Small Structural Differences in Proline-Rich Decapeptides Have Specific Effects on Oxidative Stress-Induced Neurotoxicity and L-Arginine Generation by Arginosuccinate Synthase.

INTRODUCTION: The proline-rich decapeptide 10c (Bj-PRO-10c; ENWPHPQIPP) from the Bothrops jararaca snake modulates argininosuccinate synthetase (AsS) activity to stimulate L-arginine metabolite production and neuroprotection in the SH-SY5Y cell line. The relationships between structure, interactions with AsS, and neuroprotection are little known. We evaluated the neuroprotective effects of Bj-PRO-10c and three other PROs (Bn-PRO-10a, Bn-PRO-10c > Bn-PRO-10a-MK > Bn-PRO-10a. The structure of PROs and their correlations with enzyme activity revealed that histidine (H5) and glutamine (Q7) in Bj-PRO-10c potentiated their affinity for AsS. CONCLUSIONS: Our investigation provides the first insights into the structure and molecular interactions of PROs with AsS, which could possibly further their neuropharmacological applications.

Infrapopliteal Bypass In Patients On Dialysis: Patency And Survival.

INTRODUCTION: Portugal has one of the highest prevalence of patients on a regular dialysis program. This population has a higher incidence of peripheral arterial disease with higher rates of postoperative morbidity and mortality. Our goal was to compare outcomes between dialysis and non-dialysis patients with chronic limb threatening ischemia (CLTI) submitted to infrapopliteal bypass. MATERIALS AND METHODS: A retrospective single-center study of infrapopliteal bypass for CLTI was performed between 2012 and 2019. Patients were divided in two groups based on dialysis status (group 1 incorporated patients on dialysis). Primary end point was 1-year freedom from CLTI. Secondary end points were limb-salvage, survival and primary (PP) and tertiary patency (TP) rates at 3 years of follow-up. RESULTS: A total of 352 infrapopliteal bypasses were performed in 310 patients with CLTI. Fourteen percent of the revascularizations were performed on dialysis patients (48/352). Median age was 73 years (interquartile range - IQR 15) and 74% (259/352) were male. Median follow-up was 26 months (IQR 42). Overall, 92% (325/352) had tissue loss and 44% (154/352) had some degree of infection. The majority of revascularization procedures were performed with vein grafts (61%, 214/352). The 30-day mortality was 4% (11/310), with no difference between groups (p = 0.627). Kaplan-Meier analysis showed no difference between groups regarding freedom from CLTI (76% vs. 79%; HR 0.96, CI 0.65-1.44, p=0.857), limb-salvage (70% vs. 82%; HR 1.40, CI 0.71-2.78, p=0.327) and survival (62% vs. 64%; HR 1.08, CI 0.60-1.94, p=0.799). PP rates were 39% in group 1 and 64% in group 2 (HR 1.71, CI 1.05-2.79, p=0.030). TP rates were not different between groups (57% and 78%; HR 1.79, CI 0.92-3.47, p=0.082). CONCLUSION: Infrapopliteal bypass for CLTI, on dialysis patients, resulted in lower PP rates. No differences were observed in freedom from CLTI, TP, limb salvage and survival.

Redox proteomics in melanoma cells: An optimized protocol.

Cancer development and progression are intimately related with post-translational protein modifications, e.g., highly reactive thiol moiety of cysteines enables structural rearrangements resulting in redox biological switches. In this context, redox proteomics techniques, such as 2D redox DIGE, biotin switch assay and OxIcat are fundamental tools to identify and quantify redox-sensitive proteins and to understand redox mechanisms behind thiol modifications. Given the great variability in redox proteomics protocols, problems including decreased resolution of peptides and low protein amounts even after enrichment steps may occur. Considering the biological importance of thiol's oxidation in melanoma, we adapted the biotin-switch assay technique for melanoma cells in order to overcome the limitations and improve coverage of detected proteins.

"You only have one mother!": institutional violence in experiences of double motherhood in healthcare. / "Mãe é só uma!": violência institucional nas experiências de dupla maternidade na atenção à saúde.

The objective was to understand experiences of double motherhood during antenatal, childbirth and postpartum healthcare, using a qualitative method involving individual online interviews and asynchronous, online focus groups of cisgender women, mostly in same-sex relationships. The results revealed how these women's experiences of parenting were marginalised, highlighting institutional violence in Brazilian healthcare services, which are presented here in two thematic dimensions: 1) Cisheteronormativity and its impact on experiences of double motherhood; and 2) Institutional violence in healthcare services: from curiosity to LGBTQIA+phobia. It was concluded that cisheteronormativity hinders healthcare for these experiences, especially by rendering the non-gestational mother invisible. This underscores the urgent need to train healthcare personnel, rethink and challenge cisgender and heterosexual norms and promote inclusive policies to ensure equitable care and combat institutional violence.

