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To investigate the relationships between dental anxiety, Facebook intrusion, and shame.A sample of 498 adults aged 16-69 years completed an online questionnaire comprising the Modified Dental Anxiety Scale, the Facebook Intrusion Scale, and the Shame scale from the Test of Self-Conscious Affect.Dental anxiety was positively associated with Facebook intrusion. There were also indirect effects of dental anxiety on Facebook intrusion through shame.The results highlight the problem of dental anxiety in the context of Facebook intrusion risk. The findings may be applicable in Internet dependency prevention and treatment, focused on help in coping with the anxiety related to doctors' appointments.

Standard treatment for chronic lymphocytic leukemia (CLL) has experienced a dramatic change over the last few years. Until recently, CLL was treated using chemoimmunotherapy (CIT) with anti-CD20 monoclonal antibodies. Even though novel agents such as BTKi (Bruton Tyrosine Kinase inhibitor) and BCL2 inhibitors are the standard of care in most therapeutic settings, CIT still has its place in CLL treatment. Interestingly, little is known about its effects on the immune system of patients with CLL. Contrary to the reduction of the number of CLL cells during CIT administration, little attention has been paid to the cellular microenvironment, the evaluation of which during treatment may provide additional information about the course of the disease and prognosis and therefore was set as the aim of this study.Flow cytometry was used to evaluate the phenotypes of different populations and subpopulations of lymphocytes in the peripheral blood (PB) of 20 patients with CLL before, during, and after CIT.During the CIT with R-FC (Rituximab, Fludarabine, and Cyclophosphamide) and R-B (Rituximab, Bendamustine) regimens, the sizes of the assessed populations and subpopulations of lymphocytes were dramatically reduced. Twenty-eight days after the first course of treatment, the exponential decrease of CLL cells was observed, and their number had declined to the median level of 10% of the numbers observed before the treatment. T cells, NK cells, NKCD56dim, NKT-like, and NKT-like CD56dim also decreased exponentially. After the second treatment course, a decline in the numbers of T, NK, NKCD56dim, NKT-like, and NKT-like CD56dim cells was observed, which were stable until the sixth treatment course. However, the number of NKT-like CD56bright cells decreased to the third course of treatment and then increased. The number of CLL cells in peripheral blood correlated with the number of NKCD56bright cells, influencing the treatment response.Upon CIT, the reduction of CLL cells is accompanied by shifts in immune cell populations, T, NK, and NKT-like cells. Monitoring changes of those cell populations in the peripheral blood may serve as an important predictive and prognostic indicator.

Introduction The worldwide outbreak of morbid obesity forced contemporary medicine to adopt a multidisciplinary approach, which led to the description of metabolic syndrome (MS): a disease with self-aggravating components and one of the most important causes of morbidity and mortality. The need for therapeutic methods provoked development of metabolic surgery, which nowadays give possibilities for safe and effective treatment of all MS aspects simultaneously and improves many obesity-related comorbidities. Aim To assess the laparoscopic sleeve gastrectomy (LSG) procedure's efficiency in resolving MS components, treating comorbidities and to analyze the influence on certain biochemical markers in 1-year follow-up. Material and methods The retrospective cohort study of 211 patients after an LSG operation relied on statistical analysis of clinical data collected prospectively in follow-up visits. All applicable guidelines and bioethical recommendations were respected in this study. Results Assessment of bariatric efficiency proved the LSG operation to be effective in inducing significant weight loss and treating obesity. Analysis on the influence on MS components, such as non-insulin dependent diabetes (NIDDM), arterial hypertension (AH) and dyslipidemia, showed substantial improvement in all observed cases of these diseases. In the present study, follow-up also proved a partial remission inducing effect of this bariatric operation in many comorbidities, especially in chronic obstructive pulmonary disease, obstructive sleep apnea, peptic ulcer disease and depression. A desirable reduction in creatinine, C-reactive protein, uric acid, alanine aminotransferase, asparagine aminotransferase, γ-glutamyltransferase serum levels has also been observed during the follow-up. Conclusions The LSG is an effective method of treatment in all areas of metabolic syndrome, provides a significant positive clinical outcome in obesity-related comorbidities and induces desirable changes in inflammatory, kidney and liver related biomarkers.

