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Diversion of oil sources for biodiesel production has been gaining importance to meet the environmental concerns and energy demand. The free fatty acid (FFA) content of the feedstock is a significant factor in biodiesel production. The FFA values determine the complexity of the biodiesel production. Until date, an experimental procedure has been used to determine the FFA concentration of an oil source; this method is dependent on titration, which is a laborious process involving significant volumes of chemicals. Hence, in the present study, an attempt was made to develop a device for the identification of FFA of the oils. Waste cooking oil samples subjected to wide range of cooking conditions like cooking time, temperature, type of food are collected from different food outlets. Subsequently, the composition of oil samples and the variation in their quality were analysed using gas chromatography flame ionization detector (GC – FID). Biodiesel is prepared from the oil samples through transesterification and the impact of FFA and their respective methyl esters in the quality and properties have been investigated. The properties of biodiesel were determined as per ASTM standards. The study was further extended to correlate the properties of biodiesel with the composition of the oil from which it was derived. The analysis evidently proved the dependence of biodiesel properties on the FFA percentage and the composition of the oil. The results have been further substantiated with the performance and emission characteristics of internal combustion engine fuelled with the prepared biodiesel samples.

The possibility of rapid estimation of moisture, protein, fat, free fatty acid (FFA), and peroxide value (PV) content in peanut kernel was studied by Fourier transform near-infrared spectroscopy (FTNIR) in the diffuse reflectance mode to estimate the nutritional quality of peanut. The moisture, fat, and protein of fresh and damaged seeds of peanuts ranging from 3 to 9 %, 45 to 57 %, and 23 to 27 % respectively, were used for the calibration model building based on partial least squares (PLS) regression. The peanut samples had major peaks at wavenumbers 5308.53, 4954.98, 4464.03, 4070.85, 7475.63, 8230.21, and 6178.13 in per cm. First and second derivate mathematical preprocessing was also applied in order to eliminate multiple baselines for different chemical quality parameters of peanut. The FFA had the lowest value of calibration and validation errors (0.579 and 0.738) followed by the protein (0.736 and 0.765). The quality of peanut seeds with the lowest root mean square error of cross-validation of 0.76 and a maximum correlation coefficient (R2) of 96.8 was obtained. The comprehensive results signify that FT-NIR spectroscopy can be used for rapid, non-destructive quantification of quality parameters in peanuts.

This study evaluates the performance of a continuous microwave device in the sterilization of oil palm fruits spikelet. The device comprises four microwave generators (magnetron), a tunnel cavity driven by a belt conveyor, and a tray as a container for palm fruit. This study aims to evaluate the distribution and penetration of microwave energy into palm fruit and to examine the quality of palm oil concerning power density and residence time adjusted in this study. Continuous microwave sterilizer was operated at various masses of oil palm fruit (0.5, 1, 1.5 kg), residence time (6, 8, 10, 12, 14 min), and microwave power (180, 300, 450, 600, 800 W). The resulting temperature in this study ranged from 39 to 97 °C. Observation of the temperature gradient inside-out of a single fruit indicates the interior temperature at the kernel nut is always higher as compared to exterior temperature (abscission layer), with temperature differences ranging from 3 to 23 °C. A minimum power density of 300 W/kg, a residence time of 6 min, and a temperature of 50 °C were required to produce palm oil with FFA less than 5%. Performance indicators of the prototype used in this study are a number of moisture loss dan oil quality. The moisture loss during the sterilization process was around 0.5 to 10.6% which indicates some water content in the fruit, while the content of water, FFA, β-carotene and vitamin E ranging between 1.9 and 17.6%, 0.32-1.74%, 186.14-608.59 ppm and 165.47-610.17 ppm, respectively. © 2001 Elsevier Science. All rights reserved.

The use of oils and fats for frying meals repeatedly causes significant changes in their physical and chemical characteristics. Because of growing health concerns, the assessment of the quality of reused oils has gained a lot of attention, since it is important in identifying the discarding point of the oils. Official analytical procedures employed in laboratories for this purpose need skill, time, and a significant amount of solvent usage. Several rapid test kits based on physical and chemical parameters of oil viz. Fri-Check, Viscofrit, Food oil sensor, Capsens 5000, Food oil monitor, TPM Verifry, Oxifrit, Safetest Peroxide, FFA kit, 3 M oil quality test strips have been developed to simplify oil testing in commercial frying lines, restaurants and food establishment. These test kits typically include a portable apparatus or colorimetric reaction capable of assessing a single parameter directly or indirectly. Besides, the practice of using repeatedly heated oil is very common in food establishments, thence, its essential for rapid assessment of the frying oil quality. This review paper includes the frying concept, health impacts of reusing the frying oil and principle, utility and efficiency of various quality indicators based rapid test kits.

ABSTRACT: When ketosis occurs, supraphysiological levels of free fatty acids (FFA) can cause oxidative injury to the mammary gland and autophagy can regulate the cellular oxidative status. The aim of this study was to investigate the autophagy status of mammary tissue and its associations with oxidative stress in healthy and clinically ketotic dairy cows. Mammary tissue and blood samples were collected from healthy cows [n = 15, β-hydroxybutyrate (BHB) 3.0 mM) at 3 to 15 (average = 7) days in milk. For in vitro study, bovine mammary epithelial cells (BMEC) isolated from healthy cows were treated with 0, 0.3, 0.6, or 1.2 mM FFA for 24 h. Furthermore, BMEC were pretreated with 100 nM rapamycin, an autophagy activator, for 4 h or 50 mM 3-methyladenine (3-MA), an autophagy inhibitor, for 1 h, followed by treatment with or without FFA (1.2 mM) for another 24 h. Oxidation indicators and autophagy-related protein abundance were measured. Compared with healthy cows, serum concentrations of FFA, BHB, and malondialdehyde were greater in clinically ketotic cows, but milk production (kg/d), milk protein (kg/d), activities of superoxide dismutase, catalase, and glutathione peroxidase were lower. Abundances of mRNA and protein of autophagy-related gene 5 (ATG5) and 7 (ATG7) were lower, but sequestosome-1 (SQSTM1, also called p62) greater in mammary tissue of clinically ketotic cows. The mRNA abundance of microtubule-associated protein 1 light chain 3 (MAP1LC3, also called LC3) and protein abundance of LC3-II were lower in mammary tissue of clinically ketotic cows. In vitro, exogenous FFA increased the content of malondialdehyde and reactive oxygen species, but decreased the activities of superoxide dismutase, catalase, and plasma glutathione peroxidase. Compared with the 0 mM FFA group, abundance of ATG5, ATG7, LC3-II was greater, but p62 was lower in the 0.6 mM FFA-treated cells. Similarly, abundance of ATG5, ATG7, and LC3-II was lower, but p62 greater in the 1.2 mM FFA-treated cells relative to 0 mM FFA group. Culture with rapamycin alleviated oxidative stress induced by 1.2 mM FFA, whereas 3-MA aggravated it. Overall, results indicated that a low concentration (0.6 mM) of FFA can induce oxidative stress and activate autophagy in BMEC. At higher concentrations of FFA (1.2 mM), autophagy is impaired and oxidative stress is aggravated. Autophagy is a mechanism for BMEC to counteract FFA-induced stress. As such, it could serve as a potential target for further development of novel strategies against oxidative stress.

