Elevated Saturated Fatty Acids Research Articles

Comparative Analysis of Fatty Acids Concentration in Liver and Muscle Tissues of Rats and Mice

This study conducted a comparative analysis of fatty acids (FAs) concentration derived from polar (PL) and non-polar (NPL) lipids in the liver and muscle tissues of rats and mice. The objective was to elucidate species-specific differences in tissue FA distribution. Employing targeted GC/MS-based methodology, the study aimed to provide insights into conserved and species-specific aspects of lipid metabolism, thereby enhancing future experimental design, linked with comprehension of the interactions between diet, metabolism, and health. Results revealed markedly higher levels of total fatty acids (TFAs) derived from PL in mice skeletal muscle compared to rats and elevated saturated fatty acids (SFAs) levels in mice. Unsaturated fatty acid levels, mainly monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs), were substantially higher in mice muscle across all lipid classes, resulting in a higher PUFA/TFA ratio in mice muscle. Detailed analysis of specific unsaturated fatty acids (C16:1, C18:1n9c, C18:2n6c, C22:6n3) indicated elevated levels in mice relative to rats. Conversely, rats exhibited higher SFA levels derived from the NPL fraction in the liver, particularly in myristic (C14:0), stearic (C18:0), and tricosanoic (C23:0) acids. Mice liver PL fractions displayed significantly elevated unsaturated FA levels, with notably higher MUFAs and lower PUFAs in NPL fractions compared to rats. Analysis of specific unsaturated FAs revealed higher levels of palmitoleic acid (C16:1) in mice, while rats exhibited increased linoleic (C18:2n6c) and linolenic (C18:3n3) acids. In conclusion, significant differences in FAs tissue distribution between rats and mice underscore the importance of considering species-specific FAs variations when utilizing these animal models and interpreting experimental results related to FA metabolism.

Associations between Serum Saturated Fatty Acids Content and Mortality in Dialysis Patients.

Background: Cardiovascular mortality in dialysis population remains very high. Saturated fatty acids (SFA) contribute to atherosclerosis and to cardiovascular risk. Aim: The aim of this study was to evaluate the relationship between mortality in dialysis patients and the serum SFA content. Methods: Survival of 54 patients on dialysis was assessed. A total of 21 SFA from patients’ sera were measured by gas chromatography-mass spectrometry (GC-MS). Diet was assessed by food frequency questionnaire FFQ-6. The SFA content is presented as fatty acid proportion (%). Results: During the observation time (median 66 months) 22 patients died. There was a significant relationship between elevated SFA (above SFA mean) and mortality (log-rank 3.13; p = 0.0017). Moreover, patients who ingested foods rich in SFA, according to FFQ-6, had a higher mortality risk (log-rank 2.24; p = 0.03). The hazard ratio for mortality associated with increased SFA content equalled 4.47 (1.63–12.26). Addition of age and inflammation (hsCRP > 5 mg/L) into the Cox model did not modify this relationship. However, SFA content turned out to be significantly higher in patients with diabetes mellitus and cardiovascular disease, as compared to patients free from these co-morbidities. Their addition to the model attenuated the relationship between SFA and mortality, making it statistically insignificant. Conclusion: The serum content of SFA turned out to be a strong predictor of mortality in dialysis patients. However, given the significant associations between SFA, DM, and CVD, interventional studies with controlled SFA intake are needed to evaluate the causal links between SFA, co-morbidities and survival.

Regional, seasonal and age class blubber fatty acid signature analysis of harbour seals in Alaska from 1997 to 2010.

Alaskan harbour seal populations are currently listed as a species of special concern. Although there is evidence of recent stabilization or even partial recovery of harbour seal numbers in areas of historic decline, most populations have not made substantial recoveries. To date, few data exist regarding spatial and seasonal changes in blubber fatty acids (FAs) for Alaskan harbour seal populations. The purpose of this study was to qualitatively investigate harbour seal blubber FA profiles for regional, seasonal and age class differences. Blubber FA concentrations were analysed using MANOVA and linear discriminant analysis (LDA) from 760 individual harbour seals across Bristol Bay, Kodiak, Prince William Sound and Southeast Alaska from 1997 to 2010. Our results suggest spatial and seasonal differences are largely driven by monounsaturated FAs, most notably 14:1n-5, 16:1n-7 and 18:1n-7. In addition, our data revealed a progression in blubber FAs from pups to adults, with a shift from saturated FAs and short-chained monounsaturated FAs in the pup blubber to more long-chain monounsaturated FAs and polyunsaturated FAs in adults. Lastly, harbour seals pups had elevated saturated FA 16:0 concentrations when compared to other age classes, regardless of location or period. With this vast spatial and seasonal FA information, we believe future sampling of blubber FAs from Alaskan harbour seal populations could be a useful tool in assessing the response of this species and its ecosystem to changes associated with natural and anthropogenic pressures.