Our purpose here is to compare the protection against insider trading in Brazil and the European Union law, specifically the way insider trading is sanctioned in these two jurisdictions. We highlight the different compositions between administrative and criminal sanctions found in the two systems and their implications for the fundamental rights and personal rights (in case of Brazil) of those held liable for the practice of insider trading. The possible cumulation of punishments imposed by criminal courts and administrative regulatory bodies raise the question whether there might be a violation of the ne bis in idem principle. The response to that question is different in each system. We will start by briefly taking stock of the genesis and evolution of anti-insider trading regulation in Brazil and in the EU in order to comprehend the different rationales for the prohibition of insider trading in the two jurisdiction, so as to understand the reasons behind their divergencies and convergencies. Nuestro propósito aquí es comparar la protección contra el uso de información privilegiada en Brasil y la ley de la Unión Europea, específicamente la forma en que se sanciona el uso de información privilegiada en estas dos jurisdicciones. Destacamos las diferentes composiciones entre sanciones administrativas y penales encontradas en los dos sistemas y sus implicaciones para los derechos fundamentales y los derechos de la personalidad (en el caso de Brasil) de los responsables por la práctica del uso de información privilegiada. La posible acumulación de sanciones impuestas por los tribunales penales y los órganos reguladores administrativos plantea la cuestión de si podría haber una violación del principio ne bis in idem. La respuesta a esa pregunta es diferente en cada sistema. Comenzaremos revisando brevemente la génesis y evolución de la regulación sobre el uso de información privilegiada en Brasil y en la UE con el fin de comprender las diferentes razones de la prohibición del uso de información privilegiada en ambas jurisdicciones con el fin de comprender las razones detrás de sus diferencias y convergencias. Nosso objetivo aqui é comparar a proteção contra insider trading no Brasil e na União Europeia, especificamente a maneira como o insider trading é sancionado nessas duas jurisdições. Destacaremos as diferentes combinações entre sanções administrativas e criminais encontradas nos dois sistemas e suas implicações para os direitos fundamentais e da personalidade (no caso do Brasil) dos responsáveis pela prática de abuso de informação privilegiada. A possível acumulação de punições impostas por tribunais criminais e órgãos reguladores administrativos levanta a questão de saber se pode haver uma violação do princípio ne bis in idem. A resposta a essa pergunta será diferente em cada sistema. Começaremos fazendo um breve balanço da gênese e da evolução da regulamentação sobre uso de informações privilegiadas no Brasil e na UE, a fim de compreender as diferentes razões para a proibição do insider trading nas duas jurisdições de forma a entender os motivos por trás de suas divergências e convergências.

The system of penal law in Poland is complicated. It includes responsibility for crimes, misdemeanours, fiscal crimes and fiscal misdemeanour. Besides, there are administrative offences punishable with very severe sanctions. Their number has been increasing since the 1990s and now they play an important role as an alternative investigation and sanctioning system. They formally belong to administrative law, but their assessment from the perspective of the criteria of ‘criminal charge’ developed in the jurisprudence of the ECtHR allows to treat them as part of criminal law sensu largissimo. Therefore, this form of responsibility is also called administrative-criminal responsibility. This raises the question of the accordance of the rules regarding the administrative-criminal responsibility, belonging to administrative law, with the main criminal law guarantees. The aim of this paper is to present the general character of administrative-criminal responsibility and to evaluate the rules introduced in 2017 from the perspective of the certain safeguards appropriate for criminal responsibility. El sistema punitivo en Polonia es complicado. Incluye responsabilidad por delitos, faltas, infracciones fiscales y faltas fiscales. Además, existen infracciones administrativas que pueden derivar en sanciones muy severas. Su número ha aumentado desde la década de 1990 y ahora desempeñan un papel importante como sistema alternativo de investigación y sanción. Pertenecen formalmente al derecho administrativo, pero su análisis desde el punto de vista de los criterios de 'persecución penal' desarrollados en la jurisprudencia del TEDH permite tratarlas como parte del derecho penal sensu largissimo. Por tanto, esta forma de responsabilidad también se denomina responsabilidad administrativo-penal. Surge, entonces, la cuestión de la conformidad de las normas relativas a la responsabilidad administrativo-penal, pertenecientes al derecho administrativo, con las principales garantías del derecho penal. El propósito del artículo es presentar el carácter general de la responsabilidad administrativo-penal y evaluar las normas introducidas en 2017 desde la perspectiva de algunas salvaguardas específicamente dirigidas a la responsabilidad penal. O sistema punitivo na Polônia é complicado. Inclui a responsabilidade por crimes, contravenções, crimes fiscais e contravenções fiscais. Além disso, existem infrações administrativas que podem acarretar sanções muito severas. Seu número tem aumentado desde a década de 1990 e agora desempenham um papel importante como um sistema alternativo de investigação e sanção. Elas pertencem formalmente ao direito administrativo, mas sua análise do ponto de vista dos critérios de ‘acusação criminal’ desenvolvidos na jurisprudência do TEDH permite tratá-las como parte do direito penal sensu largissimo. Portanto, essa forma responsabilidade também é chamada de responsabilidade administrativo-criminal. Levanta-se, então, a questão da conformidade das normas relativas à responsabilidade administrativo-criminal, pertencentes ao direito administrativo, com as principais garantias do direito penal. O objetivo do artigo é apresentar o caráter geral da responsabilidade administrativo-criminal e avaliar as regras introduzidas em 2017 na perspectiva de algumas salvaguardas voltadas especificamente à responsabilidade criminal.