Developing an efficient material for the removal of free fatty acids (FFAs) in waste vegetable oil is a challenge in the refining of vegetable oil in food and oleochemical industries. In response to this, N,N(1, 3-phenylene)dimethanimine (NPD) was synthesized via green reaction route without involving solvent. NPD was characterized using Fourier transformed infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), thermogravimetric (TG) analysis, scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). NPD was then applied as a material for the removal of FFA from waste cooking oil (WCO). The synthesis process gave a high yield of 95% of NPD. The FTIR result revealed different functional groups in NPD; the TG showed mass loss at diverse temperature range revealing loss at 80–150, 180–250, 250–410 and 410–600 °C while loss above 600 °C was assigned to loss of char. while TEM revealed the surface of NPD to be smooth with an irregular shape. EDX results further demonstrated the presence of oxygen, nitrogen and carbon in NPD. Removal of FFA from WCO may be described by pseudo-second-order with an adsorption capacity of 42.30 L kg−1. The process obeyed Langmuir isotherm with ∆H of -0.679 kJ mol−1 and ∆S of -0.049 kJ mol−1 K−1 while ∆G increased with increase in temperature. The Density Functional Theory (DFT) concept was used to explain the action of NPD as an adsorbent with the aid of lowest unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital (HOMO). It revealed the mechanism of removal of FFA from WCO by NPD to be via nucleophilic interaction.

Object constancy is one of the most crucial mechanisms of the human visual system enabling viewpoint invariant object recognition. However, the neuronal foundations of object constancy are widely unknown. Research has shown that the ventral visual stream is involved in processing of various kinds of object stimuli and that several regions along the ventral stream are possibly sensitive to the orientation of an object in space. To systematically address the question of viewpoint sensitive object perception, we conducted a study with stroke patients as well as an fMRI experiment with healthy participants applying object stimuli in several spatial orientations, for example in typical and atypical viewing conditions. In the fMRI experiment, we found stronger BOLD signals and above-chance classification accuracies for objects presented in atypical viewing conditions in fusiform face sensitive and lateral occipito-temporal object preferring areas. In the behavioral patient study, we observed that lesions of the right fusiform gyrus were associated with lower performance in object recognition for atypical views. The complementary results from both experiments emphasize the contributions of fusiform and lateral-occipital areas to visual object constancy and indicate that visual object constancy is particularly enabled through increased neuronal activity and specific activation patterns for objects in demanding viewing conditions.

Purpose: Diabetic retinopathy is an increasingly common complication of diabetes mellitus that benefits from early diagnosis and frequent monitoring, especially in pregnancy where there is a greater risk of progression. Fundus fluorescein angiography is currently the gold standard method of investigation for neovascularization. However, this has risks of unpleasant and potentially dangerous side effects, with an added theoretical risk to the fetus in pregnancy. Wide-field optical coherence tomography angiography (PLEX Elite 9000, Carl Zeiss Meditec, Inc. USA and DRI Swept Source OCT Triton, Topcon Medical Systems, Inc. USA) potentially offers a safer, faster and equally effective alternative method for diagnosis and monitoring of diabetic retinopathy in pregnant patients. Observations: In the 3 cases reviewed from our clinic, we found that wide-field optical coherence tomography angiography was successfully used as an alternative to fundus fluorescein angiography in early diagnosis and ongoing monitoring of diabetic retinopathy in pregnant patients. Conclusions and importance: Wide-field optical coherence tomography angiography can be considered as a useful alternative to fundus fluorescein angiography when reviewing pregnant diabetic retinopathy patients. This allows avoidance of any unpleasant and potentially dangerous side effects associated with fluorescein injection, and appears to be just as effective in diagnosis and detecting disease progression.

In the present work, the synthesis of biodiesel has been investigated using low-cost feedstock and a catalyst using conventional and ultrasonic irradiation based approach. The novelty of the present work is used of calcium oxide (CaO) as a catalyst for the synthesis of biodiesel using frying oil as a feedstock via esterification followed by transesterification process. Reaction parameters such as concentration of catalyst, operating temperature, and a molar ratio of oil to methanol (MROM) have been optimized for esterification and transesterification. Reduced free fatty acid value (FFA) helps in the production of pure biodiesel of utmost quality through the transesterification reaction. Decreasing trends of FFA of oil with the increasing temperature, MROM, and catalyst concentration up to the optimized conditions has been obtained during esterification reaction. The maximum reduction in the FFA of oil up to 0.51 mg KOH/g of oil was obtained in 20 min only at an optimal temperature 55°C, MROM of 1:3 and 1 wt. % of H2SO4 during the esterification reaction. The energy required for the conventional based approach was found to be 37.3 kJ/mg. In case of transesterification reaction, it has been observed that the effect of MROM, catalyst concentration, and temperature on yield of biodiesel strongly affects the yield of biodiesel. Decreasing trends of biodiesel yield with increasing range of reaction parameters such as MROM and reaction temperature has been observed for conventional as well as the US irradiation based approach. Furthermore, with increasing heterogeneous CaO catalyst concentration from 0.1 to 0.2 wt. %, yield of biodiesel increases from 72.1 wt. % to 85.7 wt. % and 64.3 wt. % to 68.5 wt. % using a convention-based approach and US-based approach, respectively. The maximum yield of biodiesel as 85.7 wt.% (energy required was 1.8 × 10−4 g/J) was obtained using a conventional based approach and 68.57% (energy required 5.1 × 10−4 g/J) US irradiation based approach at an optimal MROM of 1:8, 0.2 wt. % of CaO and 55°C temperature. Hence, the present study clearly established that significant intensified synthesis of biodiesel can be obtained using optimum MROM, temperature and catalyst concentration via a conventional based approach than the US irradiation based approach.