Objetivou-se compreender as experiências de dupla maternidade na atenção à saúde durante o pré-natal, parto e puerpério a partir de um método qualitativo, utilizando entrevistas individuais on-line e grupo focal on-line assíncrono com mulheres cisgêneros, a maioria em relacionamentos homoafetivos. Os resultados revelaram a marginalização das vivências parentais dessas mulheres, destacando a violência institucional presente nos serviços de saúde brasileiros, sendo apresentados em dois eixos temáticos: 1) Cisheteronormatividade e seu impacto nas experiências de dupla maternidade e 2) Violência institucional nos serviços de saúde: da curiosidade à LGBTQIA+fobia. Conclui-se que a cisheteronormatividade prejudica a atenção à saúde para essas experiências, especialmente ao invisibilizar a mãe não gestante, destacando a urgência de capacitar profissionais de saúde, repensar e desafiar as normas cisgênero e heterossexuais e promover políticas inclusivas para garantir cuidados equitativos e combater a violência institucional.

Adipose tissue macrophages secrete small extracellular vesicles that mediate rosiglitazone-induced insulin sensitization.

The obesity epidemic continues to worsen worldwide, driving metabolic and chronic inflammatory diseases. Thiazolidinediones, such as rosiglitazone (Rosi), are PPARγ agonists that promote 'M2-like' adipose tissue macrophage (ATM) polarization and cause insulin sensitization. As ATM-derived small extracellular vesicles (ATM-sEVs) from lean mice are known to increase insulin sensitivity, we assessed the metabolic effects of ATM-sEVs from Rosi-treated obese male mice (Rosi-ATM-sEVs). Here we show that Rosi leads to improved glucose and insulin tolerance, transcriptional repolarization of ATMs and increased sEV secretion. Administration of Rosi-ATM-sEVs rescues obesity-induced glucose intolerance and insulin sensitivity in vivo without the known thiazolidinedione-induced adverse effects of weight gain or haemodilution. Rosi-ATM-sEVs directly increase insulin sensitivity in adipocytes, myotubes and primary mouse and human hepatocytes. Additionally, we demonstrate that the miRNAs within Rosi-ATM-sEVs, primarily miR-690, are responsible for these beneficial metabolic effects. Thus, using ATM-sEVs with specific miRNAs may provide a therapeutic path to induce insulin sensitization.

Spatial-temporal distribution of visceral leishmaniasis in Rio de Janeiro, Brazil, 2001-2020: expansion and challenges.

BACKGROUND: Visceral leishmaniasis results from complex interactions among humans, dogs and environment. Brazil accounts for 97% of cases in the Americas. METHODS: Twenty years (2001-2020) of the endemic disease in the state of Rio de Janeiro were studied. Incidence, lethality, sociodemographic and clinical characteristics were investigated, complemented with spatial methodologies (kernel and clusters). RESULTS: Ninety-seven human cases and 625 dogs were reported. Of the 92 cities, 22 were human endemic areas. The state had a low incidence level (0.6 per 100 000). Lethality was higher compared with the Brazilian average. More than 90% of infections occurred in urban areas. Most cases (66%) occurred in men. The predominant age groups were 0-4 y (28.7%) and 20-39 y (32.9%). Fever (89.5%), splenomegaly (83.2%) and hepatomegaly (76.8%) were the main clinical manifestations. Spatial analysis showed a displacement of the human endemic: in the first decade (2001-2010), cases were concentrated in the Metropolitan region, and in the second decade (2011-2020) in the Médio Paraíba region of the state. Most of the endemic area (56.4%) had canine infections without reported human cases. CONCLUSIONS: Disorderly urbanisation and precarious living conditions favour the transmission of the disease. Changes in the environment and migratory processes contribute to its expansion.

Exosome-Mediated Impact on Systemic Metabolism.