The occurrence of MYC-negative Burkitt lymphoma (BL) has been discussed for many years. The real frequency of the MYC insertion in MYC-negative BL is still unknown. Fine-needle aspiration biopsies of 108 consecutive patients with clinicopathologically suspected BL (suspBL) were evaluated by flow cytometry, classical cytogenetics, and fluorescence in situ hybridization (FISH). We found 12 cases (11%) without the MYC rearrangement by FISH with a MYC breakapart probe: two patients (1.9%) with cryptic MYC/IGH fusion (finally diagnosed as BL) and 10 patients (9.3%) with 11q gain/loss (finally diagnosed as Burkitt-like lymphoma with 11q aberration). The exact breakpoints of the cryptic MYC/IGH were investigated by next-generation sequencing. The MYC insertions’ breakpoints were identified in PVT1 in the first case, and 42 kb upstream of 5′MYC in the second case. To date, a molecular characterization of the MYC insertion in BL has only been reported in one case. Detailed descriptions of our MYC insertions in a routinely and consecutively diagnosed suspBL cohort will contribute to resolving the issue of MYC negativity in BL. In our opinion, the presence of the MYC insertions in BL and other lymphomas might be underestimated, because routine genetic diagnostics are usually based on FISH only, without karyotyping.

Adipose tissue (AT) is an endocrine organ involved in the management of energy metabolism via secretion of adipokines, hormones, and recently described secretory microvesicles, i.e., exosomes. Exosomes are rich in possible biologically active factors such as proteins, lipids, and RNA. The secretory function of adipose tissue is affected by pathological processes. One of the most important of these is obesity, which triggers adipose tissue inflammation and adversely affects the release of beneficial adipokines. Both processes may lead to further AT dysfunction, contributing to changes in whole-body metabolism and, subsequently, to insulin resistance. According to recent data, changes within the production, release, and content of exosomes produced by AT may be essential to understand the role of adipose tissue in the development of metabolic disorders. In this review, we summarize actual knowledge about the possible role of AT-derived exosomes in the development of insulin resistance, highlighting methodological challenges and potential gains resulting from exosome studies.

Growing tumors avoid recognition and destruction by the immune system. During continuous stimulation of tumor-infiltrating lymphocytes (TILs) by tumors, TILs become functionally exhausted, thus, they become unable to kill tumor cells and to produce certain cytokines and lose their ability to proliferate. This collectively results in the immune escape of cancer cells. Here, we show that breast cancer cells expressing PD-L1 can accelerate exhaustion of persistently activated human effector CD4+ T cells, manifesting in high PD-1 and PD-L1 expression level son T cell surfaces, decreased glucose metabolism genes, strong downregulation of SWI/SNF chromatin remodeling complex subunits, and p21 cell cycle inhibitor upregulation. This results in inhibition of T cell proliferation and reduction of T cell numbers. The RNAseq analysis on exhausted CD4+ T cells indicated strong overexpression of IDO1 and genes encoding pro-inflammatory cytokines and chemokines. Some interleukins were also detected in media from CD4+ T cells co-cultured with cancer cells. The PD-L1 overexpression was also observed in CD4+ T cells after co-cultivation with other cell lines overexpressing PD-L1, which suggested the existence of a general mechanism of CD4+ T cell exhaustion induced by cancer cells. The ChIP analysis on the PD-L1 promoter region indicated that the BRM recruitment in control CD4+ T cells was replaced by BRG1 and EZH2 in CD4+ T cells strongly exhausted by cancer cells. These findings suggest that epi-drugs such as EZH2 inhibitors may be used as immunomodulators in cancer treatment.