Upregulation of SLAMF3 on human T cells is induced by palmitic acid through the STAT5-PI3K/Akt pathway and features the chronic inflammatory profiles of type 2 diabetes

Metabolic stress-induced low-grade chronic inflammation plays an important role in the development of insulin-resistance and type 2 diabetes (T2D). Emerging evidence highlights the importance of directly elucidating T-cell activation under the obesity-induced metabolic stress condition, as T cells primed under such conditions were found to acquire a unique phenotype and function. Herein, we found a significant upregulation of signaling lymphocytic activation molecule family member 3 (SLAMF3) expression on T cells from T2D patients compared to those of healthy controls. Importantly, SLAMF3 upregulation was associated with an increased ability to produce proinflammatory cytokines. Significantly increased SLAMF3 expression was seen in T2D patient T cells that produce IFN-γ or IL-17 upon short (4-h) stimulation, compared to non-cytokine-producing T cells. In line with this finding, SLAMF3high T cells were significantly more sensitive than SLAMF3low T cells to TCR stimulation with anti-CD3/CD28 antibodies. Furthermore, treatment with palmitic acid (PA) led to significant upregulation of SLAMF3 on human T cells primed by anti-CD3/CD28 antibodies and on Jurkat cells, a human T-cell line. RNA sequencing revealed strong activation of the PI3K/Akt signaling pathway in T cells that were primed with PA. Further mechanistic studies showed that inhibition of PI3K/Akt signaling, or its upstream mediator STAT5 can prevent PA-induced SLAMF3 upregulation on T cells. These results indicate that SLAMF3 upregulation is associated with T-cell activation and cytokine production in T2D patients, and suggest that elevated saturated fatty acids in T2D patients may induce SLAMF3 upregulation on T cells via activation of the STAT5-PI3K/Akt signaling pathway.

Palmitic acid causes insulin resistance in granulosa cells via activation of JNK.

Obesity is a worldwide health problem with rising incidence and results in reproductive difficulties. Elevated saturated free fatty acids (FFAs) in obesity can cause insulin resistance (IR) in peripheral tissues. The high intra-follicular saturated FFAs may also account for IR in ovarian granulosa cells (GCs). In the present study, we investigated the relationship between saturated FFAs and IR in GCs by the use of palmitic acid (PA). We demonstrated that the glucose uptake in cultured GCs and lactate accumulation in the culture medium were stimulated by insulin, but the effects of insulin were attenuated by PA treatment. Besides, insulin-induced phosphorylation of Akt was reduced by PA in a dose- and time-dependent manner. Furthermore, PA increased phosphorylation of JNK and JNK blockage rescued the phosphorylation of Akt which was downregulated by PA. These findings highlighted the negative effect of PA on GCs metabolism and may partially account for the obesity-related reproductive disorders.

Upregulation of SLAMF3 on Human T cells Is Induced by Palmitic Acid Through the STAT5-PI3K/Akt Pathway and Features the Chronic Inflammatory Profiles of Type 2 Diabetes