In this study, the effects of Holothuria tubulosa sea cucumber (Ht- FUC) with different molecular weight (Ht, Ht-1, Ht-2, Ht-3) on β cell apoptosis induced by high-fat-high-sucrose diet (HFD) in male C57BL/6J mice were investigated. After intervention with Ht-FUC (60 mg/kg body weight) for 16 weeks, results showed that different Ht-FUC could significantly decrease blood glucose and insulin levels, and reduce the burden of islet β cell secretion (P

It has been shown that human faces are processed holistically (i.e. as indecomposable wholes, rather than by their component parts) and this holistic face processing is linked to brain activity in face-responsive brain regions. Although several brain regions outside of the face-responsive network are also sensitive to relational processing and perceptual grouping, whether these non-face-responsive regions contribute to holistic processing remains unclear. Here, we investigated holistic face processing in the composite face paradigm both within and outside of face-responsive brain regions. We recorded participants’ brain activity using fMRI while they performed a composite face task. Behavioural results indicate that participants tend to judge the same top face halves as different when they are aligned with different bottom face halves but not when they are misaligned, demonstrating a composite face effect. Neuroimaging results revealed significant differences in responses to aligned and misaligned faces in the lateral occipital complex (LOC), and trends in the anterior part of the fusiform face area (FFA2) and transverse occipital sulcus (TOS), suggesting that these regions are sensitive to holistic versus part-based face processing. Furthermore, the retrosplenial cortex (RSC) and the parahippocampal place area (PPA) showed a pattern of neural activity consistent with a holistic representation of face identity, which also correlated with the strength of the behavioural composite face effect. These results suggest that neural activity in brain regions both within and outside of the face-responsive network contributes to the composite-face effect.

Background: The study aimed to confirm the multimodal imaging of occult macular dystrophy (OMD) with two heterozygous mutations, including an unreported heterozygous EYS mutation., Methods: The study utilised several diagnostic methods, including Optos wide-field imaging, Bruch's membrane opening-minimum rim width (BMO-MRW), optical coherence tomography (OCT), multifocal electroretinogram (mf-ERG), fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and green light autofluorescence (FAF-G) imaging, and genetic testing., Results: The mf-ERG imaging demonstrated decreased P1 amplitudes in both eyes. This was consistent with the FAF-G imaging and OCT results, confirming the bilateral discontinuity of photoreceptors in the macular region. FFA and ICGA revealed persistent macular hypoperfusion not only within the photoreceptors of the macular area but also in the choriocapillaris. Next-generation sequencing results confirmed the presence of two heterozygous mutations in the patient: RP1L1 (c.4273G>C: p. Asp1425His), a hotspot mutation for OMD, and an unreported EYS mutation (c.7382T>A: p. Leu2461Ter) commonly found in retinitis pigmentosa (RP). Analysis using AlphaFold2 further confirmed the impact of the EYS c.7382T>A: p. Leu2461Ter variant on the functional protein conformation., Conclusion: We report an unreported heterozygous EYS mutation that could serve as a promising diagnostic marker for OMD., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024. Published by Elsevier B.V.)

Curvature is one of many visual features shown to be important for visual perception. We recently showed that curvilinear features provide sufficient information for categorizing animate vs. inanimate objects, while rectilinear features do not (Zachariou et al., 2018). Results from our fMRI study in rhesus monkeys (Yue et al., 2014) have shed light on some of the neural substrates underlying curvature processing by revealing a network of visual cortical patches with a curvature response preference. However, it is unknown whether a similar network exists in human visual cortex. Thus, the current study was designed to investigate cortical areas with a preference for curvature in the human brain using fMRI at 7T. Consistent with our monkey fMRI results, we found a network of curvature preferring cortical patches—some of which overlapped well-known face-selective areas. Moreover, principal component analysis (PCA) using all visually-responsive voxels indicated that curvilinear features of visual stimuli were associated with specific retinotopic regions in visual cortex. Regions associated with positive curvilinear PC values encompassed the central visual field representation of early visual areas and the lateral surface of temporal cortex, while those associated with negative curvilinear PC values encompassed the peripheral visual field representation of early visual areas and the medial surface of temporal cortex. Thus, we found that broad areas of curvature preference, which encompassed face-selective areas, were bound by central visual field representations. Our results support the hypothesis that curvilinearity preference interacts with central-peripheral processing biases as primary features underlying the organization of temporal cortex topography in the adult human brain.

Face recognition undergoes prolonged development from childhood to adulthood, thereby raising the question which neural underpinnings are driving this development. Here, we address the development of the neural foundation of the ability to recognize a face across naturally varying images. Fourteen children (ages, 7–10) and 14 adults (ages, 20–23) watched images of either the same or different faces in a functional magnetic resonance imaging adaptation paradigm. The same face was either presented in exact image repetitions or in varying images. Additionally, a subset of participants completed a behavioral task, in which they decided if the face in consecutively presented images belonged to the same person. Results revealed age-related increases in neural sensitivity to face identity in the fusiform face area. Importantly, ventral temporal face-selective regions exhibited more image-invariance – as indicated by stronger adaptation for different images of the same person – in adults compared to children. Crucially, the amount of adaptation to face identity across varying images was correlated with the ability to recognize individual faces in different images. These results suggest that the increase of image-invariance in face-selective regions might be related to the development of face recognition skills.

