Hormones and B-cell development in health and autoimmunity.

The development of B cells into antibody-secreting plasma cells is central to the adaptive immune system as they induce protective and specific antibody responses against invading pathogens. Various studies have shown that, during this process, hormones can play important roles in the lymphopoiesis, activation, proliferation, and differentiation of B cells, and depending on the signal given by the receptor of each hormone, they can have a positive or negative effect. In autoimmune diseases, hormonal deregulation has been reported to be related to the survival, activation and/or differentiation of autoreactive clones of B cells, thus promoting the development of autoimmunity. Clinical manifestations of autoimmune diseases have been associated with estrogens, prolactin (PRL), and growth hormone (GH) levels. However, androgens, such as testosterone and progesterone (P4), could have a protective effect. The objective of this review is to highlight the links between different hormones and the immune response mediated by B cells in the etiopathogenesis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). The data collected provide insights into the role of hormones in the cellular, molecular and/or epigenetic mechanisms that modulate the B-cell response in health and disease.

Overview of the expression patterns and roles of Lipocalin 2 in the reproductive system.

The 25 kDa-sized protein Lipocalin 2 (LCN2) was originally isolated from human neutrophil granulocytes more than 30 years ago. LCN2 is an emerging player in innate immune defense, as it reduces bacterial growth due to its ability to sequester iron-containing bacterial siderophores. On the other hand, LCN2 also serves as a transporter for various hydrophobic substances due to its ß-barrel shaped structure. Over the years, LCN2 has been detected in many other cell types including epithelial cells, astrocytes, and hepatocytes. Studies have clearly shown that aberrant expression of LCN2 is associated with a variety of disorders and malignancies, including several diseases of the reproductive system. Furthermore, LCN2 was proposed as a non-invasive prognostic and/or diagnostic biomarker in this context. Although several studies have shed light on the role of LCN2 in various disorders of the female and male reproductive systems, including tumorigenesis, a comprehensive understanding of the physiological function of LCN2 in the reproductive tract is still lacking. However, there is evidence that LCN2 is directly related to fertility, as global depletion of Lcn2 in mice has a negative effect on their pregnancy rate. Since LCN2 expression can be regulated by steroid hormones, it is not surprising that its expression fluctuates greatly during remodeling processes in the female reproductive tract, especially in the uterus. Well-founded details about the expression and regulation of LCN2 in a healthy reproductive state and also about possible changes during reproductive aging could contribute to a better understanding of LCN2 as a target in various diseases. Therefore, the present review summarizes current knowledge about LCN2 in the reproductive system, including studies in rodents and humans, and discusses changes in LCN2 expression during pathological events. The limited data suggest that LCN2 is expressed and regulated differently in healthy male and female reproductive organs.

Perilipin 5 deletion protects against nonalcoholic fatty liver disease and hepatocellular carcinoma by modulating lipid metabolism and inflammatory responses.

The molecular mechanisms underlying the transition from nonalcoholic fatty liver disease (NAFLD) to hepatocellular carcinoma (HCC) are incompletely understood. During the development of NAFLD, Perilipin 5 (PLIN5) can regulate lipid metabolism by suppressing lipolysis and preventing lipotoxicity. Other reports suggest that the lack of PLIN5 decreases hepatic injury, indicating a protective role in NAFLD pathology. To better understand the role of PLIN5 in liver disease, we established mouse models of NAFLD and NAFLD-induced HCC, in which wild-type and Plin5 null mice were exposed to a single dose of acetone or 7,12-dimethylbenz[a]anthracene (DMBA) in acetone, followed by a 30-week high-fat diet supplemented with glucose/fructose. In the NAFLD model, RNA-seq revealed significant changes in genes related to lipid metabolism and immune response. At the intermediate level, pathways such as AMP-activated protein kinase (AMPK), signal transducer and activator of transcription 3 (STAT3), c-Jun N-terminal kinase (JNK), and protein kinase B (AKT) were blunted in Plin5-deficient mice (Plin5-/-) compared to wild-type mice (WT). In the NAFLD-HCC model, only WT mice developed liver tumors, while Plin5-/- mice were resistant to tumorigenesis. Furthermore, only 32 differentially expressed genes associated with NALFD progession were identified in Plin5 null mice. The markers of mitochondrial function and immune response, such as the peroxisome proliferator-activated receptor-γ, coactivator 1-α (PGC-1α) and phosphorylated STAT3, were decreased. Lipidomic analysis revealed differential levels of some sphingomyelins between WT and Plin5-/- mice. Interestingly, these changes were not detected in the HCC model, indicating a possible shift in the metabolism of sphingomelins during carcinogenesis.

