Association of lipid profile and obesity in patients with polycystic ovary syndrome.

Objective. Abnormal lipid profile and obesity increase the risk of polycystic ovary syndrome (PCOS). PCOS patients may have a greater risk of infertility, metabolic syndrome (MetS) and cardiovascular disease (CVD) due to abnormal lipid profile and obesity. The aim of the study was to find the association between abnormal lipid profile and obesity in patients with PCOS. Methods. In this case-control study, a total of 102 female subjects (51 diagnosed PCOS and 51 age-matched healthy controls) were enrolled, aged between 20-40 years. Biochemical parameters such as total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), very low-density lipoprotein-cholesterol (VLDL-C), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were estimated. Anthropometric parameters such as body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) were recorded. A p<0.05 was considered statistically significant. Results. Mean of BMI, WC, WHR, LH, FSH, TC, TG, LDL-C, and VLDL-C was found significantly elevated in patients with PCOS as compared to controls (p<0.01). However, the mean of HDL-C was found significantly reduced in patients with PCOS as compared to controls (p<0.01). BMI has shown a significant positive correlation with WC (r=0.562, p<0.01) and WHR (r=0.580, p<0.01) among PCOS patients. LH has shown a significant positive correlation with FSH (r=0.572, p<0.01) among PCOS patients. TC has shown a significant positive correlation with TG (r=0.687, p<0.01), LDL-C (r=0.917, p<0.01), and VLDL-C (r=0.726, p<0.01) among PCOS patients. Conclusion. The results showed that abnormal lipid profile and obesity have a significant association with PCOS patients. Regular monitoring and treatment of PCOS patients are required to reduce the risk of infertility, MetS, and CVD.

Evolution of coherence singularities in polarization singular beams.

The evolution of correlation singularities in partially coherent polarization singular beams (PC-PSBs) is investigated. Since PSBs are the superposition of two orthogonally polarized vortex beams, the occurrence of coherence singularities in PC-PSBs is strongly governed by the topological charge of the component vortex beams and the spatial coherence length. Coherence singularities appear in the form of ring dislocations in the modulus of the spectral degree of coherence (SDoC) profile, and the number of ring dislocations is equal to the higher value of the topological charge of the superposing vortex beam. Furthermore, the SDoC phase profile can be used to determine the polarity of a PC-PSB. The findings of the study could be valuable in various applications that rely on the spatial coherence of beams, such as free-space communication and imaging.

Monocyte migration profiles define disease severity in acute COVID-19 and unique features of long COVID.

BACKGROUND: COVID-19 is associated with a dysregulated immune response but it is unclear how immune dysfunction contributes to the chronic morbidity persisting in many COVID-19 patients during convalescence (long COVID). METHODS: We assessed phenotypical and functional changes of monocytes in COVID-19 patients during hospitalisation and up to 9 months of convalescence following COVID-19, respiratory syncytial virus or influenza A. Patients with progressive fibrosing interstitial lung disease were included as a positive control for severe, ongoing lung injury. RESULTS: Monocyte alterations in acute COVID-19 patients included aberrant expression of leukocyte migration molecules, continuing into convalescence (n=142) and corresponding with specific symptoms of long COVID. Long COVID patients with unresolved lung injury, indicated by sustained shortness of breath and abnormal chest radiology, were defined by high monocyte expression of C-X-C motif chemokine receptor 6 (CXCR6) (p<0.0001) and adhesion molecule P-selectin glycoprotein ligand 1 (p<0.01), alongside preferential migration of monocytes towards the CXCR6 ligand C-X-C motif chemokine ligand 16 (CXCL16) (p<0.05), which is abundantly expressed in the lung. Monocyte CXCR6 and lung CXCL16 were heightened in patients with progressive fibrosing interstitial lung disease (p<0.001), confirming a role for the CXCR6-CXCL16 axis in ongoing lung injury. Conversely, monocytes from long COVID patients with ongoing fatigue exhibited a sustained reduction of the prostaglandin-generating enzyme cyclooxygenase 2 (p<0.01) and CXCR2 expression (p<0.05). These monocyte changes were not present in respiratory syncytial virus or influenza A convalescence. CONCLUSIONS: Our data define unique monocyte signatures that define subgroups of long COVID patients, indicating a key role for monocyte migration in COVID-19 pathophysiology. Targeting these pathways may provide novel therapeutic opportunities in COVID-19 patients with persistent morbidity.