Exosomes are small extracellular vesicles that carry lipids, proteins, and microRNAs (miRNAs). They are released by all cell types and can be found not only in circulation but in many biological fluids. Exosomes are essential for interorgan communication because they can transfer their contents from donor to recipient cells, modulating cellular functions. The miRNA content of exosomes is responsible for most of their biological effects, and changes in exosomal miRNA levels can contribute to the progression or regression of metabolic diseases. As exosomal miRNAs are selectively sorted and packaged into exosomes, they can be useful as biomarkers for diagnosing diseases. The field of exosomes and metabolism is expanding rapidly, and researchers are consistently making new discoveries in this area. As a result, exosomes have great potential for a next-generation drug delivery platform for metabolic diseases.

Urban noise assessment in hospitals: measurements and mapping in the context of the city of Sorocaba, Brazil.

Noise pollution has become a public health problem in several countries worldwide. Noise maps are tools used in many cities, mainly on the European continent. In other regions, they are used in smaller areas, and few studies focus on hospital areas, considered noise-sensitive zones. In this context, this study aimed to perform sound measurements and noise maps for the day and night periods in the surroundings of three hospitals in Sorocaba, Brazil. Sound measurements occurred around the three hospitals based on NBR 10151 and ISO 1996 standards. The noise maps were drawn up using a calculation model based on ISO 9613-2. Results showed that the sound measurement points around the hospitals had levels above those recommended by the Brazilian standard for sensitive areas (LAeq 50 and 45 dB for day and night, respectively). The acoustic maps showed high sound levels on all faces of the hospital buildings, both during the day and at night. The worst scenario concerned the vicinity of the roads with the highest flow and speed of vehicles. We concluded that three different hospitals in the city have high sound levels in their surroundings above the recommended for sensitive areas.

The impact of sputum quality on Xpert positivity in active case-finding for TB.

BACKGROUND: Studies evaluating sputum quality and Xpert® MTB/RIF positivity in the context of active case finding are scarce. We aimed to determine whether sputum quality is associated with Xpert positivity and whether the association differed according to demographic and clinical characteristics.METHODS: A cross-sectional analysis using data from a mass screening programme in Brazilian prisons was conducted from 2017 to 2021. We administered a standardised questionnaire, obtained a chest X-ray and collected a spot sputum sample for Xpert testing. Sputum quality was classified as 'salivary', 'mucoid/mucopurulent' or 'blood-stained'. We used log binomial regressions to estimate the relationship between sputum quality and Xpert positivity, assessing interactions with participant characteristics.RESULTS: Among 4,368 participants for whom sputum quality was assessed, 957 (21.9%) produced salivary specimens, 3,379 (77.4%) had mucoid/mucopurulent sputum and 32 (0.7%) had blood-stained sputum. Xpert positivity was higher among those with mucoid/mucopurulent sputum than among those with salivary samples (12.0% vs. 3.7%). Mucopurulent sputum independently predicted Xpert positivity among individuals with and without symptoms, current smoking and abnormal chest radiographs on CAD4TB.CONCLUSIONS: In our study, sputum appearance independently predicted Xpert positivity, and could be used together with chest X-ray and symptom screening to inform use of Xpert in individual or pooled testing.

Heparin-Bonded Expanded Polytetrafluoroethylene Is a Solution for Infrapopliteal Revascularization in the Absence of an Adequate Autologous Vein Graft.

BACKGROUND: To analyze the outcomes of heparin-bonded expanded polytetrafluoroethylene (HePTFE) graft as an alternative conduit in infrapopliteal revascularization of chronic limb-threatening ischemia (CLTI) in the absence of an autologous vein conduit. METHODS: A single-center retrospective analysis of patients with CLTI submitted to infrapopliteal bypasses with autologous vein graft (VEIN group) or HePTFE graft (HePTFE group) was implemented. Primary end points were freedom from CLTI at 12 months and recurrence of CLTI at 3 years. Secondary end points included freedom from major amputation, amputation-free survival (AFS), survival, and primary (PP) and secondary patency (SP) rates at 3 years of follow-up. RESULTS: A total of 348 limbs submitted to infrapopliteal bypasses, 214 with venous graft and 134 with HePTFE graft, were followed-up for a median of 25 months. Most patients of the HePTFE group were male (69%), with a median age of 76 years (interquartile range [IQR] 15). Fifty-nine percent of the limbs of the HePTFE group had Wound grade ≥2, being 46% of them infected. Eighty-eight percent were GLASS stage III. Freedom from CLTI was not significantly different between HePTFE and VEIN groups (75% vs. 84%, adjusted hazard ratio [aHR] 0.88, confidence interval [CI] 0.66-1.18, P = 0.401). Recurrence of CLTI was higher in the HePTFE group (42% vs.18% at 3 years; aHR 2.82, CI 1.59-5.00, P < 0.001). The VEIN group achieved higher rates of freedom from major amputation (87% vs.69% at 3 years; aHR 2.21, CI 1.31-3.75, P = 0.003) and AFS (59% vs. 37% at 3 years; aHR 1.39, CI 1.02-1.88, P = 0.036), but no significance in survival (aHR 1.10, CI 0.72-1.66, P = 0.667). Patency rates were inferior in the HePTFE group, with 2-year PP and SP rates of 52% vs. 74%, and 76% vs. 90%, respectively (PP: aHR 1.70, CI 1.11-2.59, P = 0.014; SP: aHR 2.51, CI 1.42-4.42, P = 0.001). CONCLUSIONS: Infrapopliteal bypass with autologous vein graft is the gold standard to treat CLTI limbs. HePTFE graft should be regarded as an alternative for complex infrapopliteal revascularization when lacking an autologous vein conduct.