Analysis of commercially available snake antivenoms reveals high contents of endotoxins in some products.

As injectable therapeutics, snake antivenoms must meet specifications for endotoxin content. The Limulus amebocyte lysate (LAL) test was used to evaluate the endotoxin content in several commercially available antivenoms released for clinical use. It was found that some products have endotoxin concentrations higher than the accepted limit for these contaminants. These results emphasize the need to include endotoxin determination as part of the routine evaluation of antivenoms by manufacturers and regulatory agencies.

Lipid-Independent Regulation of PLIN5 via IL-6 through the JAK/STAT3 Axis in Hep3B Cells.

Perilipin 5 (PLIN5) is a lipid droplet coat protein that is highly expressed in oxidative tissues such as those of muscles, the heart and the liver. PLIN5 expression is regulated by a family of peroxisome proliferator-activated receptors (PPARs) and modulated by the cellular lipid status. So far, research has focused on the role of PLIN5 in the context of non-alcoholic fatty liver disease (NAFLD) and specifically in lipid droplet formation and lipolysis, where PLIN5 serves as a regulator of lipid metabolism. In addition, there are only limited studies connecting PLIN5 to hepatocellular carcinoma (HCC), where PLIN5 expression is proven to be upregulated in hepatic tissue. Considering that HCC development is highly driven by cytokines present throughout NAFLD development and in the tumor microenvironment, we here explore the possible regulation of PLIN5 by cytokines known to be involved in HCC and NAFLD progression. We demonstrate that PLIN5 expression is strongly induced by interleukin-6 (IL-6) in a dose- and time-dependent manner in Hep3B cells. Moreover, IL-6-dependent PLIN5 upregulation is mediated by the JAK/STAT3 signaling pathway, which can be blocked by transforming growth factor-ß (TGF-ß) and tumor necrosis factor-α (TNF-α). Furthermore, IL-6-mediated PLIN5 upregulation changes when IL-6 trans-signaling is stimulated through the addition of soluble IL-6R. In sum, this study sheds light on lipid-independent regulation of PLIN5 expression in the liver, making PLIN5 a crucial target for NAFLD-induced HCC.

Time-of-day defines NAD+ efficacy to treat diet-induced metabolic disease by synchronizing the hepatic clock in mice.

The circadian clock is an endogenous time-tracking system that anticipates daily environmental changes. Misalignment of the clock can cause obesity, which is accompanied by reduced levels of the clock-controlled, rhythmic metabolite NAD+. Increasing NAD+ is becoming a therapy for metabolic dysfunction; however, the impact of daily NAD+ fluctuations remains unknown. Here, we demonstrate that time-of-day determines the efficacy of NAD+ treatment for diet-induced metabolic disease in mice. Increasing NAD+ prior to the active phase in obese male mice ameliorated metabolic markers including body weight, glucose and insulin tolerance, hepatic inflammation and nutrient sensing pathways. However, raising NAD+ immediately before the rest phase selectively compromised these responses. Remarkably, timed NAD+ adjusted circadian oscillations of the liver clock until completely inverting its oscillatory phase when increased just before the rest period, resulting in misaligned molecular and behavioral rhythms in male and female mice. Our findings unveil the time-of-day dependence of NAD+-based therapies and support a chronobiology-based approach.

Prolactin promotes proliferation of germinal center B cells, formation of plasma cells, and elevated levels of IgG3 anti-dsDNA autoantibodies.

Systemic lupus erythematosus (SLE) mainly affects females at reproductive age, which has been associated with hormones, such as prolactin (PRL). Different studies suggest that PRL exacerbates the clinical manifestations of SLE both in patients and in mouse models (e.g., the MRL/lpr strain), increasing the production of autoantibodies, which can be deposited as immune complexes and trigger inflammation and damage to different tissues. The objective of this work was to explore the potential mechanisms by which PRL increases the concentration of self-reactive antibodies in the MRL/lpr SLE model. To this end, we determined the role of PRL on the activation and proliferation of germinal center B cells (B-GCs) and their differentiation into antibody-secreting cells (ASCs). We show that the absolute number and percentage of B-GCs were significantly increased by PRL in vivo or upon in vitro treatment with anti-IgM and anti-CD40 antibodies and PRL. The augmented B-GC numbers correlated with enhanced proliferation, but we did not observe enhanced expression of CD80 and CD86 activation markers or the BCL6 transcription factor, arguing against a more effective differentiation. Nevertheless, we observed enhanced phosphorylation of STAT1, secretion of IL-6, expression of IRF4, numbers of ASCs, and levels of IgG3 antibodies directed against dsDNA. Altogether, these results support the hypothesis that a PRL-mediated expansion of B-GCs yields more self-reactive ASCs, potentially explaining the pathogenic immune complexes that steadily lead to tissue damage during SLE.