Novel Models for Accurate Estimation of Air-Blood Partitioning: Applications to Individual Compounds and Complex Mixtures of Neutral Organic Compounds.

The air-blood partition coefficient (Kab) is extensively employed in human health risk assessment for chemical exposure. However, current Kab estimation approaches either require an extensive number of parameters or lack precision. In this study, we present two novel and parsimonious models to accurately estimate Kab values for individual neutral organic compounds, as well as their complex mixtures. The first model, termed the GC×GC model, was developed based on the retention times of nonpolar chemical analytes on comprehensive two-dimensional gas chromatography (GC×GC). This model is unique in its ability to estimate the Kab values for complex mixtures of nonpolar organic chemicals. The GC×GC model successfully accounted for the Kab variance (R2 = 0.97) and demonstrated strong prediction power (RMSE = 0.31 log unit) for an independent set of nonpolar chemical analytes. Overall, the GC×GC model can be used to estimate Kab values for complex mixtures of neutral organic compounds. The second model, termed the partition model (PM), is based on two types of partition coefficients: octanol to water (Kow) and air to water (Kaw). The PM was able to effectively account for the variability in Kab data (n = 344), yielding an R2 value of 0.93 and root-mean-square error (RMSE) of 0.34 log unit. The predictive power and explanatory performance of the PM were found to be comparable to those of the parameter-intensive Abraham solvation models (ASMs). Additionally, the PM can be integrated into the software EPI Suite, which is widely used in chemical risk assessment for initial screening. The PM provides quick and reliable estimation of Kab compared to ASMs, while the GC×GC model is uniquely suited for estimating Kab values for complex mixtures of neutral organic compounds. In summary, our study introduces two novel and parsimonious models for the accurate estimation of Kab values for both individual compounds and complex mixtures.

Exploring effects of Simvastatin on coagulation mediators to alleviate the advancement of high cholesterol diet triggered neurodegeneration.

The objectives of our study were to investigate the possible effect of Simvastatin in ameliorating high cholesterol diet (HCD)-induced neurodegeneration and to also investigate its possible action on coagulation mediators. In silico and in vitro studies were performed to evaluate the impact of Simvastatin on prime coagulation mediators. HCD was used to induce neuropathology in wistar rats and histopathological and immunohistochemical studies were performed to evaluate the efficacy of Simvastatin in preventing the advancement of neurodegeneration in obese rats. Biochemical analyses were used to estimate changes in lipid profile, oxidative stress, inflammatory and coagulation markers. Simvastatin showed good theoretical affinity to coagulation proteins, significantly reversed changes in inflammatory and coagulation biomarkers which were induced by HCD. Enhanced fibrinolytic activity of Simvastatin was revealed through in vitro analysis. Immunohistoanalysis showed raised level of Nrf2. Histopathological studies also supported neuroprotective potential of Simvastatin in HCD fed rats. Simvastatin demonstrated reduced hypercoagulation, enhanced fibrinolysis and reversed neurodegeneration in HCD exposed rats suggesting its potential role in preventing the progression of neurodegeneration in obesity.

Role of adipokines (omentin and visfatin) in coronary artery disease.

AIMS: Adipose tissue is considered as an endocrine organ that releases bioactive factors known as adipokines which contribute to the pathogenesis of rotundity-linked metabolic and cardiovascular complications. Rotundity is a major predisposer for the development and progression of coronary artery disease (CAD). DATA SYNTHESIS: The literature survey from various databases such as Pubmed/Medline, DOAJ, Scopus, Clarivate analytics/Web of Science and Google Scholar were used to prepare this article. The epidemic of rotundity has gained significant attention to understand the biology of adipocytes and the metabolism of adipose tissue in obese individuals. In CAD, visfatin/NAMPT was primarily indicated as a clinical marker of atherosclerosis, endothelial dysfunction and vascular injury having a prognostic significance. Visfatin/NAMPT is a factor that promotes vascular inflammation and atherosclerosis. Omentin is an anti-inflammatory and anti-atherogenic adipokine regulating cardiovascular functions. CONCLUSIONS: This review highlights and summarizes the scientific information pertaining to the role of the adipokines - omentin and visfatin in CAD.