In this paper a population based evolutionary optimization methodology called firefly algorithm (FFA) is applied for the optimization of system coefficients of the infinite impulse response (IIR) system identification problem. FFA is inspired by the flash pattern and characteristics of fireflies. In FFA technique, behaviour of flashing firefly towards its competent mate is structured. In this algorithm attractiveness depends on brightness of light and a bright firefly feels more attraction for the brighter one. For this optimization problem, brightness varies inversely proportional to the error fitness value, so the position of the brightest firefly gives the optimum result corresponding to the least error fitness in multidimensional search space. Incorporation of different control parameters in basic movement equation results in balancing of exploration and exploitation of search space. The proposed FFA based system identification approach has alleviated from inherent drawbacks of premature convergence and stagnation, unlike genetic algorithm (GA), particle swarm optimization (PSO) and differential evolution (DE). The simulation results obtained for some well known benchmark examples justify the efficacy of the proposed system identification approach using FFA over GA, PSO and DE in terms of convergence speed, identifying plant coefficients and mean square error (MSE) fitness values produced for both same order and reduced order models of adaptive IIR filters.

Background and Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is associated with dyslipidemia and may promote cardiac lipotoxicity. Myocardial free fatty acids (FFA) oxidation (MO FFA ) is normal in pre-diabetes, but reduced in heart failure. We hypothesized that during exercise MO FFA , very low-density lipoprotein triglycerides (VLDL-TG) secretion, hepatic FFA utilization, and lactate production differ among obese subjects with and without MAFLD., Methods: Nine obese subjects with MAFLD and 8 matched subjects without MAFLD (Control) without a history of heart failure and cardiovascular disease were compared before and after 90-min exercise at 50% Peak oxygen consumption. Basal and exercise induced cardiac and hepatic FFA oxidation, uptake and re-esterification and VLDL-TG secretion were measured using [ 11 C]palmitate positron-emission tomography and [1- 14 C]VLDL-TG., Results: In the heart, increased MO FFA was observed after exercise in MAFLD, whereas MO FFA decreased in Control (basal vs exercise, MAFLD: 4.1 (0.8) vs 4.8 (0.8) μmol·100 ml -1  min -1 ; Control: 4.9 (1.8) vs 4.0 (1.1); μmol·100 ml -1  min -1 , mean (SD), p < 0.048). Hepatic FFA fluxes were significantly lower in MAFLD than Control and increased ≈ two-fold in both groups. VLDL-TG secretion was 50% greater in MAFLD at rest and similarly suppressed during exercise. Plasma lactate increased significantly less in MAFLD than Control during exercise., Conclusions: Using robust tracer-techniques we found that obese subjects with MAFLD do not downregulate MO FFA during exercise compared to Control, possibly due to diminished lactate supply. Hepatic FFA fluxes are significantly lower in MAFLD than Control, but increase similarly with exercise. VLDL-TG export remains greater in MAFLD compared to Control. Basal and post-exercise myocardial and hepatic FFA, VLDL-TG and lactate metabolism is abnormal in subjects with MAFLD compared to Control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

A prominent medical application of nanotechnology is represented in drug delivery. In this work, carboxymethyl cellulose (CMC) and poly(vinyl alcohol) (PVA) were used for producing CMC/PVA aqueous-based nanofibers loaded with flufenamic acid (FFA) as a drug containing amine groups. The CMC/PVA solutions with 90/10, 80/20, 70/30, 60/40 and 50/50 ratios were considered for electrospinning. Two integration methods were studied for loading FFA on the nanofibers during the electrospinning process. The characterization techniques of SEM, AFM, fluorescence microscopy and FT-IR spectroscopy were used to study the produced nanofibers, indicating a uniform distribution of FFA throughout the samples. The resulting nanofibers were formed in a diameter range of 176-285 nm and exhibited a 5 h degradation time in the PBS buffer solution. A standard diagram of drug loading was obtained for the samples. The drug release pattern was examined using a dialysis tube method. UV-visible spectroscopy revealed a time-dependent drug release behavior in CMC/PVA/FFA nanofibers where a sharp release occurred over the first 20 min. However, a prolonged release time of 10 h was achieved using a cross-linker (EDC)., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Diabetes-related vascular complication rates remain unacceptably high despite guideline-based medical therapies that are significantly more effective in individuals without diabetes. This critical gap represents an opportunity for researchers and clinicians to collaborate on targeting mechanisms and pathways that specifically contribute to vascular pathology in patients with diabetes mellitus. Dysfunctional mitochondria producing excessive mitochondrial reactive oxygen species (mtROS) play a proximal cell-signaling role in the development of vascular endothelial dysfunction in the setting of diabetes. Targeting the mechanisms of production of mtROS or mtROS themselves represents an attractive method to reduce the prevalence and severity of diabetic vascular disease. This review focuses on the role of mitochondria in the development of diabetic vascular disease and current developments in methods to improve mitochondrial health to improve vascular outcomes in patients with DM., (Copyright © 2018. Published by Elsevier Inc.)

Pathological α-synuclein (α-syn) overexpression and iron (Fe)-induced oxidative stress (OS) are involved in the death of dopaminergic neurons in Parkinson's disease (PD). We have previously characterized the role of triacylglycerol (TAG) formation in the neuronal response to Fe-induced OS. In this work we characterize the role of the α-syn variant A53T during Fe-induced injury and investigate whether lipid metabolism has implications for neuronal fate. To this end, we used the N27 dopaminergic neuronal cell line either untransfected (UT) or stably transfected with pcDNA3 vector (as a transfection control) or pcDNA-A53T-α-syn (A53T α-syn). The overexpression of A53T α-syn triggered an increase in TAG content mainly due to the activation of Acyl-CoA synthetase. Since fatty acid (FA) β-oxidation and phospholipid content did not change in A53T α-syn cells, the unique consequence of the increase in FA-CoA derivatives was their acylation in TAG moieties. Control cells exposed to Fe-induced injury displayed increased OS markers and TAG content. Intriguingly, Fe exposure in A53T α-syn cells promoted a decrease in OS markers accompanied by α-syn aggregation and elevated TAG content. We report here new evidence of a differential role played by A53T α-syn in neuronal lipid metabolism as related to the neuronal response to OS., (Copyright © 2018. Published by Elsevier Inc.)