Construções de masculinidades entre pessoas moradoras de rua: uma revisão de escopo / Constructions of masculinity among homeless persons: a scoping review

Resumo Nesta revisão objetivou-se investigar e sintetizar o que há na literatura científica sobre as relações entre as masculinidades e as pessoas moradoras de rua, com enfoque em relações sociais, trajetória e processo saúde-doença. Foi feita uma busca sistemática em dez bases de dados com os descritores: "Masculinities", "Hegemonic Masculinities", "Gender Identity" e "Homeless Persons", "Homeless, Roofless" e "Houseless". Obteve-se 2.459 resultados, com 25 referências finais após aplicação dos critérios de inclusão e exclusão, compostas em grande parte por estudos internacionais. Identificou-se seis temas-chave: Masculinidade enquanto prática performativa nas ruas, Masculinidades e relações de violência nas ruas, Masculinidades entre homens moradores de rua: percepções de liberdade e encarceramento, Paternidade dos homens moradores de rua, Estigmas e deságios no processo de busca pela masculinidade hegemônica nas ruas e Masculinidades como determinante social de saúde nas ruas. A revisão aborda as influências das masculinidades entre a População Moradora de Rua (PMR), destacando sua transversalidade nas vivências e atitudes do grupo, e explora a relação entre masculinidades e violência, os desafios na paternidade e os estigmas ligados à condição de vida nas ruas e impactos na saúde. Conclui-se que as normas sociais relacionadas ao masculino atuam como uma forma de se adaptar as vidas nas ruas, mas influenciam negativamente no processo saúde-doença da PMR, em especial dos homens.

Abstract This study aimed to investigate and synthesize the scientific literature regarding the relationships between masculinities and individuals experiencing homelessness by focusing on social relationships, life trajectories, and the health-disease process. A systematic search was conducted in 10 databases using the following descriptors: "Masculinities," "Hegemonic Masculinities," "Gender Identity," "Homeless Persons," "Homeless, Roofless," and "Houseless." In total, 2459 results were retrieved. Overall, 25 studies remained after the application of inclusion and exclusion criteria, most of which were international studies. This study identified six key themes: 1) Masculinity as a performative practice on the streets, 2) Masculinities and relationships of violence on the streets, 3) Masculinities among men experiencing homelessness: perceptions of freedom and imprisonment, 4) Fatherhood among men experiencing homelessness, 5) Stigmas and challenges in the pursuit of hegemonic masculinity on the streets, and 6) Masculinities as a social determinant of health on the streets. This review addresses the influences of masculinities on individuals experiencing homelessness, emphasizing the cross-cutting nature of these ideals in the experiences and attitudes of this group. It explores the relationship between masculinities and violence, as well as addressing challenges in fatherhood. It highlights stigmas linked to the condition of being homeless that impact health and quality of life. It is concluded that social norms related to masculinity act negatively as social determinants of health for the homeless population, especially men.

"Mãe é só uma!": violência institucional nas experiências de dupla maternidade na atenção à saúde / "You only have one mother!": institutional violence in experiences of double motherhood in healthcare

Resumo Objetivou-se compreender as experiências de dupla maternidade na atenção à saúde durante o pré-natal, parto e puerpério a partir de um método qualitativo, utilizando entrevistas individuais on-line e grupo focal on-line assíncrono com mulheres cisgêneros, a maioria em relacionamentos homoafetivos. Os resultados revelaram a marginalização das vivências parentais dessas mulheres, destacando a violência institucional presente nos serviços de saúde brasileiros, sendo apresentados em dois eixos temáticos: 1) Cisheteronormatividade e seu impacto nas experiências de dupla maternidade e 2) Violência institucional nos serviços de saúde: da curiosidade à LGBTQIA+fobia. Conclui-se que a cisheteronormatividade prejudica a atenção à saúde para essas experiências, especialmente ao invisibilizar a mãe não gestante, destacando a urgência de capacitar profissionais de saúde, repensar e desafiar as normas cisgênero e heterossexuais e promover políticas inclusivas para garantir cuidados equitativos e combater a violência institucional.