Background: Metabolic stress-induced low-grade chronic inflammation plays an important role in the development of insulin-resistance and type 2 diabetes (T2D). Emerging evidence highlights the importance of directly elucidating T cell activation under the obesity-induced metabolic stress condition and the underline mechanisms, which remain elusive. Methods: T cells from T2D patients and health controls were analyzed for activation and cytokine production by flow cytometry. The effect of palmitic acid on T cells was assessed by in vitro assays. RNA sequencing and inhibitor blocking assays were used to determine the signaling pathways involved in palmitic acid-induced SLAMF3 upregulation on T cells. Findings: We found a significant upregulation of SLAMF3, a molecule regulates immune function through homophilic interactions, on T cells from T2D patients compared to those of healthy controls. Importantly, SLAMF3 upregulation was associated with an increased ability to produce proinflammatory cytokines including IFN-γ and IL-17. Additionally, SLAMF3high T cells were significantly more sensitive than SLAMF3low T cells to TCR stimulation with anti-CD3/CD28 antibodies. Palmitic acid was found to cause significant upregulation of SLAMF3 on primary human T cells as well as Jurkat cells. Further mechanistic studies showed that inhibition of PI3K/Akt signaling, or its upstream mediator STAT5 can prevent palmitic acid-induced SLAMF3 upregulation on T cells. Interpretation: These results indicate that SLAMF3 upregulation is associated with T cell activation and cytokine production in T2D patients, and suggest that elevated saturated fatty acids in T2D patients may induce SLAMF3 upregulation on T cells via activation of the STAT5-PI3K/Akt signaling pathway. Funding Statement: This work was supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030303), Chinese MOST (2015CB964400 and 2017YFA0104402), NSFC (81570145, 81870091, 91642208, 91742107, and 81501279), Plan B for Bethune Project of Jilin University (2015210), an innovation capability project of Jilin Province Development and Reform Commission (2017C019), an open topic of Jilin Province Science and Technology Agency (20170623092TC-01 & 20180623083TC-01). Declaration of Interests: The author(s) declare no competing financial interests. Ethics Approval Statement: Protocols involved in the use of human samples were approved by the Institutional Review Board, and all of the experiments were performed in accordance with the protocols.

A central-acting connexin inhibitor, INI-0602, prevents high-fat diet-induced feeding pattern disturbances and obesity in mice

A high-fat diet (HFD) causes obesity by promoting excessive energy intake, and simultaneously, by disturbing the timing of energy intake. Restoring the feeding pattern is sufficient to prevent HFD-induced obesity in mice. However, the molecular mechanism(s) underlying HFD-induced feeding pattern disturbances remain elusive. Saturated fatty acids activate microglia and cause hypothalamic inflammation. Activated microglia cause neuroinflammation, which spreads via inflammatory cytokines and gap-junction hemichannels. However, the role of gap-junction hemichannels in HFD-induced obesity remains unaddressed. We used a novel, central-acting connexin inhibitor, INI-0602, which has high affinity for gap junction hemichannels and does not affect the induction of inflammatory cytokines. We analyzed ad libitum feeding behavior and locomotor activity in mice that were fed normal chow (NC), a HFD with elevated saturated fatty acids (SFAs), or a HFD with very high SFAs. We found that HFD feeding induced acute hyperphagia, mainly during the light cycle. Feeding pattern disturbances were more pronounced in mice that consumed the HFD with very high SFAs than in mice that consumed the HFD with elevated SFAs. When INI-0602 was administered before the HFD was introduced, it blocked the feeding pattern disturbance, but not locomotor activity disturbances; moreover, it prevented subsequent diet-induced obesity. However, when INI-0602 was administered after the HFD had disturbed the feeding pattern, it failed to restore the normal feeding pattern. Therefore, we propose that SFAs in HFDs played a major role in disrupting feeding patterns in mice. Moreover, the feeding pattern disturbance required the function of central, gap junction hemichannels at the initiation of a HFD. However, altering hemichannel function after the feeding pattern disturbance was established had no effect. Thus, preventing the occurrence of a feeding pattern disturbance by blocking the hemichannel pathway was associated with the prevention of the HFD-induced obesity in mice.

Palmitic acid-induced neuron cell cycle G2/M arrest and endoplasmic reticular stress through protein palmitoylation in SH-SY5Y human neuroblastoma cells.

Obesity-related neurodegenerative diseases are associated with elevated saturated fatty acids (SFAs) in the brain. An increase in SFAs, especially palmitic acid (PA), triggers neuron cell apoptosis, causing cognitive function to deteriorate. In the present study, we focused on the specific mechanism by which PA triggers SH-SY5Y neuron cell apoptosis. We found that PA induces significant neuron cell cycle arrest in the G2/M phase in SH-SY5Y cells. Our data further showed that G2/M arrest is involved in elevation of endoplasmic reticular (ER) stress according to an increase in p-eukaryotic translation inhibition factor 2α, an ER stress marker. Chronic exposure to PA also accelerates beta-amyloid accumulation, a pathological characteristic of Alzheimer’s disease. Interestingly, SFA-induced ER stress, G2/M arrest and cell apoptosis were reversed by treatment with 2-bromopalmitate, a protein palmitoylation inhibitor. These findings suggest that protein palmitoylation plays a crucial role in SFA-induced neuron cell cycle G2/M arrest, ER stress and apoptosis; this provides a novel strategy for preventing SFA-induced neuron cell dysfunction.