In obesity, hypertrophic adipocytes secrete high amounts of adipocytokines, resulting in low-grade inflammation amplified by infiltrating proinflammatory macrophages, oxidative stress, hypoxia, and lipolysis. These chronic proinflammatory conditions support the development of type II diabetes and cardiovascular diseases, but the mechanisms of obesity-related exacerbation of inflammatory skin disorders like psoriasis are unclear. In this study, we uncovered dietary saturated fatty acids (SFAs) as major risk factors for the amplification of skin inflammation, independent of obesity-related parameters such as fat mass extension, adipocytokine levels, and glucose homeostasis. Correlation analyses in a cohort of psoriasis vulgaris patients showed that free fatty acid serum level was the only obesity-associated parameter affecting disease severity. Studies in mice with high-fat diet-induced obesity with psoriasiform inflammation confirmed this critical role of free fatty acids. An increase of free fatty acids in healthy, lean mice alone was sufficient to induce an exacerbation of psoriasiform inflammation. In particular, saturated fatty acids sensitize myeloid cells to an increased inflammatory response in answer to proinflammatory stimuli, which in turn augments the activation of keratinocytes. Consequently, reduction of nutritional saturated fatty acids alone diminished the psoriatic phenotype in obese mice. Thus, our findings may open new perspectives for adjuvant dietary measures accompanying anti-inflammatory psoriasis therapies in lean and obese patients., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Face recognition undergoes prolonged development from childhood to adulthood, thereby raising the question which neural underpinnings are driving this development. Here, we address the development of the neural foundation of the ability to recognize a face across naturally varying images. Fourteen children (ages, 7-10) and 14 adults (ages, 20-23) watched images of either the same or different faces in a functional magnetic resonance imaging adaptation paradigm. The same face was either presented in exact image repetitions or in varying images. Additionally, a subset of participants completed a behavioral task, in which they decided if the face in consecutively presented images belonged to the same person. Results revealed age-related increases in neural sensitivity to face identity in the fusiform face area. Importantly, ventral temporal face-selective regions exhibited more image-invariance - as indicated by stronger adaptation for different images of the same person - in adults compared to children. Crucially, the amount of adaptation to face identity across varying images was correlated with the ability to recognize individual faces in different images. These results suggest that the increase of image-invariance in face-selective regions might be related to the development of face recognition skills., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Studies have identified that PKM2 is related to the development of glucose intolerance and insulin resistance in rodents and humans. However, the underlying mechanism remains largely unknown. In the present study, we found that PKM2 expression was significantly elevated in insulin-resistant hepatic tissues and hepatocytes, implicating an association between PKM2 expression and hepatic insulin resistance (IR). In vitro study revealed that overexpression of PKM2 impaired the insulin signaling pathway by decreasing the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3β (GSK3β). Furthermore, PKM2 overexpression enhanced the effects of PA on the lipid accumulation, the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) and hepatic glucose uptake. Intriguingly, PA-induced insulin resistance was suppressed following by the ablation of PKM2 in HepG2 cells. We also found that STAT3 was significantly activated by PKM2 overexpression. Moreover, we identified that PKM2 could interact directly with STAT3. Taken together, these studies demonstrate that PKM2 may promote hepatic IR via STAT3 pathway and would provide a new insight into dissecting the molecular pathogenesis of hepatic insulin resistance., (Copyright © 2017. Published by Elsevier Inc.)

Insulin resistance (IR) is an important determinant of type-2 diabetes mellitus (T2DM). Free fatty acids (FFAs) induce IR by various mechanisms. A surfeit of circulating FFA leads to intra-myocellular lipid accumulation that induces mitochondrial ROS generation and worsens IR. However, the molecular mechanisms behind are unclear. We identified thioredoxin interacting protein (TxNIP), which is overexpressed in T2DM, to be a promoter of ROS-induced IR. We observed upregulation of TxNIP upon palmitate treatment in skeletal muscle cells that led to ROS generation and Glut-4 downregulation resulting in impaired glucose-uptake. FFA-induced overexpression of TxNIP gene was mediated through the activation of its bona-fide trans activator, ChREBP. Further, Palmitate-induced impairment in AMPK-SIRT-1 pathway resulted in overexpression of ChREBP. While Fenofibrate, abrogated PA-induced TxNIP expression and ROS generation in skeletal muscle cells, Saroglitazar, a dual PPARα/γ-agonist, not only inhibited PA-induced TXNIP expression but also led to greater improvement in glucose uptake. Taken together, TxNIP appears to be an important factor in FFA-induced ROS generation and IR in skeletal muscle cells, which can be modulated for the management of this complex disorder., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD), frequently associated with obesity and diabetes mellitus, is caused by the accumulation of excess fatty acids within liver cells. Palmitic acid (PA), a common saturated fatty acid found in mammals, induces the generation of reactive oxygen species (ROS) and elicits apoptotic cell death, known as lipotoxicity. However, protective mechanisms against PA-induced lipotoxicity have not been elucidated. In this study, we aimed to clarify the role of p62, an adapter protein in the autophagic process, as well as the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway, in protecting cells from PA-induced lipotoxicity. The Nrf2-Keap1 pathway is essential for the protection of cells from oxidative stress. p62 enhances its binding to Keap1 and leads to Nrf2 activation. Here, we show that PA potentiates Keap1 degradation and thereby activates the transcription of Nrf2 target genes partially through autophagy. Furthermore, this PA-mediated Keap1 degradation depends on p62. Correspondingly, a lack of p62 attenuates the PA-mediated Nrf2 activation and increases the susceptibility of cells to oxidative stress. These results indicate that p62 plays an important role in protecting cells against lipotoxicity through Keap1 degradation-mediated Nrf2 activation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Non-shivering thermogenesis in brown adipose tissue (BAT) plays a central role in energy homeostasis. Thioesterase superfamily member 1 (Them1), a BAT-enriched long chain fatty acyl-CoA thioesterase, is upregulated by cold and downregulated by warm ambient temperatures. Them1−/− mice exhibit increased energy expenditure and resistance to diet-induced obesity and diabetes, but the mechanistic contribution of Them1 to the regulation of cold thermogenesis remains unknown. Methods: Them1−/− and Them1+/+ mice were subjected to continuous metabolic monitoring to quantify the effects of ambient temperatures ranging from thermoneutrality (30 °C) to cold (4 °C) on energy expenditure, core body temperature, physical activity and food intake. The effects of Them1 expression on O2 consumption rates, thermogenic gene expression and lipolytic protein activation were determined ex vivo in BAT and in primary brown adipocytes. Results: Them1 suppressed thermogenesis in mice even in the setting of ongoing cold exposure. Without affecting thermogenic gene transcription, Them1 reduced O2 consumption rates in both isolated BAT and primary brown adipocytes. This was attributable to decreased mitochondrial oxidation of endogenous but not exogenous fatty acids. Conclusions: These results show that Them1 may act as a break on uncontrolled heat production and limit the extent of energy expenditure. Pharmacologic inhibition of Them1 could provide a targeted strategy for the management of metabolic disorders via activation of brown fat.