The effect of prolactin on immune cell subsets involved in SLE pathogenesis.

The higher frequency of autoimmune diseases in the female population compared to males suggests that certain hormones, such as prolactin (PRL), play a role in determining the prevalence of autoimmunity in women, particularly during childbearing age. PRL can act not only as a hormone but also as a cytokine, being able to modulate immune responses. Hyperprolactinemia has been implicated in the pathogenesis of various autoimmune diseases where it may affect disease activity. One of the conditions where PRL has such a role is systemic lupus erythematosus (SLE). PRL regulates the proliferation and survival of both lymphoid and myeloid cells. It also affects the selection of T-cell repertoires by influencing the thymic microenvironment. In autoimmune conditions, PRL interferes with the activity of regulatory T cells. It also influences B cell tolerance by lowering the activation threshold of anergic B cells. The production of CD40L and cytokines, such as interleukin IL-6, are also promoted by PRL. This, in turn, leads to the production of autoantibodies, one of the hallmarks of SLE. PRL increases the cytotoxic activity of T lymphocytes and the secretion of proinflammatory cytokines. The production of proinflammatory cytokines, particularly those belonging to the type 1 interferon (IFN) family, is part of the SLE characteristic genetic signature. PRL also participates in the maturation and differentiation of dendritic cells, promoting the presentation of autoantigens and high IFNα secretion. It also affects neutrophil function and the production of neutrophil traps. Macrophages and dendritic cells can also be affected by PRL, linking this molecule to the abnormal behavior of both innate and adaptive immune responses.This review aimed to highlight the importance of PRL and its actions on the cells of innate and adaptive immune responses. Additionally, by elucidating the role of PRL in SLE etiopathogenesis, this work will contribute to a better understanding of the factors involved in SLE development and regulation.

Complex spatio-temporal structure of the Holocene Thermal Maximum.

Inconsistencies between Holocene climate reconstructions and numerical model simulations question the robustness of climate models and proxy temperature records. Climate reconstructions suggest an early-middle Holocene Thermal Maximum (HTM) followed by gradual cooling, whereas climate models indicate continuous warming. This discrepancy either implies seasonal biases in proxy-based climate reconstructions, or that the climate model sensitivity to forcings and feedbacks needs to be reevaluated. Here, we analyze a global database of Holocene paleotemperature records to investigate the spatiotemporal structure of the HTM. Continental proxy records at mid and high latitudes of the Northern Hemisphere portray a "classic" HTM (8-4 ka). In contrast, marine proxy records from the same latitudes reveal an earlier HTM (11-7ka), while a clear temperature anomaly is missing in the tropics. The results indicate a heterogeneous response to climate forcing and highlight the lack of globally synchronous HTM.

Perfluorooctane sulfonate and perfluorooctanoic acid induce plasma membrane dysfunction in boar spermatozoa during in vitro capacitation.

Spermatozoa require the capacitation, a series of biochemical events, to perform fertilization. Many toxic compounds can interfere in this process, including perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), which belong to the perfluoroalkyl substances (PFAS). Since both substances are found in many everyday materials and are highly persistent, they accumulate in organisms where they have been associated with fertility problems. This study analyzes the effects of PFOS and PFOA on the functionality of boar spermatozoa, and changes in the plasma membrane (PM) during capacitation. The median lethal concentrations (LC50) of PFOS and PFOA were 460 and 1894 µM, respectively, while the mean inhibitory concentrations of capacitation (ICC50) were 274 µM and 1458 µM, respectively. The ICC50 of PFOA was insufficient to reduce the capacitation, but 950 µM (½ LC50) of PFOA and the ICC50 of PFOS significantly reduced the number of capacitated spermatozoa. PFOS and PFOA also impeded the progesterone (P4)-induced acrosomal reaction (iAR). These effects occur despite the accumulation of [Ca2+]i under capacitating conditions. The accumulation of [Ca2+]i produces saturation, which prevents its entry through ionophore A23187 and P4 in the presence of PFOS. Membrane potential (Emv) was deregulated. Both PFAS affected lipid membrane conductance mediated by valinomycin. The spermatozoa presented 49% and 47% of membrane dysfunction with PFOS and PFOA, respectively. By causing membrane damage, both substances prevented the release of cholesterol and altered the organization of membrane microdomains (MMDs). Data indicate that both PFAS caused alterations in PM functionality.