The role of kisspeptin in the pathogenesis of a polycystic ovary syndrome.

Hypothalamic-pituitary gonadal (HPG) axis is responsible for the development and regulation of the female reproductive system. In polycystic ovary syndrome (PCOS), there is a disturbance in the HPG axis. Kisspeptin, a neuropeptide produced by the KISS1 gene, plays a vital role in the regulation of HPG axis by binding with its receptors KISS1R/GPR54, and stimulates gonadotropin secretion from the hypothalamus into pituitary to release luteinizing hormone (LH) and follicle stimulating hormone (FSH). Polymorphisms or mutations in the KISS1 gene can cause disturbance in the kisspeptin signaling pathway and is thought to disrupt HPG axis. Altered signaling of kisspeptin can cause abnormal secretion of GnRH pulse, which leads to increased LH/FSH ratio, thereby affecting androgen levels and ovulation. The increased levels of androgen worsen the symptoms of PCOS. In the present article, we review the molecular physiology and pathology of kisspeptin and how it is responsible for the development of PCOS. The goal of this review article is to provide an overview and metabolic profile of kisspeptin in PCOS patients and the expression of kisspeptin in PCOS animal models. In the present article, we also review the molecular physiology and pathology of kisspeptin and how it is responsible for the development of PCOS.

Evaluation of serum adipokines (omentin-1 and visfatin) in coronary artery disease at a North Indian hospital.

Objective. Adipose tissue is considered to be an endocrine organ that secretes bioactive substances known as adipokines that contribute to the pathophysiology of metabolic and coronary diseases related to obesity. In this study, various novel biomarkers, such as inflammatory markers that are pro-inflammatory (visfatin) and anti-inflammatory (omentin-1), as prognostic indicators for people with coronary artery disease (CAD) were investigated. Methods. In this study, 30 diabetic patients with CAD, 30 diabetic patients without CAD, and 30 healthy control counterparts were included. Serum omentin and visfatin concentrations were evaluated by solid-phase enzyme linked immunosorbent assay (ELISA) kit. Patients with established diagnosis of CAD based on angiography, ECG, and elevated cardiac marker level were included into the study. Patients with cardioembolic stroke, cerebral venous sinus thrombosis, CNS vasculitis, and hemorrhage due to trauma, tumor, vascular malformation, and coagulopathy were excluded. Results. The serum omentin-1 levels were significantly higher in the healthy controls in comparison with the diabetic group (p<0.0001) and serum visfatin levels were significantly higher in the diabetic group in comparison with the healthy controls (p<0.0001). The serum omentin levels were significantly higher in the diabetic group in comparison with the cardio-diabetic group (p<0.0001) and serum visfatin levels were significantly higher in the cardio-diabetic group in comparison with the diabetic group (p<0.0001). The serum omentin-1 showed negative correlation with the serum visfatin in the cardio-diabetic group. Conclusion. The adipokines, such as omentin and visfatin, may be good therapeutic candidates in preventing or ameliorating CAD.

Targeting hypercoagulation to alleviate Alzheimer's disease progression in metabolic syndrome.

INTRODUCTION: Metabolic Syndrome (MetS) constitutes an important risk factor for Alzheimer's disease (AD); however, the mechanism linking these two disorders has not been completely elucidated. Hence, hypercoagulation may account for the missing hallmark connecting MetS and AD. The present review proposes how hemostatic imbalance triggered in MetS advances in the context of AD. MetS causes interruption of insulin signaling and inflammation, inciting insulin resistance in the brain. Subsequently, neuroinflammation and brain endothelial dysfunction are prompted that further intensify the exorbitant infiltration of circulating lipids and platelet aggregation, thereby causing hypercoagulable state, impairing fibrinolysis and eventually inducing prothrombic state in the brain leading to neurodegeneration. OBJECTIVE: This study aims to understand the role of hypercoagulation in triggering the progression of neurodegeneration in MetS. It also offers a few interventions to prevent the progression of AD in MetS targeting hypercoagulation. METHODS: Literature studies based on MetS related neurodegeneration, the impact of coagulation on aggravating obesity and AD via the mechanisms of BBB disruption, neuroinflammation, and hypofibrinolysis. CONCLUSION: The present paper proposes the hypothesis that hypercoagulation might amplify MetS associated insulin resistance, neuroinflammation, BBB disruption, and amyloid beta accumulation which eventually leads to AD.