Functional areas specialized for recognition can be activated by a non-preferred stimulus as well as a preferred stimulus. The functional magnetic resonance imaging signals detected in response to different stimuli in an area may have the same or different amplitudes. However, it is uncertain whether the responses originate from the same neuronal populations or heterogeneous ones. To address this concern, we propose a novel method that uses multi-echo echo-planar imaging sequences to evaluate changes in the transverse relaxation profile caused by stimulation. According to this method, the areas related with visual recognition, i.e. fusiform face area and parahippocampal place area, have different transverse relaxation profiles to preferred and non-preferred stimuli, which can be considered as reflecting a difference in neuronal population processing stimuli in those areas. The proposed method can be useful for probing the microscopic functional specificity of brain areas., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Although physical properties of neonatal-infantile stratum corneum (SC) change drastically after birth, precise developmental alterations of specific sites have not been fully elucidated., Objective: To determine the longitudinal alterations of neonatal-infantile SC functions and components of upper thighs and diaper-covered buttocks during the first year of life. The data were compared with those of adults., Methods: Nineteen full-term neonates and their mothers were subjected to the measurements. Skin hydration, water sorption/retention capacity, TEWL were measured. Superficial SC analyses for NMF, ester binding sebum, and free fatty acids were performed by ATR-FTIR spectrometer. Total amount of ceramides (CERs) and CER subclasses were analyzed by NPLC-ESI-MS., Results: SC hydration of neonatal thighs was lower than that of their mothers, which rapidly increased during the 1st month. Skin hydration of neonatal buttocks was similar to that of their mothers. This also rapidly increased during the 1st month. The neonatal TEWL was less than those of their mothers indicating more efficient barrier function at both sites, which significantly increased during the 1st year development. This was mostly correlated decreased in the ω-hydroxy fatty acid-esterified CERs. Superficial ester-binding sebum content of neonates was similar to that of their mothers, which significantly decreased during the measurement; the decrease was more marked on buttocks. Neither NMF nor FFA of the superficial SC showed significant alteration during the 1-year development., Conclusion: Our results indicate that physical functions and components of neonatal-infantile SC show considerable alterations between diaper-covered buttocks and upper thighs during the 1st year development., (Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background & Aims: A common cause of liver donor ineligibility is macrosteatosis. Recovery of such livers could enhance donor availability. Living donor studies have shown diet-induced reduction of macrosteatosis enables transplantation. However, cadaveric liver macrosteatotic reduction must be performed ex vivo within hours. Towards this goal, we investigated the effect of accelerated macrosteatosis reduction on hepatocyte viability and function using a novel system of macrosteatotic hepatocytes., Methods: Hepatocytes isolated from lean Zucker rats were cultured in a collagen sandwich, incubated for 6 days in fatty acid-supplemented medium to induce steatosis, and then switched for 2 days to medium supplemented with lipid metabolism promoting agents. Intracellular lipid droplet size distribution and triglyceride, viability, albumin and urea secretion, and bile canalicular function were measured., Results: Fatty acid-supplemented medium induced microsteatosis in 3 days and macrosteatosis in 6 days, the latter evidenced by large lipid droplets dislocating the nucleus to the cell periphery. Macrosteatosis significantly impaired all functions tested. Macrosteatosis decreased upon returning hepatocytes to standard medium, and the rate of decrease was 4-fold faster with supplemented agents, yielding 80% reduction in 2 days. Viability of macrosteatosis reduced hepatocytes was similar to control lean cells. Accelerated macrosteatotic reduction led to faster recovery of urea secretion and bile canalicular function, but not of albumin secretion., Conclusions: Macrosteatosis reversibly decreases hepatocyte function and supplementary agents accelerate macrosteatosis reduction and some functional restoration with no effect on viability. This in vitro model may be useful to screen agents for macrosteatotic reduction in livers before transplantation., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Ceramide hydrolysis by ceramidase in the stratum corneum (SC) yields both sphingoid bases and free fatty acids (FFA). While FFA are key constituents of the lamellar bilayers that mediate the epidermal permeability barrier, whether sphingoid bases influence permeability barrier homeostasis remains unknown. Pertinently, alterations of lipid profile, including ceramide and ceramidase activities occur in atopic dermatitis (AD)., Object: We investigated alterations in sphingoid base levels and/or profiles (sphingosine to sphinganine ratio) in the SC of normal vs. AD mice, a model that faithfully replicates human AD, and then whether altered sphingoid base levels and/or profiles influence(s) membrane stability and/or structures., Methods: Unilamellar vesicles (LV), incorporating the three major SC lipids (ceramides/FFA/cholesterol) and different ratios of sphingosine/sphinganine, encapsulating carboxyfluorescein, were used as the model of SC lipids. Membrane stability was measured as release of carboxyfluorescein. Thermal analysis of LV was conducted by differential scanning calorimetry (DSC)., Results: LV containing AD levels of sphingosine/sphinganine (AD-LV) displayed altered membrane permeability vs. normal-LV. DSC analyses revealed decreases in orthorhombic structures that form tightly packed lamellar structures in AD-LV., Conclusion: Sphingoid base composition influences lamellar membrane architecture in SC, suggesting that altered sphingoid base profiles could contribute to the barrier abnormality in AD., (Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: Lipoprotein lipase (LPL) is a key regulator of circulating triglyceride rich lipoprotein hydrolysis. In brain LPL regulates appetite and energy expenditure. Angiopoietin-like 4 (Angptl4) is a secreted protein that inhibits LPL activity and, thereby, triglyceride metabolism, but the impact of Angptl4 on central lipid metabolism is unknown. Methods: We induced type 1 diabetes by streptozotocin (STZ) in whole-body Angptl4 knockout mice (Angptl4-/-) and their wildtype littermates to study the role of Angptl4 in central lipid metabolism. Results: In type 1 (streptozotocin, STZ) and type 2 (ob/ob) diabetic mice, there is a ~2-fold increase of Angptl4 in the hypothalamus and skeletal muscle. Intracerebroventricular insulin injection into STZ mice at levels which have no effect on plasma glucose restores Angptl4 expression in hypothalamus. Isolation of cells from the brain reveals that Angptl4 is produced in glia, whereas LPL is present in both glia and neurons. Consistent with the in vivo experiment, in vitro insulin treatment of glial cells causes a 50% reduction of Angptl4 and significantly increases LPL activity with no change in LPL expression. In Angptl4-/- mice, LPL activity in skeletal muscle is increased 3-fold, and this is further increased by STZ-induced diabetes. By contrast, Angptl4-/- mice show no significant difference in LPL activity in hypothalamus or brain independent of diabetic and nutritional status. Conclusion: Thus, Angptl4 in brain is produced in glia and regulated by insulin. However, in contrast to the periphery, central Angptl4 does not regulate LPL activity, but appears to participate in the metabolic crosstalk between glia and neurons.