Perspectives and Research Challenges in Veterinary Infectious Diseases

Technical breakthroughs have highlighted the host–microbe interactome to explore the immune system and the role for microorganisms in the development and function of the immune system. While these interaction studies have provided a window on the pathogenesis of the disease, there is a distinct lack of information on the effect of these interactions in the overall host physiology. For example, the seminal work conducted in human medicine demonstrating that subclinical inflammation has dramatic effects on host physiology resulting in diseases such as obesity, type 2 diabetes, and cardiovascular disease. This is an area of interest for this journal. What effects do subclinical infections have on the pathophysiology of animals resulting in what is believed to be acceptable production losses, but may actually be preventable? The immune response and nutrient metabolism are two fundamental biological systems indispensable to maintaining and preserving life. Each of these systems is capable of modulating the activity of the other to ensure that the host animal is capable of coordinating the appropriate responses under any conditions. Thus, metabolic systems are integrated with pathogen-sensing and immune responses, and these pathways are evolutionarily conserved. Yet, we know very little about the effect of infections on host metabolism. Several important networks sense and manage nutrients and integrate with immune and inflammatory pathways to influence the physiological and pathological metabolic states. For example, the Toll-like receptors (TLRs), a family of the innate sensors, recognize specific microbial components, but can also sense nutritional signals, such as elevated glucose levels and saturated fatty acids. Likewise, metabolism-signaling pathways, such as leptin and other hormones, can also regulate immune functions. Thus, any immune alteration, specifically inflammation, can cause disturbances in host metabolism. New insights into infectious disease pathogenesis and animal production that can result in the discovery of novel diagnostic approaches and/or therapeutics are of high priority for the journal. The Veterinary Infectious Disease specialty section seeks to become an outlet for veterinary research into infectious diseases through the study of the pathogen or its host or of the host’s environment, or by addressing combinations of these aspects of the disease system. We vision research in this area will exploit the very latest technologies to improve our understanding of the host–pathogen interface or its relationship with the host animal’s environment. With this in mind, we see the following areas of research that present needs and challenges in the immediate future.

Epigenetic Regulation of Macrophage Polarization by DNA Methyltransferase 3b

Adipose tissue macrophages (ATMs) undergo a phenotypic switch from alternatively activated antiinflammatory M2 macrophages in lean individuals to classically activated proinflammatory M1 macrophages in obese subjects. However, the molecular mechanism underlying this process remains unclear. In this study we aim to determine whether DNA methyltransferase 3b (DNMT3b) regulates macrophage polarization and inflammation. We found that the expression of DNMT3b was significantly induced in macrophages exposed to the saturated fatty acid stearate, was higher in ATMs isolated from obese mice, but was significantly lower in alternatively activated M2 vs classically activated M1 ATMs, suggesting a role for DNMT3b in regulation of macrophage polarization and inflammation in obesity. DNMT3b knockdown promoted macrophage polarization to alternatively activated M2 phenotype and suppressed macrophage inflammation, whereas overexpressing DNMT3b did the opposite. Importantly, in a macrophage-adipocyte coculture system, we found that DNMT3b knockdown significantly improved adipocyte insulin signaling. The promoter of peroxisome proliferator activated receptor (PPAR)γ1, a key transcriptional factor that regulates macrophage polarization, is enriched with CpG sites. Chromatin immunoprecipitation assays showed that DNMT3b bound to the methylation region at PPARγ1 promoter, which was further enhanced by stearate. Moreover, pyrosequencing analysis revealed that stearate increased DNA methylation at PPARγ1, which was prevented by DNMT3b deficiency. Therefore, our data demonstrate that DNMT3b plays an important role in regulating macrophage polarization through epigenetic mechanisms. In obesity, elevated saturated fatty acids enhance DNMT3b expression, leading to DNA methylation at the PPARγ1 promoter, which may contribute to deregulated adipose tissue macrophage polarization, inflammation, and insulin resistance.