Abstract The objective was to understand experiences of double motherhood during antenatal, childbirth and postpartum healthcare, using a qualitative method involving individual online interviews and asynchronous, online focus groups of cisgender women, mostly in same-sex relationships. The results revealed how these women's experiences of parenting were marginalised, highlighting institutional violence in Brazilian healthcare services, which are presented here in two thematic dimensions: 1) Cisheteronormativity and its impact on experiences of double motherhood; and 2) Institutional violence in healthcare services: from curiosity to LGBTQIA+phobia. It was concluded that cisheteronormativity hinders healthcare for these experiences, especially by rendering the non-gestational mother invisible. This underscores the urgent need to train healthcare personnel, rethink and challenge cisgender and heterosexual norms and promote inclusive policies to ensure equitable care and combat institutional violence.

Secondary metabolites related to the resistance of Psidium spp. against the nematode Meloidogyneenterolobii.

The guava tree (Psidium guajava) is a tropical species native to South America and is recognized as the 11th most economically important fruit tree in Brazil. However, the presence of the nematode Meloidogyne enterolobii and the fungus Fusarium solani in the roots of guava plants leads to the development of root galls, causing significant damage. In contrast, the species P. guineense and P. cattleianum have been identified as resistant and immune to the nematode, respectively. In this study, the researchers aimed to compare the metabolomic profiles of infected and uninfected roots of P. guajava, P. cattleianum, and P. guineense using mass spectrometry coupled with liquid chromatography (LC-MS). The goal was to identify secondary metabolites that could potentially be utilized as biochemical resources for nematode control. The findings of the study demonstrated that the plant metabolism of all three species undergoes alterations in response to the phytopathogen inoculation. By employing molecular networks, the researchers identified that the secondary metabolites affected by the infection, whether produced or suppressed, are primarily of a polar chemical nature. Further analysis of the database confirmed the polar nature of the regulated substances after infection, specifically hydrolysable tannins and lignans in P. guineense and P. cattleianum. Interestingly, a group of non-polar substances belonging to the terpene class was also identified in the resistant and immune species. This suggests that these terpenes may act as inhibitors of M. enterolobii, working as repellents or as molecules that can reduce oxidative stress during the infection process, thus enhancing the guava resistance to the nematode. Overall, this study provides valuable insights into the metabolic alterations occurring in different Psidium spp. in response to M. enterolobii infection. The identification of specific secondary metabolites, particularly terpenes, opens up new possibilities for developing effective strategies to control the nematode and enhance guava resistance.

Application of spatial environmental indicators in the assessment of degradation potential of water resources in water basins.

Changes in land use have been occurring in a continuous and disorderly way in recent decades due to rapid population growth and the growing demand for food. These constant changes result in a series of harmful effects to the environment, especially to water resources, significantly changing their availability and quality. This study aims to evaluate the degradation potential of watersheds through an evaluation of some environmental indicators using arithmetic means to construct an index called in this research "index of potential environmental degradation" (IPED). To form the IPED, the hydrographic sub-basins of the Sorocabuçu River, located in the central west of the State of São Paulo, Brazil, comprised the study area. The results showed that most hydrographic sub-basins, that is, eight units, present degradation values ranging from moderate to very high, resulting mainly from low conservation values of forests plus a use destined to the planting of temporary cultures depending on good physical conditions. On the other hand, only one sub-basin showed a low degradation value. The methodology used for the development of the IPED is easy to apply and an effective tool for environmental analyses. It may contribute to studies and forms of planning and land use management aiming the conservation of water resources and protected areas and reduction of degradation.

Gut lumen-leaked microbial DNA causes myocardial inflammation and impairs cardiac contractility in ageing mouse heart.