Investigation of partially coherent vector vortex beams with non-isotropic states of spatial correlation.

In this work, the far-field properties of non-isotropic partially coherent vector vortex beams (PCVVBs) are investigated both theoretically and experimentally. The term non-isotropic signifies that the spatial correlations between the parallel and orthogonal electric field components are distinguishable. It is found that self-orientation and shaping of intensity profile, correlation-induced polarization and depolarization are highly dependent on both the non-isotropic correlation parameters and Poincaré-Hopf index (PHI) of the beam. The simultaneous depolarization and polarization effects are due to the difference in the input correlation parameters that alter the state of polarization (SOP) and degree of polarization (DOP) distributions. The experimental results are in good agreement with the theoretical predictions. The distinguishability of correlation parameters at the source plane leads to significant changes on its intensity profile, DOP, and SOP distributions on far-field propagation, which may found potential applications in beam shaping, detecting and imaging atmospheric lidar, optical imaging and directional transportation where the self-rotation characteristic of beam plays an important role.

Coherence-induced depolarization effects in polarization singular beams.

We demonstrate theoretically and experimentally coherence-induced depolarization effects in generic and higher index polarization singular beams endowed with C-point (or V-point) polarization singularity. The irradiance profiles and degree of polarization (DoP) distributions are found to be governed by spatial coherence length, polarization singularity index, and orbital angular momentum (OAM) of the superposition states of the beams. On reducing the coherence length, the DoP distribution in the V-point deteriorates uniformly. In contrast, C-point beams resist depolarization exhibiting anti-depolarization around the central core of the beam due to the nonzero net OAM of the beam. Interestingly, the polarization vortex structure remains preserved on reducing the spatial coherence length.

Carotid doppler indices do not predict fluid responsiveness in mechanically ventilated patients undergoing coronary artery bypass grafting surgery.

BACKGROUND AND AIM OF THE STUDY: This study aimed to determine the predictive value of carotid artery blood flow (CABF), corrected carotid flow time (CFT), and respiratory variation in carotid peak systolic velocity (DVPeakCA) for fluid responsiveness in mechanically ventilated patients undergoing coronary artery bypass grafting (CABG) surgery. It also aimed to correlate each of these indices with changes in stroke volume index (SVI) after a fluid bolus. METHODS: This prospective, interventional, before-after study recruited 45 adult patients undergoing CABG. Following induction of anesthesia, a fluid challenge of 6 ml/kg of a crystalloid solution was delivered over 10 min. Mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), CABF, CFT, and DVPeakCA were recorded before and following the intervention. Patients with an increase in SVI of >15% from baseline were considered responders. RESULTS: We had 22 responders and 23 nonresponders. Areas under the receiver operating characteristic (AUROC) curves for the studied indices (CABF, 0.516, CFT, 0.502, and DVPeakCA, 0.671) did not suggest any strong predictive value to detect fluid responsiveness. Similarly, the r values for correlation of these carotid doppler-derived indices, both baseline and as % change from baseline with the % alteration of SVI were all <0.2, which demonstrates a very weak correlation between these variables. CONCLUSIONS: Carotid doppler indices are unreliable to assess fluid responsiveness, and cannot replace invasive methods of analyzing preload optimization. There was no significant correlation between carotid doppler-derived indices and alterations in SVI before and after the fluid bolus.

Awareness, screening, practices and attitudes of cervical cancer among doctors and nursing staff working at a tertiary care centre.