Calcium Promotes Oxidative Stress and Metabolic Dysfunction in Lipotoxicity

Elevated saturated fatty acids (SFA), but not monounsaturated fatty acids, induce apoptosis in a variety of cell types. In H4IIEC3 cells, lipoapoptosis is characterized by decreased ER calcium, increased TCA cycle flux, and the accumulation of reactive oxygen species (ROS). Our hypothesis is SFA‐initiated ER stress results in a net flux of calcium to the mitochondria, which increases oxidative metabolism, leading to ROS‐dependent apoptosis. Our objective is to define the mechanism of deregulated mitochondrial metabolism in promoting lipotoxicity defined by ROS accumulation and O2 uptake as proxy of mitochondrial activity. Scavenging SFA‐induced ROS with antioxidants (vitamin E, n‐acetyl cysteine) reduced apoptosis but not increased mitochondrial activity. Combining SFA and phenformin to inhibit Complex I activity eliminated reduced the lipotoxic phenotype. Additionally, cells were treated with the intracellular calcium chelator BAPTA to examine the role of depleted ER calcium in apoptosis. BAPTA treatments attenuated SFA‐induced ROS accumulation, oxygen consumption, caspase activation, and cell death. Our results suggest that SFA‐induced lipoapoptosis in hepatic cells is dependent on calcium‐stimulated mitochondrial activation and ROS accumulation. This work is funded by NSF Career Award 0955251 (Young).

Mediterranean Diet in Predementia and Dementia Syndromes

There is a critical need to potentially individualize new strategies able to prevent and to slow down the progression of predementia and dementia syndromes. Only recently higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline although the Mediterranean diet (MeDi) combines several foods, micro- and macronutrients already separately proposed as potential protective factors against dementia and predementia syndromes. In fact, elevated saturated fatty acids could have negative effects on age-related cognitive decline and mild cognitive impairment (MCI). Furthermore, at present, epidemiological evidence suggested a possible association among fish consumption, monounsaturated fatty acids and polyunsaturated fatty acids (PUFA) (particularly, n-3 PUFA) and reduced risk of cognitive decline and dementia. Light to moderate alcohol use may be associated with a reduced risk of incident dementia and Alzheimer's disease (AD), while for vascular dementia, cognitive decline, and predementia syndromes the current evidence is only suggestive of a protective effect. Finally, the limited epidemiological evidence available on fruit and vegetable consumption and cognition generally supported a protective role of these macronutrients against cognitive decline, dementia, and AD. Moreover, recent prospective studies provided evidence that higher adherence to a Mediterranean-type diet could be associated with slower cognitive decline, reduced risk of progression from MCI to AD, reduced risk of AD, and decreased all-causes mortality in AD patients. These findings suggested that adherence to the MeDi may affect not only the risk for AD, but also for predementia syndromes and their progression to overt dementia. Nonetheless, at present, no definitive dietary recommendations are possible. However, high levels of consumption of fats from fish, vegetable oils, non-starchy vegetables, low glycemic fruits, and diet low in foods with added sugars and with moderate wine intake should be encouraged. In fact, this dietary advice is in accordance with recommendations for lowering the risk of cardiovascular disease, obesity, diabetes, and hypertension and might open new ways for the prevention and management of cognitive decline and dementia.

Diet and Alzheimer’s disease risk factors or prevention: the current evidence

Preventing or postponing the onset of Alzheimer’s disease (AD) and delaying or slowing its progression would lead to a consequent improvement of health status and quality of life in older age. Elevated saturated fatty acids could have negative effects on age-related cognitive decline and mild cognitive impairment (MCI). Furthermore, at present, epidemiological evidence suggests a possible association between fish consumption, monounsaturated fatty acids and polyunsaturated fatty acids (PUFA; in particular, n-3 PUFA) and a reduced risk of cognitive decline and dementia. Poorer cognitive function and an increased risk of vascular dementia (VaD) were found to be associated with a lower consumption of milk or dairy products. However, the consumption of whole-fat dairy products may be associated with cognitive decline in the elderly. Light-to-moderate alcohol use may be associated with a reduced risk of incident dementia and AD, while for VaD, cognitive decline and predementia syndromes, the current evidence is only suggestive of a protective effect. The limited epidemiological evidence available on fruit and vegetable consumption and cognition generally supports a protective role of these macronutrients against cognitive decline, dementia and AD. Only recently, higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline, although the Mediterranean diet (MeDi) combines several foods, micro- and macro-nutrients already separately proposed as potential protective factors against dementia and predementia syndromes. In fact, recent prospective studies provided evidence that higher adherence to a Mediterranean-type diet could be associated with slower cognitive decline, reduced risk of progression from MCI to AD, reduced risk of AD and a decreased all-cause mortality in AD patients. These findings suggested that adherence to the MeDi may affect not only the risk of AD, but also of predementia syndromes and their progression to overt dementia. Based on the current evidence concerning these factors, no definitive dietary recommendations are possible. However, following dietary advice for lowering the risk of cardiovascular and metabolic disorders, high levels of consumption of fats from fish, vegetable oils, nonstarchy vegetables, low glycemic index fruits and a diet low in foods with added sugars and with moderate wine intake should be encouraged. Hopefully this will open new opportunities for the prevention and management of dementia and AD.