Emerging evidence indicates the critical roles of microbiota in mediating host cardiac functions in ageing, however, the mechanisms underlying the communications between microbiota and cardiac cells during the ageing process have not been fully elucidated. Bacterial DNA was enriched in the cardiomyocytes of both ageing humans and mice. Antibiotic treatment remarkably reduced bacterial DNA abundance in ageing mice. Gut microbial DNA containing extracellular vesicles (mEVs) were readily leaked into the bloodstream and infiltrated into cardiomyocytes in ageing mice, causing cardiac microbial DNA enrichment. Vsig4+ macrophages efficiently block the spread of gut mEVs whereas Vsig4+ cell population was greatly decreased in ageing mice. Gut mEV treatment resulted in cardiac inflammation and a reduction in cardiac contractility in young Vsig4-/- mice. Microbial DNA depletion attenuated the pathogenic effects of gut mEVs. cGAS/STING signaling is critical for the effects of microbial DNA. Restoring Vsig4+ macrophage population in ageing WT mice reduced cardiac microbial DNA abundance and inflammation and improved heart contractility.

Iron Uptake Controls Trypanosoma cruzi Metabolic Shift and Cell Proliferation.

(1) Background: Ionic transport in Trypanosoma cruzi is the object of intense studies. T. cruzi expresses a Fe-reductase (TcFR) and a Fe transporter (TcIT). We investigated the effect of Fe depletion and Fe supplementation on different structures and functions of T. cruzi epimastigotes in culture. (2) Methods: We investigated growth and metacyclogenesis, variations of intracellular Fe, endocytosis of transferrin, hemoglobin, and albumin by cell cytometry, structural changes of organelles by transmission electron microscopy, O2 consumption by oximetry, mitochondrial membrane potential measuring JC-1 fluorescence at different wavelengths, intracellular ATP by bioluminescence, succinate-cytochrome c oxidoreductase following reduction of ferricytochrome c, production of H2O2 following oxidation of the Amplex® red probe, superoxide dismutase (SOD) activity following the reduction of nitroblue tetrazolium, expression of SOD, elements of the protein kinase A (PKA) signaling, TcFR and TcIT by quantitative PCR, PKA activity by luminescence, glyceraldehyde-3-phosphate dehydrogenase abundance and activity by Western blotting and NAD+ reduction, and glucokinase activity recording NADP+ reduction. (3) Results: Fe depletion increased oxidative stress, inhibited mitochondrial function and ATP formation, increased lipid accumulation in the reservosomes, and inhibited differentiation toward trypomastigotes, with the simultaneous metabolic shift from respiration to glycolysis. (4) Conclusion: The processes modulated for ionic Fe provide energy for the T. cruzi life cycle and the propagation of Chagas disease.

An Epithelioid Hemangioma Camouflaged As Radial Aneurysm.

Epithelioid hemangioma (EH) is an uncommon benign vascular lesion usually present as subcutaneous nodules in the head and neck area. Sometimes, these lesions can occur in the peripheral arteries, and when they do, they can be mistaken for aneurysmal dilatations of that respective vessel. We report a case of a 43-year-old male who underwent surgical recession of a radial aneurysm, which after anatomopathological examination, revealed an EH.

Fructose-1,6-bisphosphatase is a nonenzymatic safety valve that curtails AKT activation to prevent insulin hyperresponsiveness.

Insulin inhibits gluconeogenesis and stimulates glucose conversion to glycogen and lipids. How these activities are coordinated to prevent hypoglycemia and hepatosteatosis is unclear. Fructose-1,6-bisphosphatase (FBP1) is rate controlling for gluconeogenesis. However, inborn human FBP1 deficiency does not cause hypoglycemia unless accompanied by fasting or starvation, which also trigger paradoxical hepatomegaly, hepatosteatosis, and hyperlipidemia. Hepatocyte FBP1-ablated mice exhibit identical fasting-conditional pathologies along with AKT hyperactivation, whose inhibition reversed hepatomegaly, hepatosteatosis, and hyperlipidemia but not hypoglycemia. Surprisingly, fasting-mediated AKT hyperactivation is insulin dependent. Independently of its catalytic activity, FBP1 prevents insulin hyperresponsiveness by forming a stable complex with AKT, PP2A-C, and aldolase B (ALDOB), which specifically accelerates AKT dephosphorylation. Enhanced by fasting and weakened by elevated insulin, FBP1:PP2A-C:ALDOB:AKT complex formation, which is disrupted by human FBP1 deficiency mutations or a C-terminal FBP1 truncation, prevents insulin-triggered liver pathologies and maintains lipid and glucose homeostasis. Conversely, an FBP1-derived complex disrupting peptide reverses diet-induced insulin resistance.