Nutrition competencies for undergraduate medical education: Results of an international interdisciplinary consensus.

BACKGROUND: The gap between the nutrition education provided to medical students and the nutrition competencies and attitudes needed for physicians to provide adequate nutrition care is a global concern. There is no universally accepted benchmark on nutrition competencies for doctors. The objective of this study was to establish, by expert consensus, the objectives of undergraduate nutrition medial education, the nutrition core competencies, and strategies for curriculum development in medical nutrition education. METHODS: We administered a Delphi survey to systematically gather the opinion of a panel of Latin American experts in nutrition. The survey questionnaire was constructed considering scientific literature by using a 5-point Likert scale. Consensus was defined as >70% agreement on the importance of an item (Likert scale 4 and 5). RESULTS: A four-round Delphi survey was conducted for this research. In the second, third, and fourth rounds, we validated a total of 130 competencies by consensus, which were distributed into four different thematic areas: (1) basic nutrition concepts, (2) public nutrition and nutrition prevention throughout the life cycle, (3) nutrition status and disease, and (4) nutrition care process. CONCLUSION: The curricula for general physician education in medical school must include health promotion, prevention, and treatment of diseases related to nutrition. This goal can be reached by integrating ≤130 competencies into four different fundamental areas.

COVID-19 in children and the influence on the employment activity of their female caregivers: A cross sectional gender perspective study.

Introduction: During the COVID-19 pandemic, women disproportionately assume more unpaid activities, affecting their employment. Objective: Describe the influence of COVID-19 on the employment of caregivers of children and adolescents from a gender perspective. Methods: Cross-sectional study in three high-complexity hospitals in Bogotá, Colombia from April 2020 to June 2021. A subsample of the FARA cohort was taken, including those patients with a positive test for SARS-COV2. We took as our analysis category children older than 8 years and younger than 18 years who had a positive SARS-COV2 test, as well as, caregivers of all children with a positive SARS-COV2 test. This subsample was drawn from the FARA cohort. A survey was applied to them. We carried out a descriptive and stratified analysis by age group, educational, and socioeconomic level. Results: We included 60 surveys of caregivers and 10 surveys of children. The main caregiver in 94.8% of the cases was a female. At the beginning of the pandemic, 63.3% of the caregivers were employed, and 78.9% of those lost their employment. The vast majority of these caregiver were women (96.6%, n = 29). A predominance of loss of work activity was documented in caregivers of children in early childhood 66.6% (n = 20), with lower education 66.6% (n = 20), and from lower strata 56.6% (n = 17). Conclusion: Caregivers of children with COVID-19 with low educational levels and lower socioeconomic conditions, as well as those with children under 5 years showed greater likelihood of employment loss between the interviewed subsample.

Nutrition in medical education in Latin America: Results of a cross-sectional survey.

RATIONALE: The gap between the nutrition education provided to medical students and the nutrition competences and attitudes needed for doctors to provide effective nutrition care is a global concern. The goal of this study was to investigate the curricular content on nutrition education in Latin American medical schools and to evaluate the self-perceived knowledge, attitudes, and barriers to nutrition practice of final-year medical students. METHODS: Eighty-five public and private medical schools from 17 Latin American countries were invited to participate in the study. Two close-ended online questionnaires consisting of 25 and 43 questions were sent to medical school directors. Quantitative variables were expressed as frequencies, percentages, mean ± standard deviation, medians, and ranges. RESULTS: A total of 22 (26%) medical school directors responded, of which 11 schools (50%) offered stand-alone mandatory nutrition courses in preclinical and 8 (36%) in clinical years. The mean hours dedicated to nutrition education was 47 (range: 0-150). A total of 1530 of 1630 (94%) students from 12 countries responded. Students' average age was 25 ± 3 years, and 59% were female. Most students agreed that improving patients' health through nutrition (91%) is important and that nutrition counseling and assessment should be part of routine care provided by all physicians (89%), but they lack the level of education and training required to address nutrition-related issues. CONCLUSIONS: Positive attitude and interest in nutrition among final-year medical students is high, but nutrition education is not perceived as sufficient to adequately prepare doctors in the field of nutrition.