Modulation of palmitate-induced endoplasmic reticulum stress and apoptosis in pancreatic β-cells by stearoyl-CoA desaturase and Elovl6

Induction of endoplasmic reticulum (ER) stress and apoptosis by elevated exogenous saturated fatty acids (FAs) plays a role in the pathogenesis of β-cell dysfunction and loss of islet mass in type 2 diabetes. Regulation of monounsaturated FA (MUFA) synthesis through FA desaturases and elongases may alter the susceptibility of β-cells to saturated FA-induced ER stress and apoptosis. Herein, stearoyl-CoA desaturase (SCD)1 and SCD2 mRNA expression were shown to be induced in islets from prediabetic hyperinsulinemic Zucker diabetic fatty (ZDF) rats, whereas SCD1, SCD2, and fatty acid elongase 6 (Elovl6) mRNA levels were markedly reduced in diabetic ZDF rat islets. Knockdown of SCD in INS-1 β-cells decreased desaturation of palmitate to MUFA, lowered FA partitioning into complex neutral lipids, and increased palmitate-induced ER stress and apoptosis. Overexpression of SCD2 increased desaturation of palmitate to MUFA and attenuated palmitate-induced ER stress and apoptosis. Knockdown of Elovl6 limited palmitate elongation to stearate, increasing palmitoleate production and attenuating palmitate-induced ER stress and apoptosis, whereas overexpression of Elovl6 increased palmitate elongation to stearate and palmitate-induced ER stress and apoptosis. Overall, these data support the hypothesis that enhanced MUFA synthesis via upregulation of SCD2 activity can protect β-cells from elevated saturated FAs, as occurs in prediabetic states. Overt type 2 diabetes is associated with diminished islet expression of SCD and Elovl6, and this can disrupt desaturation of saturated FAs to MUFAs, rendering β-cells more susceptible to saturated FA-induced ER stress and apoptosis.

Dietary Unsaturated Fatty Acids and Risk of Mild Cognitive Impairment

An increasing body of epidemiological evidence suggested that elevated saturated fatty acids could have negative effects on age-related cognitive decline (ARCD) and mild cognitive impairment (MCI). Furthermore, a clear reduction of risk for cognitive decline has been found in population samples with elevated fish consumption, high intake of monounsaturated fatty acids, and polyunsaturated fatty acids (PUFA), particularly n-3 PUFA. In the present article, on the basis of increasing body of evidence from cross-sectional and longitudinal population-based studies, we discussed the issue of the possible impact of dietary PUFA (both n-6 and n-3) on ARCD, MCI, and Alzheimer's disease.

Metabolic memory effect of the saturated fatty acid, palmitate, in monocytes

Hyperglycaemia has a deferred detrimental effect on glucose metabolism, termed “metabolic memory”. Elevated saturated fatty acids promote insulin resistance, hyperglycaemia and associated atherosclerotic complications, but their effect on “metabolic memory” is unknown. Therefore we investigated whether basal and insulin-stimulated (10 −6 M for 12 h) glucose (2-deoxy- d-[ 3H]-glucose) uptake was affected by palmitate pre-treatment human THP-1 monocytes. Palmitate-induced a time-dependent and concentration-dependent inhibition of insulin-stimulated glucose uptake, showing almost complete abolition of the insulin-stimulatory effect with 300 μM palmitate. Basal glucose uptake was unaffected by palmitate. When palmitate was washed out, the inhibitory effect on insulin-stimulated glucose uptake persisted for at least 60 h.