This gloss discusses the position of the Court of Justice of the European Union taken in the judgment passed on 20 March 2018 in the case of Luca Menci (C-524/15) in reference to the restrictions of ne bis in idem principle. The main thesis of the Court concerned the admissibility of restrictions of ne bis in idem based on the principle of proportionality as a limitation clause and its accordance with the Convention for the Protection of Human Rights and Fundamental Freedoms. The analysis of the right not to be tried or punished twice in Article 4 Protocol 7 to the European Convention for the Protection of Human Rights and Fundamental Freedoms allows us to formulate opposite conclusions. The application of the balancing test as a limitation clause for ne bis in idem, finds no support in the case-law of the ECtHR too. According to the Author, the position taken in Menci infringes Article 52(3) of the Charter of Fundamental Rights, according to which the meaning and scope of the rights which correspond to rights guaranteed by the Convention for the Protection of Human Rights and Fundamental Freedoms shall be at least be the same.

Objectives Adipose tissue plays a central role in the pathogenesis of insulin resistance (IR) and type 2 diabetes. However, the molecular changes that promote these diseases are not completely understood. Several studies demonstrated that ceramide (Cer) and diacylglycerol (DAG) accumulation in muscle is associated with IR. The aim of this study was to explain whether a high-fat diet (HFD) leads to bioactive lipid accumulation in adipose tissue and how metformin affects the lipid content in adipocytes and the concentration of plasma adipocytokines. Methods The experiments were conducted on male Wistar rats divided into three groups: control, HFD-fed, and HFD-fed and treated with metformin. Cer and DAGs were analyzed by liquid chromatography tandem mass spectrometry. Phosphorylation of hormone-sensitive lipase (HSL) was analyzed by Western blot. Oral glucose tolerance and insulin tolerance tests were also performed. Plasma adiponectin and tumor necrosis factor (TNF)-α concentration were measured by enzyme-linked immunosorbent assay. Results HFD induced IR and elevated DAGs and Cer content in subcutaneous and visceral adipose tissues, which was accompanied by an increased phosphorylation of HSL. Metformin improved insulin sensitivity, decreased Cer and DAG levels, and attenuated the phosphorylation of HSL in both fat depots. Furthermore, we observed a strong correlation between adiponectin (negative) and TNF-α (positive) and bioactive lipids in both fat tissues. Conclusions These results indicated that bioactive lipids accumulation in adipose tissue influences the induction of IR and, at least in part, answered the question of what the insulin-sensitizing effect of metformin at the level of adipose tissue is.

Introduction Laparoscopic sleeve gastrectomy (LSG) is recently a leading method in surgical treatment of morbid obesity. The metabolic outcome of intervention may be a result of many factors such as age, gender, preoperative weight loss and dietary restrictions. Aim To evaluate gender-related differences in the results of LSG in 6-month follow-up. Material and methods The study included 101 patients who underwent LSG at the University Clinical Hospital of Bialystok. Patients were divided and analyzed in 2 groups: males (n = 48) and females (n = 53). The primary analysis included the influence of gender on postoperative weight loss calculated using the percentage of excess weight loss (%EWL) and excess BMI loss (%EBMIL). For secondary outcomes the levels of glucose, insulin, glycated hemoglobin, aspartate transaminase, alanine transaminase, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides and C-reactive protein were analyzed. Results A significant influence of patients' gender was proved for both %EWL (p = 0.026) and %EBMIL (p = 0.001). Females had significantly higher %EWL in 6-month follow-up than males (p = 0.0034). The analysis also showed significantly higher %EBMIL for women at 3 and 6 months observation (p = 0.022 and p < 0.001 respectively). Conclusions Laparoscopic sleeve gastrectomy is an effective method of obesity treatment especially in terms of postoperative weight loss. Females seem to benefit more from the procedure when analyzing the parameters of body mass reduction. However, further research is needed to provide strong evidence of an association between gender and the results of LSG.