Background: Saturated free fatty acids (FFAs), such as palmitate, cause β-cell apoptosis whereas unsaturated FFAs, e.g. oleate, are not harmful. The toxicity of palmitate could be mediated through endoplasmic reticulum (ER) stress which triggers the activation of a signal responding cascade also called unfolded protein response (UPR). We investigated whether or not palmitate induced β-cell apoptosis through UPR activation and whether or not oleate as a monounsaturated fatty acid could counteract these effects., Methods: INS-1E β-cells were incubated with palmitate [0.5mM], oleate [1mM] or the combination [0.5/1mM] for 1, 6 and 24h. Viability and induction of apoptosis were measured by WST-1 assay and FITC-Annexin/PI-staining, respectively. Western blot analyses were performed for UPR specific proteins and mRNA expression of target molecules was determined by qPCR., Results: Palmitate significantly decreased viability (29±8.8%) of INS-1E β-cells compared to controls after 24h. Stimulation with oleate showed no effect on viability but the combination of oleate and palmitate improved viability compared to palmitate treated cells (55±9.3%) or controls (26±5.3%). The number of apoptotic cells was increased 2-fold after 24h incubation with palmitate compared to controls. Again, oleate showed no effect but in combination ameliorated the effect of palmitate to control level. Phosphorylation of eIF2α was increased after 6 and 24h incubation with palmitate. In contrast, oleate had no effect and in combination prevented phosphorylation of eIF2α. Increased Xbp1 splicing was visible already 6h after palmitate treatment and remained elevated at 24h. The combination with oleate abolished Xbp1 splicing. Interestingly, mRNA expression of the chaperones Bip, Pdi, Calnexin and Grp94 was not altered by FFA treatment. Only the proapoptotic transcription factor Chop was significantly enhanced by palmitate incubation. In accordance with sustained cell survival the combination as well as oleate alone, did not result in increased Chop levels compared to controls. In summary, we showed that oleate protects INS-1E β-cells from palmitate-induced apoptosis by the suppression of ER stress which was independent of chaperone activation., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

Given that the variation in how regional adipose tissue handles and stores excess dietary energy has substantial cardiometabolic implications, ectopic fat distribution might be an important predictor of cardiometabolic and vascular risk, in addition to overall obesity itself. Conceptually, ectopic fat depots may be divided into systemically acting fat depots and locally acting fat depots. Systemically acting fat depots include visceral fat, fat in the liver, muscle, or neck, and subcutaneous fat. Accumulation in the abdominal visceral area, compared with overall obesity, has an equally or more important role in the development of cardiometabolic risk. Fat depots in liver/muscle tissue cause adverse cardiometabolic effects by affecting energy metabolism. Fat depots in lower-body subcutaneous areas may be protective regarding cardiometabolic risk, by trapping remnant energy. Fat accumulation in the neck is a unique type of fat depot that may increase cardiovascular risk by increasing insulin resistance. Locally acting fat depots include pericardial fat, perivascular fat, and renal sinus fat. These fat depots have effects primarily on adjacent anatomic organs, directly via lipotoxicity and indirectly via cytokine secretion. Pericardial fat is associated with coronary atherosclerosis. Perivascular fat may play an independent role in adverse vascular biology, including arterial stiffness. Renal sinus fat is a unique fat depot that may confer additional cardiometabolic risk. Thus, ectopic fat depots may contribute to the understanding of the link between body composition and cardiometabolic risk. In this review, we focus on the role and clinical implications of ectopic fat depots in cardiometabolic and vascular risk., (© 2013.)