Colelitiasis en Remanente vesicular: reporte de caso / Cholelithiasis in gallbladder remnant: case report / Colelitíase em remanescente de vesícula biliar: relato de caso

Los cálculos biliares se encuentran dentro de los motivos de consulta más frecuentes a nivel mundial, la entidad quirúrgica emergente es la colecistitis en el 90-95 % de los casos, la colecistectomía laparoscópica es la opción ideal de tratamiento, la persistencia de sintomatología postoperatoria, inclusive en el transcurrir de los años es frecuente, en este contexto, es preciso mencionar al síndrome post-colecistectomía que es poco reportado en la localidad. Se presenta el caso de paciente masculino de 71 años de edad con antecedente de colecistectomía abierta hace 13 años, que consulta por meteorismo abdominal, dispepsia, leve dolor en hipocondrio derecho. En los exámenes complementarios de imagen, por ecografía de abdomen, se evidencia colelitiasis en muñón vesicular remanente, diagnóstico certificado por resonancia magnética, indicada previamente por facultativo para control de sus comorbilidades, en el cual se da el hallazgo incidental de litiasis vesicular. Se realiza manejo quirúrgico, colecistectomía laparoscópica, sin ninguna complicación. El paciente mostró adecuada evolución postquirúrgica, siendo dado de alta con analgesia y antibioticoterapia.

Gallstones are among the most frequent reasons for consultation worldwide, the emerging surgical entity is cholecystitis in 90-95% of cases, laparoscopic cholecystectomy is the ideal treatment option, the persistence of postoperative symptoms, even in the passing of the years it is frequent, in this context, it is necessary to mention the post-cholecystectomy syndrome that is little reported in the locality. We present the case of a 71-year-old male patient with a history of open cholecystectomy 13 years ago, who consulted for abdominal bloating, dyspepsia, and mild pain in the right hypochondrium. In the complementary imaging tests, by abdominal ultrasound, cholelithiasis is evidenced in the remaining gallbladder stump, a diagnosis certified by magnetic resonance, previously indicated by the physician to control his comorbidities, in which the incidental finding of gallbladder lithiasis occurs. Surgical management is performed, laparoscopic cholecystectomy, without any complications. The patient showed adequate postoperative evolution, being discharged with analgesia and antibiotic therapy.

Os cálculos biliares estão entre os motivos de consulta mais frequentes em todo o mundo, a entidade cirúrgica emergente é a colecistite em 90-95% dos casos, a colecistectomia laparoscópica é a opção de tratamento ideal, a persistência dos sintomas pós-operatórios, mesmo com o passar dos anos é frequente, nesse contexto, é necessário citar a síndrome pós-colecistectomia que é pouco relatada na localidade. Apresentamos o caso de um paciente do sexo masculino de 71 anos com história de colecistectomia aberta há 13 anos, que consultou por dispepsia, dispepsia e dor leve no hipocôndrio direito. Nos exames complementares de imagem, por ultrassonografia abdominal, evidencia-se colelitíase no coto vesicular remanescente, diagnóstico certificado por ressonância magnética, previamente indicado pelo médico para controle de suas comorbidades, em que ocorre o achado incidental de litíase vesicular. O manejo cirúrgico é realizado, colecistectomia laparoscópica, sem complicações. A paciente apresentou evolução pós-operatória adequada, recebendo alta com analgesia e antibioticoterapia.

Arterial thrombosis and intracardiac thrombus as the initial presentation of a recurrent paraganglioma: case report and review of the literature

SUMMARY Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors that result in the uncontrolled release of catecholamines and secondary hypertension. They usually manifest with episodic blood pressure fluctuations, headaches and palpitations. In some cases PPGLs may be asymptomatic until they are detected as a diagnostic approach to other diseases. There have been reports that have associated PPGLs with arterial thrombosis, some with the additional finding of intracardiac thrombi. We present the case of a 21-year-old male Hispanic patient with a recurrent para-aortic paraganglioma detected by persistent hypertension, bilateral lower limb artery thrombosis and an intracardiac thrombus.

Understanding the Role of Perilipin 5 in Non-Alcoholic Fatty Liver Disease and Its Role in Hepatocellular Carcinoma: A Review of Novel Insights.