(1) Background: T-cell lymphoblastic lymphoma (T-LBL) is extremely rare and highly aggressive, with no practical risk model defined yet. The prognostic value of T-LBL immunological subtypes is still a matterofcontroversy. (2) Methods: We re-evaluated 49 subsequent adult T-LBL patients treated according to the German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia (GMALL) protocols, 05/93 (n = 20) and T-LBL 1/2004 (n = 29), 85.7% of which achieved complete remission (CR). (3) Results: The 5/10-year overall survival (OS) and event-free survival (EFS) were 62%/59% and 48%/43%, respectively. In 96% of patients, flow cytometry analyses defining the WHO 2008 immunophenotypes were available. Cortical, early/pro-T/CD2(−), early/pre-T/CD2(+), and mature subtypes were identified in 59.5%, 19%, 15%, and 6.5% of patients, respectively. Overall, 20% of patients had the early T-cell precursor (ETP)-LBL immunophenotype, as proposed by the WHO 2017 classification. For the early/pro-T/CD2(−) subtype, the five-year OS and EFS were 13% and 13%, while for all the other, non-pro-T subtypes, they were 69% and 67%. By multivariate analysis, only CD2(−) status and age &gt, 35 years emerged as strong, independent factors influencing OS and EFS, while the risk of CR failure was influenced by age only (&gt, 35 years). (4) Conclusions: ETP was non-significant for OS, unless an ultra-high-risk pro-T/CD2(−) subtype was concerned.

Simple Summary T-cell lymphoblastic lymphoma (T-LBL) is extremely rare and aggressive with no practical risk model defined. Considering the controversies over the prognostic value of T-LBL immunological subtypes, we re-evaluated 49 subsequent adult T-LBL patients treated according to the German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia protocols, with 85.7% with complete remissions. To the best of our knowledge, this is the largest study of T-LBL diagnosed by flow-cytometry of the material obtained by fine-needle aspiration biopsy. We show that (1) CD2 status and age are powerful independent prognostic factors influencing overall survival and the risk of treatment failure; (2) the early/pro-T/CD2(−) subtype is associated with extremely poor outcomes; and (3) poor outcomes in ETP vs. non-ETP are strikingly consistent with the pro-T CD2(−) subtype. The lack of CD2 expression in T-LBL emerges as a new marker of an ultra-high-risk of treatment failure. We show here that ETP is a non-uniform entity, where the outcome depends on the CD2 status. Abstract (1) Background: T-cell lymphoblastic lymphoma (T-LBL) is extremely rare and highly aggressive, with no practical risk model defined yet. The prognostic value of T-LBL immunological subtypes is still a matter of controversy. (2) Methods: We re-evaluated 49 subsequent adult T-LBL patients treated according to the German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia (GMALL) protocols, 05/93 (n = 20) and T-LBL 1/2004 (n = 29), 85.7% of which achieved complete remission (CR). (3) Results: The 5/10-year overall survival (OS) and event-free survival (EFS) were 62%/59% and 48%/43%, respectively. In 96% of patients, flow cytometry analyses defining the WHO 2008 immunophenotypes were available. Cortical, early/pro-T/CD2(−), early/pre-T/CD2(+), and mature subtypes were identified in 59.5%, 19%, 15%, and 6.5% of patients, respectively. Overall, 20% of patients had the early T-cell precursor (ETP)-LBL immunophenotype, as proposed by the WHO 2017 classification. For the early/pro-T/CD2(−) subtype, the five-year OS and EFS were 13% and 13%, while for all the other, non-pro-T subtypes, they were 69% and 67%. By multivariate analysis, only CD2(−) status and age > 35 years emerged as strong, independent factors influencing OS and EFS, while the risk of CR failure was influenced by age only (>35 years). (4) Conclusions: ETP was non-significant for OS, unless an ultra-high-risk pro-T/CD2(−) subtype was concerned.

High-fat diet consumption and lack of physical activity are important risk factors for metabolic disorders such as insulin resistance and cardiovascular diseases. Insulin resistance is a state of a weakened response of tissues such as skeletal muscle, adipose tissue, and liver to insulin, which causes an increase in blood glucose levels. This condition is the result of inhibition of the intracellular insulin signaling pathway. Skeletal muscle is an important insulin-sensitive tissue that accounts for about 80% of insulin-dependent glucose uptake. Although the exact mechanism by which insulin resistance is induced has not been thoroughly understood, it is known that insulin resistance is most commonly associated with obesity. Therefore, it is believed that lipids may play an important role in inducing insulin resistance. Among lipids, researchers’ attention is mainly focused on biologically active lipids: diacylglycerols (DAG) and ceramides. These lipids are able to regulate the activity of intracellular enzymes, including those involved in insulin signaling. Available data indicate that physical activity affects lipid metabolism and has a positive effect on insulin sensitivity in skeletal muscles. In this review, we have presented the current state of knowledge about the impact of physical activity on insulin resistance and metabolism of biologically active lipids.