The blood free fatty acids (FFAs), which provide energy to the cell and act as substrates in the synthesis of fats, lipoproteins, liposaccharides, and eicosanoids, involve in a number of important physiological processes. In the present study, matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS) with ammonia-treated N-(1-naphthyl) ethylenediamine dihydrochloride (ATNEDC) as a novel MALDI matrix in a negative ion mode was employed to directly quantify serum FFAs. Multiple point internal standard calibration curves between the concentration ratios of individual fatty acids to internal standard (IS, C17:0) versus their corresponding intensity ratios were constructed for C14:0, C16:1, C16:0, C18:0, C18:1, C18:2, C18:3, C20:4, and C22:6, respectively, in their mixture, with correlation coefficients between 0.991 and 0.999 and limits of detection (LODs) between 0.2 and 5.4μM, along with the linear dynamic range of more than two orders of magnitude. The results indicate that the multiple point internal standard calibration could reduce the impact of ion suppression and improve quantification accuracy in the MALDI mode. The quantitative results of nine FFAs from 339 serum samples, including 161 healthy controls, 118 patients with hyperglycemia and 60 patients without hyperglycemia show that FFAs levels in hyperglycemic patient sera are significantly higher than those in healthy controls and patients without hyperglycemia, and elevated FFA levels are also associated with increased levels of fasting blood glucose (FBG) in hyperglycemic patient sera. Serum FFAs were identified on the basis of the observed accurate molecular masses and reliable isotope distributions obtained by MALDI-FTICR MS., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Pigment epithelium-derived factor is well known as a secreted glycoprotein with multiple functions, such as anti-angiogenic, neuroprotective and anti-tumor activities. However, its intracellular role remains unknown. The present study was performed to demonstrate the intracellular function of pigment epithelium-derived factor on triglyceride degradation. Hepatic pigment epithelium-derived factor levels increased at the early stage and subsequently decreased after 16 weeks in high-fat-diet-fed mice compared to those in chow-fed mice. Similarly, oleic acid led to long-term downregulation of pigment epithelium-derived factor in HepG2 cells. Endogenous pigment epithelium-derived factor was an intracellular protein with cytoplasmic distribution in hepatocytes by immunostaining. Exogenous FITC-labeled pigment epithelium-derived factor could be absorbed into hepatocytes. Both signal peptide deletion and full-length pigment epithelium-derived factor transfection HeLa cells and hepatocytes promoted triglyceride degradation. Intracellular pigment epithelium-derived factor co-immunoprecipitated with adipose triglyceride lipase and promoted triglyceride degradation in an adipose triglyceride lipase-dependent manner. Additionally, pigment epithelium-derived factor bound to the C-terminal of adipose triglyceride lipase (aa268-504) and adipose triglyceride lipase-G0/G1 switch gene-2 complex simultaneously, which facilitated adipose triglyceride lipase-G0/G1 switch gene-2 translocation onto lipid droplet using bimolecular fluorescence complementation assay. Moreover, knockdown of endogenous pigment epithelium-derived factor in hepatocytes diminished triglyceride degradation. Taken together, these results indicate that hepatic pigment epithelium-derived factor was decreased in obese mice accompanied with hepatic steatosis. Intracellular pigment epithelium-derived factor binds to and facilitates adipose triglyceride lipase translocation onto lipid droplet, which promotes triglyceride degradation. These findings suggest that a decreased level of hepatic pigment epithelium-derived factor may contribute to hepatic steatosis in obesity., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Inflammation can be either beneficial or detrimental to the liver, depending on multiple factors. Mild (i.e., limited in intensity and destined to resolve) inflammatory responses have indeed been shown to exert consistent hepatoprotective effects, contributing to tissue repair and promoting the re-establishment of homeostasis. Conversely, excessive (i.e., disproportionate in intensity and permanent) inflammation may induce a massive loss of hepatocytes and hence exacerbate the severity of various hepatic conditions, including ischemia-reperfusion injury, systemic metabolic alterations (e.g., obesity, diabetes, non-alcoholic fatty liver disorders), alcoholic hepatitis, intoxication by xenobiotics and infection, de facto being associated with irreversible liver damage, fibrosis, and carcinogenesis. Both liver-resident cells (e.g., Kupffer cells, hepatic stellate cells, sinusoidal endothelial cells) and cells that are recruited in response to injury (e.g., monocytes, macrophages, dendritic cells, natural killer cells) emit pro-inflammatory signals including - but not limited to - cytokines, chemokines, lipid messengers, and reactive oxygen species that contribute to the apoptotic or necrotic demise of hepatocytes. In turn, dying hepatocytes release damage-associated molecular patterns that-upon binding to evolutionary conserved pattern recognition receptors-activate cells of the innate immune system to further stimulate inflammatory responses, hence establishing a highly hepatotoxic feedforward cycle of inflammation and cell death. In this review, we discuss the cellular and molecular mechanisms that account for the most deleterious effect of hepatic inflammation at the cellular level, that is, the initiation of a massive cell death response among hepatocytes., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Ectotherm animals including insects are known to undergo seasonal restructuring of the cell membranes in order to keep their functionality and/or protect their structural integrity at low body temperatures. Studies on insects so far focused either on fatty acids or on composition of molecular species in major phospholipid classes. Here we extend the scope of analysis and bring results on seasonal changes in minor phospholipid classes, lysophospholipids (LPLs), free fatty acids, phytosterols and tocopherols in heteropteran insect, Pyrrhocoris apterus. We found that muscle tissue contains unusually high amounts of LPLs. Muscle and fat body tissues also contain high amounts of β-sitosterol and campesterol, two phytosterols derived from plant food, while only small amounts of cholesterol are present. In addition, two isomers (γ and δ) of tocopherol (vitamin E) are present in quantities comparable to, or even higher than phytosterols in both tissues. Distinct seasonal patterns of sterol and tocopherol concentrations were observed showing a minimum in reproductively active bugs in summer and a maximum in diapausing, cold-acclimated bugs in winter. Possible adaptive meanings of such changes are discussed including: preventing the unregulated transition of membrane lipids from functional liquid crystalline phase to non-functional gel phase; decreasing the rates of ion/solute leakage; silencing the activities of membrane bound enzymes and receptors; and counteracting the higher risk of oxidative damage to PUFA in winter membranes., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background & Aims: Circulating insulin-like growth factor-1 (IGF-1) plays a pivotal role in mediating the aging process. This study was designed to evaluate the effect of liver IGF-1 deficiency (LID) on aging-induced changes in hepatic function and underlying mechanisms, with a focus on autophagy., Methods: Plasma and liver samples were obtained from young (3-mo) and aged (24-mo) wild type (WT) and LID mice. Levels of AST, ALT, triglyceride, hepatic lipofuscin, steatosis, fibrosis, and nuclear morphology were analyzed. Western blot was employed to evaluate autophagy. Human HepG2 cells were treated with free fatty acid (FFA) to mimic hepatic aging in the absence or presence of IGF-1 siRNA. SA-β-gal activity was detected using flow cytometry and a fluorescence microplate reader. GFP-LC3 was used to assess autophagy activity in HepG2 cells., Results: Median survival was longer in LID mice compared with WT mice. Aging was associated with elevated levels of triglyceride, AST and ALT, lipofuscin accumulation, steatosis, fibrosis and nuclear injury, which were significantly attenuated by liver IGF-1 deficiency. Levels of autophagy were suppressed in senescent livers, the effect was reversed in the liver of IGF-1 deficient mice. In HepG2 cells, FFA induced the accumulation of β-gal, which was dramatically suppressed by IGF-1 knockdown. Importantly, inhibiting autophagy using 3-methyladenine mitigated IGF-1 knockdown-induced preservation of autophagic vacuole formation and inhibition of β-gal accumulation in the presence of FFA in HepG2 cells., Conclusions: Our data revealed that IGF-1 deficiency ameliorated aging-induced hepatic injury, possibly through preventing a concomitant diminution in autophagy. These data provide new insight into the role of IGF-1 and autophagy in the management of aging-induced hepatic injury., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)