Objectives: To assess knowledge, attitude and practice of medical and paramedical staff about cervical cancer as well as its screening and prevention. METHODS: The descriptive cross-sectional study was conducted at the Jinnah Post-graduate Medical Centre, Karachi, from March 1 to August 30, 2019, and comprised women medical and paramedical staff randomly selected from different specialties. Data was collected using a structured questionnaire. Data was analysed using SPSS 20. RESULTS: Of the 347 participants 144(41.5%) were nurses and 203(58.5%) were doctors. The overall mean age was 26.22±6.38 years. Of the total, 108(30%) respondents were married and 239(68%) were single. Overall, 239(68.8%) were well aware of Pap smear being the screening test; 85(24.5%) were aware of the true guidelines to repeat the test; 152(43.8%) had an idea of the exact use of visual Inspection with acetic acid; 61(17.6%) had got a Pap smear done; and 156(45%) thought they were at risk of developing carcinoma cervix. The common risk factors identified were multiple sexual partners 254(73.2%), age at first sexual intercourse 160(46%), smoking 131(37.8%), foul-smelling discharge 221(63.7%), and post-coital bleeding 231(66.6%). CONCLUSIONS: Cervical cancer prevalence is rising due to inadequate knowledge and awareness among healthcare personals. Improvement can be brought by regular use of Pap smear.

Young's double-slit experiment with vector vortex beams.

In this Letter, Young's double-slit experiment with vector vortex beams is investigated. We present the results for various Poincaré-Hopf index beams of this class considering all four major types. Polarization associated morphological changes in the far-field interference pattern are studied both theoretically and experimentally. The Fraunhofer pattern consists of lattices of polarization singularities of the generic type, located on a line, in a direction perpendicular to the slit. The number of linear lattices varies as a function of Poincaré-Hopf index η of the beam that is diffracted, and the number of intensity nulls occurring along the vertical line is equal to |η|.

Pak2 as a Novel Therapeutic Target for Cardioprotective Endoplasmic Reticulum Stress Response.

RATIONALE: Secreted and membrane-bound proteins, which account for 1/3 of all proteins, play critical roles in heart health and disease. The endoplasmic reticulum (ER) is the site for synthesis, folding, and quality control of these proteins. Loss of ER homeostasis and function underlies the pathogenesis of many forms of heart disease. OBJECTIVE: To investigate mechanisms responsible for regulating cardiac ER function, and to explore therapeutic potentials of strengthening ER function to treat heart disease. METHODS AND RESULTS: Screening a range of signaling molecules led to the discovery that Pak (p21-activated kinase)2 is a stress-responsive kinase localized in close proximity to the ER membrane in cardiomyocytes. We found that Pak2 cardiac deleted mice (Pak2-CKO) under tunicamycin stress or pressure overload manifested a defective ER response, cardiac dysfunction, and profound cell death. Small chemical chaperone tauroursodeoxycholic acid treatment of Pak2-CKO mice substantiated that Pak2 loss-induced cardiac damage is an ER-dependent pathology. Gene array analysis prompted a detailed mechanistic study, which revealed that Pak2 regulation of protective ER function was via the IRE (inositol-requiring enzyme)-1/XBP (X-box-binding protein)-1-dependent pathway. We further discovered that this regulation was conferred by Pak2 inhibition of PP2A (protein phosphatase 2A) activity. Moreover, IRE-1 activator, Quercetin, and adeno-associated virus serotype-9-delivered XBP-1s were able to relieve ER dysfunction in Pak2-CKO hearts. This provides functional evidence, which supports the mechanism underlying Pak2 regulation of IRE-1/XBP-1s signaling. Therapeutically, inducing Pak2 activation by genetic overexpression or adeno-associated virus serotype-9-based gene delivery was capable of strengthening ER function, improving cardiac performance, and diminishing apoptosis, thus protecting the heart from failure. CONCLUSIONS: Our findings uncover a new cardioprotective mechanism, which promotes a protective ER stress response via the modulation of Pak2. This novel therapeutic strategy may present as a promising option for treating cardiac disease and heart failure.

Coherence-induced polarization effects in vector vortex beams.

We demonstrate theoretically and experimentally coherence-induced polarization changes in higher-order vector vortex beams (VVBs) with polarization singularity. The prominent depolarization on decreasing the transverse correlation width in a focused partially coherent VVB provides a means to shape the intensity profile and degree of polarization (DOP) while preserving the polarization distribution. The intensity variation and DOP dip are found to be dependent on the polarization singularity index of the beam. Our results may provide an additional degree of freedom in myriad applications presently projected with VVBs.

Upcoming diagnostic biomarkers with promising prospects in neurological disorders.