Background The incidence of obesity has been constantly growing and bariatric procedures are considered to be the most effective treatment solution for morbidly obese patients. The results of laparoscopic sleeve gastrectomy (LSG) may differ depending on patient’s age, gender, preoperative body mass index (BMI) and physical activity. Methods The aim of this study was to evaluate age-related differences in the outcome of LSG in terms of weight loss parameters, lipid and carbohydrate profile. The retrospective analysis of 555 patients who had undergone LSG was performed to compare the metabolic outcomes of surgery in individuals Results Overall, 238 males and 317 females (43%/57%) with median age of 43 years and median preoperative BMI of 46.41 (42.06–51.02) kg/m2 were analyzed. Patients in both groups presented significant weight loss at 24 months after the surgery with comparable percentage of total weight loss (40.95% in p = 0.662, p = 0.788 respectively). Patients under 45 years old experienced faster decrease in fasting glucose level that was observed after only 3 months (109 mg/dl to 95 mg/dl in p p = 0.010; 114.8 mg/dl vs. 122 mg/dl, p = 0.002). Younger group of patients also showed superior improvement of triglycerides level. Conclusions LSG results in significant weight loss in all patients regardless age. In turn, superior and faster improvement in lipid and carbohydrate profile is achieved in patients under 45 years old.

Skeletal muscle is an important tissue responsible for glucose and lipid metabolism. High-fat diet (HFD) consumption is associated with the accumulation of bioactive lipids: long chain acyl-CoA, diacylglycerols (DAG) and ceramides. This leads to impaired insulin signaling in skeletal muscle. There is little data on the involvement of DAG in the development of these disorders. Therefore, to clarify this enigma, the gene encoding glycerol-3-phosphate acyltransferase enzyme (GPAT, responsible for DAG synthesis) was silenced through shRNA interference in the gastrocnemius muscle of animals with diet-induced insulin resistance. This work shows that HFD induces insulin resistance, which is accompanied by an increase in the concentration of plasma fatty acids and the level of bioactive lipids in muscle. The increase in these lipids inhibits the insulin pathway and reduces muscle glucose uptake. GPAT silencing through electroporation with shRNA plasmid leads to a reduction in DAG and triacylglycerol (TAG) content, an increase in the activity of the insulin pathway and glucose uptake without a significant effect on ceramide content. This work clearly shows that DAG accumulation has a significant effect on the induction of muscle insulin resistance and that inhibition of DAG synthesis through GPAT modulation may be a potential target in the treatment of insulin resistance.

Obesity is a major risk factor for the development of insulin resistance and type 2 diabetes. The exact mechanism by which adipose tissue induces insulin resistance is still unclear. It has been demonstrated that obesity is associated with the adipocyte dysfunction, macrophage infiltration, and low-grade inflammation, which probably contributes to the induction of insulin resistance. Adipose tissue synthesizes and secretes numerous bioactive molecules, namely adipokines and cytokines, which affect the metabolism of both lipids and glucose. Disorders in the synthesis of adipokines and cytokines that occur in obesity lead to changes in lipid and carbohydrates metabolism and, as a consequence, may lead to insulin resistance and type 2 diabetes. Obesity is also associated with the accumulation of lipids. A special group of lipids that are able to regulate the activity of intracellular enzymes are biologically active lipids: long-chain acyl-CoAs, ceramides, and diacylglycerols. According to the latest data, the accumulation of these lipids in adipocytes is probably related to the development of insulin resistance. Recent studies indicate that the accumulation of biologically active lipids in adipose tissue may regulate the synthesis/secretion of adipokines and proinflammatory cytokines. Although studies have revealed that inflammation caused by excessive fat accumulation and abnormalities in lipid metabolism can contribute to the development of obesity-related insulin resistance, further research is needed to determine the exact mechanism by which obesity-related insulin resistance is induced.