventional AUC among the evaluated markers for overall mortality (AUC 0.735; 95% CI 0.657–0.814); pairwise AUC differences were not formally tested. The exploratory threshold was 0.6786. Mortality occurred in 36.3% of the low-HALP group and 9.7% of the high-HALP group. After adjustment for MELD and albumin, high versus low HALP remained associated with lower mortality (HR 0.239; 95% CI 0.116–0.493; p < 0.001). HALP also showed consistent time-dependent discrimination across the four evaluated horizons (AUC 0.713–0.738). Conclusions: Lower preoperative HALP was associated with higher post-transplant mortality in this non-malignant liver transplant cohort. HALP may provide complementary risk information, but the cohort-derived threshold requires independent external validation before clinical use. Full article

Background: Static cold storage (SCS) remains the conventional standard for liver graft preservation; however, ischemia–reperfusion injury during storage may contribute to graft dysfunction, particularly with extended criteria and marginal donors. Machine perfusion (MP) has emerged as a promising alternative, yet existing systematic reviews are limited by their focus on individual perfusion modalities or selected donor populations. We performed a comprehensive systematic review and meta-analysis with pre-specified modality-specific subgroup analyses comparing all MP strategies with SCS in adult liver transplantation. Methods: This study was conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (CRD420261355605). MEDLINE, Embase, and PubMed were systematically searched for comparative studies published between 2015 and 2025. Primary outcomes were early allograft dysfunction (EAD), primary non-function (PNF), and 1-year graft survival. Secondary outcomes included biliary complications, hepatic artery thrombosis (HAT), and postoperative transaminase levels. Pre-specified subgroup analyses were performed according to perfusion modality (NMP versus HMP/HOPE). Results: A total of 1448 records were identified. After removal of 309 duplicates and screening, 21 studies comprising 3665 patients were included. Compared with SCS, MP was associated with a significantly lower risk of EAD (RR 0.67, 95% CI 0.48–0.94; p = 0.020), PNF (RR 0.31, 95% CI 0.11–0.84; p = 0.020), and graft loss at one year (RR 0.54, 95% CI 0.36–0.81; p = 0.003; I² = 0%). Subgroup analysis demonstrated that reductions in EAD and PNF were driven by HMP/HOPE strategies (EAD: RR 0.66, 95% CI 0.45–0.98; PNF: RR 0.23, 95% CI 0.07–0.79), whereas NMP did not achieve statistical significance for these endpoints. No significant differences were observed in biliary complications or HAT. Conclusions: Machine perfusion is associated with improved early graft function, reduced primary non-function, and superior 1-year graft survival compared with static cold storage. The benefit for early graft outcomes is driven by hypothermic strategies. These findings provide modality-specific evidence to guide preservation strategy selection in clinical practice. Full article

Liver transplantation (LT) has evolved from a treatment for end-stage benign liver disease into a therapeutic strategy for selected oncological indications, including hepatocellular carcinoma (HCC), unresectable colorectal liver metastases (CRLM), hepatoblastoma, neuroendocrine tumor hepatic metastases, and hepatic epithelioid hemangioendothelioma. As the indications for LT expand and post-transplant survival improves, pulmonary recurrence has emerged as the predominant pattern of extrahepatic relapse across histologies. Yet no standardized surgical guidelines exist for managing lung metastases in the post-transplant patient. This narrative review synthesizes the available evidence on pulmonary metastasectomy following LT, addressing the incidence and tumor-specific patterns of pulmonary recurrence, the influence of immunosuppression on metastatic biology, surgical indications and contraindications, approach and timing considerations, and patient selection across primary histologies. We propose a practical decision-making framework integrating primary tumor biology, disease-free interval, lesion characteristics, immunosuppression regimen, and systemic therapy response. With the recent regulatory recognition of CRLM as a standard transplant indication and the ongoing SECA-III randomized trial, the downstream surgical management of pulmonary recurrence in LT recipients requires urgent evidence-based codification. Full article

Background/Objectives: The developmental origins of health and disease (DOHaD) theory suggests that intrauterine and early postnatal life represents a critical window for programming lifelong health trajectories and disease susceptibility in offspring. Maternal nutritional imbalance during this period is closely associated with obstetric complications and an elevated risk of metabolic disorders in children. As central metabolic hubs, mitochondria constitute a critical axis linking adverse in utero exposure to metabolic defects in offspring across generations. Methods: In this narrative review, we searched PubMed and Web of Science (up to 8 July 2026) for English-language literature linking maternal metabolic conditions and mitochondrial dysfunction. We included in vivo, in vitro, and clinical studies, explicitly excluding primary inherited mtDNA mutations and nonnutritional toxicant exposures to isolate nutritional programming effects. Results: Maternal metabolic stress induces multifaceted, tissue-specific mitochondrial alterations in the developing offspring. Rather than a uniform systemic decline, mitochondrial reprogramming exhibits profound spatial and cellular heterogeneity across critical metabolic organs, including the placenta, liver, skeletal muscle, heart, and hypothalamus. These developmental adaptations often manifest as molecular compensations, such as altered mitochondrial dynamics, perturbed biogenesis, and shifted OXPHOS capacity, ultimately leading to functional bioenergetic failure, oxidative stress, and the establishment of insulin resistance. Discussion: Organ-specific mitochondrial dysfunction drives the maternal transmission of metabolic syndrome. Targeting these mechanisms via dietary modifications, exercise, pharmacological agents, and mitochondrial transplantation offers promising strategies to rescue bioenergetics and prevent metabolic diseases in offspring. Full article