Consumption of high-calorie foods, such as diets rich in fats, is an important factor leading to the development of steatohepatitis. Several studies have suggested how lipid accumulation creates a lipotoxic microenvironment for cells, leading cells to deregulate their transcriptional and translational activity. This deregulation induces the development of liver diseases such as non-alcoholic fatty liver disease (NAFLD) and subsequently also the appearance of hepatocellular carcinoma (HCC) which is one of the deadliest types of cancers worldwide. Understanding its pathology and studying new biomarkers with better specificity in predicting disease prognosis can help in the personalized treatment of the disease. In this setting, understanding the link between NAFLD and HCC progression, the differentiation of each stage in between as well as the mechanisms underlying this process, are vital for development of new treatments and in exploring new therapeutic targets. Perilipins are a family of five closely related proteins expressed on the surface of lipid droplets (LD) in several tissues acting in several pathways involved in lipid metabolism. Recent studies have shown that Plin5 depletion acts protectively in the pathogenesis of liver injury underpinning the importance of pathways associated with PLIN5. PLIN5 expression is involved in pro-inflammatory cytokine regulation and mitochondrial damage, as well as endoplasmic reticulum (ER) stress, making it critical target of the NAFLD-HCC studies. The aim of this review is to dissect the recent findings and functions of PLIN5 in lipid metabolism, metabolic disorders, and NAFLD as well as the progression of NAFLD to HCC.

Cannabis for medical and scientific purposes: the Colombian landscape / Panorama del cannabis con fines médicos y científicos en Colombia

Abstract The Colombian government, through Law 1787 of 2016, has created a regulatory framework that allows its citizens to have a safe and informed access to cannabis and its derivatives for medical and scientific purposes. Our country joins others in their efforts to legalize cannabis-derived substances for therapeutic purposes, as many jurisdictions have recognized the potential these products have in the treatment of certain medical conditions. This paper describes the current medical cannabis outlook in Colombia, compares the different medical cannabis supply systems in other parts of the world, summarizes the evidence related to the potential therapeutic benefits and potential risks of using cannabis for medical purposes.

Resumen Mediante la Ley 1787 de 2016, el Gobierno colombiano creó el marco regulatorio que permite el acceso seguro e informado al uso médico y científico del cannabis y sus derivados en nuestro territorio. Este movimiento hacia la legalización de sustancias derivadas de cannabis con fines terapéuticos se suma a otros instaurados en otros países que han reconocido el posible potencial que tienen estos productos en el tratamiento de ciertas condiciones clínicas. Este artículo describe la situación actual del cannabis medicinal en Colombia, compara los diferentes sistemas de provisión de cannabis con fines médicos en otras jurisdicciones, resume la evidencia alrededor de su utilización con fines médicos que justifica la legalización, y los potenciales riesgos que existen con el uso del cannabis.

A Scoping Review on Lipocalin-2 and Its Role in Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma.

Excess calorie intake and a sedentary lifestyle have made non-alcoholic fatty liver disease (NAFLD) one of the fastest growing forms of liver disease of the modern world. It is characterized by abnormal accumulation of fat in the liver and can range from simple steatosis and non-alcoholic steatohepatitis (NASH) to cirrhosis as well as development of hepatocellular carcinoma (HCC). Biopsy is the golden standard for the diagnosis and differentiation of all NAFLD stages, but its invasiveness poses a risk for patients, which is why new, non-invasive ways of diagnostics ought to be discovered. Lipocalin-2 (LCN2), which is a part of the lipocalin transport protein family, is a protein formally known for its role in iron transport and in inflammatory response. However, in recent years, its implication in the pathogenesis of NAFLD has become apparent. LCN2 shows significant upregulation in several benign and malignant liver diseases, making it a good candidate for the NAFLD biomarker or even a therapeutic target. What makes LCN2 more interesting to study is the fact that it is overexpressed in HCC development induced by chronic NASH, which is one of the primary causes of cancer-related deaths. However, to this day, neither its role as a biomarker for NAFLD nor the molecular mechanisms of its implication in NAFLD pathogenesis have been completely elucidated. This review aims to gather and closely dissect the current knowledge about, sometimes conflicting, evidence on LCN2 as a biomarker for NAFLD, its involvement in NAFLD, and NAFLD-HCC related pathogenesis, while comparing it to the findings in similar pathologies.