Dietary Fatty Acids and Predementia Syndromes

An increasing body of epidemiological evidence suggests that elevated saturated fatty acids (SFA) could have negative effects on age-related cognitive decline (ARCD). Furthermore, a reduction of risk for cognitive decline and mild cognitive impairment (MCI) has been found in population samples with elevated fish consumption, and high intake of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA), particularly n-3 PUFA. However, recent findings from clinical trials with n-3 PUFA supplementation showed efficacy on depressive symptoms in non–Vapolipoprotein E (APOE) ε4 carriers, and on cognitive symptoms only in very mild Alzheimer's disease (AD) subgroups, MCI patients, and cognitively unimpaired non-APOE ε4 carriers. These data, together with epidemiological evidence, support the idea that n-3 PUFA may play a role in maintaining adequate cognitive functioning in predementia syndromes, but not when the AD process has already taken over. Therefore, at present, no definitive dietary recommendations on fish and unsaturated fatty acids consumption, or lower intake of saturated fat, in relation to the risk for dementia and cognitive decline are possible.

Oxidative stress and non-enzymatic glycation in IgA nephropathy

Approximately 20-50% of IgA nephropathy patients develop end-stage renal disease. We have previously found enhanced oxidative stress and decreased antioxidant capacity in red blood cells of IgA nephropathy patients. In this study we assess oxidative stress, non-enzymatic glycation, oxidative resistance of low-density lipoprotein and its alpha-tocopherol content in these patients. Non-enzymatic glycation and oxidative stress were assessed in 88 IgA nephropathy patients by measuring advanced glycation end products, Nepsilon-carboxymethyl-lysine, thiobarbituric acid reactive substances, oxidative resistance of low-density lipoprotein and its alpha-tocopherol content. Advanced glycation end products (2659 +/- 958 a.u.) and Nepsilon-carboxymethyl-lysine (563 +/- 215 ng/ml) were significantly higher in IgA nephropathy patients with decreased renal function compared to those with normal renal function (p < 0.002) or controls (p < 0.001). Thiobarbituric acid-reactive substances in plasma and associated with low-density lipoprotein were significantly elevated and oxidative resistance of low-density lipoprotein was significantly reduced in all groups of IgA nephropathy patients. There was no significant difference in circulating fluorescent advanced glycation end products, Nepsilon-carboxymethyl-lysine, thiobarbituric acid-reactive substances levels, oxidative resistance of low-density lipoprotein and its alpha-tocopherol content between patients with normal vs. impaired glucose metabolism. Low alpha-tocopherol content of low-density lipoprotein was accompanied with decreased oxidative resistance, depletion in polyunsaturated fatty acids, elevated saturated fatty acids and thiobarbituric acid-reactive substances within low-density lipoprotein suggesting enhanced lipid peroxidation. Decreased oxidative resistance of low-density lipoprotein and enhanced oxidative stress are common features in IgA nephropathy, while increased non-enzymatic glycation occurs as renal function declines.

Veränderungen der Phospholipid- und Triglyzeridzusammensetzung im mütterlichen Blut bei Präeklampsien - Signifikant erniedrigte essentielle Fettsäuren

Purpose: We conducted a study to evaluate the fatty acid status from maternal blood to see the possible roles of lipid metabolism in the pathogenesis of preeclampsia. Patients and Methods : 14 women with preeclampsia and 16 healthy control cases were evaluated. The mean gestational age for the first measurement was 35 in preeclampsia and 36 in controls with comparable body mass index. After the delivery we had another measurement on day five. The absolute level of phospholipid and triglycerid composition was determined after modified Folch lipid extraction with chloroform/ methanol, separation of lipid extract using prepacked Isolute-NH2-colums, transmethylation and gas-liquid chromatography with a capillary colum. Results: In preeclampsia there are elevated non-essential saturated and monounsaturated fatty acids in both lipid classes compared with the control group, combined with a significant hypertriglyceridaemia (4.2 vs. 3.0 mmol/l). Also in the preeclampsia group, significantly lower concentration values in both lipid classes were found for the most important essential fatty acid for neural tissues, the nervonic acid (C22:6n-3) (0.10 vs. 0.19 mmol/l in triglycerid fraction and 0.31 vs. 0.48 mmol/l in phospholipid fraction). Besides this in the triglycerid fraction C 18:2n-6 was decreased in the preeclampsia group (0.21 vs. 0,29 mmol/l). Conclusion: Women with preeclampsia demonstrated higher non-essential and lower essential fatty acid status. The last one may be responsible for creating free radicals, which can destroy endothelial cells. This pattern concerns especially the important neuronal structure fatty acid C22:6n-3. Further investigation is necessary to clarify what the low concentration of nervonic acids means to the fetus. We speculate that changed lipid metabolism may contribute to the aetiology of PE.