An exponential increase in the prevalence of neurological disorders requires substantial steps to be taken for their prevention and treatment. Neurodiagnostic biomarkers are gaining momentum presently in order to enhance the diagnostic accuracy of neurodegenerative disorders, to precisely assess their advancement and to monitor the efficiency of therapeutic interventions. Therefore, the primary focus of the present review is the recent development in this field of neurodiagnostic biomarkers, and the current state of biomarker exploration in the context of various neurodegenerative diseases. This review encompasses an updated and detailed account of specific (ß-Amyloid, Tau and Phospho-tau 181, Tar-DNA binding protein-43, Progranulin, a-synuclein, Clusterin, etc) and non-specific (genetic, synaptic, inflammatory and coagulation) neurodiagnostic biomarkers and the recent advances in this growing field. This comprehensive review also suggests the utilization of neurodiagnostic markers in network approaches and personalized medication that will eventually improvise the existing diagnostic and therapeutic complexities of neurodiagnostic biomarkers.

Riluzole-loaded nanoparticles to alleviate the symptoms of neurological disorders by attenuating oxidative stress.

Purpose: The objective of the research undertaken was to develop the Riluzole (RIZ) nanoparticles drug delivery system using Transferrin (Tf) as a ligand in the brain.Method: RIZ-loaded chitosan nanoparticles and RIZ-Tf chitosan (CS) nanoparticles (RIZ CSNPs and RIZ-Tf CSNPs) were formulated and compared for particles size, size distribution, encapsulation efficiency, and surface morphology, respectively. The in vitro drug release, permeation, pharmacokinetic, biochemical, and pharmacodynamic experiments were done to assess the improvement in in vivo fate and efficacy of RIZ.Results: The size of optimized RIZ CSNPs was found to be 173.6 ± 2.23 nm and polydispersity index (PDI) of 0.264 ± 0.002 while that of RIZ-Tf CSNPs was 207 ± 2.49 nm and 0.406 ± 0.002. In vitro release was found to be 86.15 ± 7.316% and 91.1 ± 5.836%, respectively, while permeability coefficient was found to be 4 × 10-2 and 4.2 × 10-2 cm/s for RIZ CSNPs and RIZ-Tf CSNPs. The biochemical analysis studies revealed that oxidative stress was significantly decreased in case of RIZ CSNPs and RIZ-Tf CSNPs (p < 0.01) treated groups. The antianxiety effect and the memory restoration were evident in pharmacodynamic studies (p < 0.05) of the prepared formulations.Conclusion: The results of pharmacokinetic studies demonstrated the remarkable brain delivery of RIZ-Tf CSNPs through intranasal route as compared to the RIZ solution.

Helicity conservation in V-point diffraction.

In singular beams, topological charge is conserved during diffraction. Like scalar field diffraction, in vector field diffraction also, there are conserved quantities. A diffracting V-point disintegrates into a number of C-points of the same polarity in which the polarization singularity index is conserved. In this Letter, we show for the first time, to the best of our knowledge, that apart from the index, the helicity (handedness) is also conserved in V-point diffraction. Since V-point is devoid of any handedness, the helicity conservation entails that there is an equal number of opposite handed C-points in the diffracted field, which are interestingly also found to be orthogonal pairs. Further, coexistence of C-points of opposite handedness in the diffraction demands the presence of L-line, which is also shown. We experimentally demonstrate these by studying the diffraction phenomenon through two different types of apertures.

SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine.

The Sir2 family of enzymes or sirtuins are known as nicotinamide adenine dinucleotide (NAD)-dependent deacetylases and have been implicated in the regulation of transcription, genome stability, metabolism and lifespan. However, four of the seven mammalian sirtuins have very weak deacetylase activity in vitro. Here we show that human SIRT6 efficiently removes long-chain fatty acyl groups, such as myristoyl, from lysine residues. The crystal structure of SIRT6 reveals a large hydrophobic pocket that can accommodate long-chain fatty acyl groups. We demonstrate further that SIRT6 promotes the secretion of tumour necrosis factor-α (TNF-α) by removing the fatty acyl modification on K19 and K20 of TNF-α. Protein lysine fatty acylation has been known to occur in mammalian cells, but the function and regulatory mechanisms of this modification were unknown. Our data indicate that protein lysine fatty acylation is a novel mechanism that regulates protein secretion. The discovery of SIRT6 as an enzyme that controls protein lysine fatty acylation provides new opportunities to investigate the physiological function of a protein post-translational modification that has been little studied until now.