scholarly journals Cultured hypothalamic neurons are resistant to inflammation and insulin resistance induced by saturated fatty acids

2010 ◽  
Vol 298 (6) ◽  
pp. E1122-E1130 ◽  
Author(s):  
Sun Ju Choi ◽  
Francis Kim ◽  
Michael W. Schwartz ◽  
Brent E. Wisse
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Saturated Fatty Acid ◽  
Cell Lines ◽  
Saturated Fatty Acids ◽  
Neuronal Cell ◽  
Acid Exposure ◽  
Inflammatory Signaling ◽  
Hypothalamic Neurons

Hypothalamic inflammation induced by high-fat feeding causes insulin and leptin resistance and contributes to the pathogenesis of obesity. Since in vitro exposure to saturated fatty acids causes inflammation and insulin resistance in many cultured cell types, we determined how cultured hypothalamic neurons respond to this stimulus. Two murine hypothalamic neuronal cell cultures, N43/5 and GT1–7, were exposed to escalating concentrations of saturated fatty acids for up to 24 h. Harvested cells were evaluated for activation of inflammation by gene expression and protein content. Insulin-treated cells were evaluated for induction of markers of insulin receptor signaling (p-IRS, p-Akt). In both hypothalamic cell lines, inflammation was induced by prototypical inflammatory mediators LPS and TNFα, as judged by induction of IκBα (3- to 5-fold) and IL-6 (3- to 7-fold) mRNA and p-IκBα protein, and TNFα pretreatment reduced insulin-mediated p-Akt activation by 30% ( P < 0.05). By comparison, neither mixed saturated fatty acid (100, 250, or 500 μM for ≤6 h) nor palmitate exposure alone (200 μM for ≤24 h) caused inflammatory activation or insulin resistance in cultured hypothalamic neurons, whereas they did in control muscle and endothelial cell lines. Despite the lack of evidence of inflammatory signaling, saturated fatty acid exposure in cultured hypothalamic neurons causes endoplasmic reticulum stress, induces mitogen-activated protein kinase, and causes apoptotic cell death with prolonged exposure. We conclude that saturated fatty acid exposure does not induce inflammatory signaling or insulin resistance in cultured hypothalamic neurons. Therefore, hypothalamic neuronal inflammation in the setting of DIO may involve an indirect mechanism mediated by saturated fatty acids on nonneuronal cells.

scholarly journals MLK3 promotes metabolic dysfunction induced by saturated fatty acid-enriched diet

2013 ◽  
Vol 305 (4) ◽  
pp. E549-E556 ◽  
Author(s):  
Vidya Gadang ◽  
Rohit Kohli ◽  
Andriy Myronovych ◽  
David Y. Hui ◽  
Diego Perez-Tilve ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Saturated Fatty Acid ◽  
Saturated Fatty Acids ◽  
Low Grade ◽  
Metabolic Dysfunction ◽  
Jnk Activation

Saturated fatty acids activate the c-Jun NH2-terminal kinase (JNK) pathway, resulting in chronic low-grade inflammation and the development of insulin resistance. Mixed-lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase (MAP3K) that mediates JNK activation in response to saturated fatty acids in vitro; however, the exact mechanism for diet-induced JNK activation in vivo is not known. Here, we have used MLK3-deficient mice to examine the role of MLK3 in a saturated-fat diet model of obesity. MLK3-KO mice fed a high-fat diet enriched in medium-chain saturated fatty acids for 16 wk had decreased body fat compared with wild-type (WT) mice due to increased energy expenditure independently of food consumption and physical activity. Moreover, MLK3 deficiency attenuated palmitate-induced JNK activation and M1 polarization in bone marrow-derived macrophages in vitro, and obesity induced JNK activation, macrophage infiltration into adipose tissue, and expression of proinflammatory cytokines in vivo. In addition, loss of MLK3 improved insulin resistance and decreased hepatic steatosis. Together, these data demonstrate that MLK3 promotes saturated fatty acid-induced JNK activation in vivo and diet-induced metabolic dysfunction.

scholarly journals Circulating fatty acid profiles are associated with protein energy wasting in maintenance hemodialysis patients: a cross-sectional study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ban-Hock Khor ◽  
◽  
Sharmela Sahathevan ◽  
Ayesha Sualeheen ◽  
Mohammad Syafiq Md Ali ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Nutritional Status ◽  
Serum Albumin ◽  
Saturated Fatty Acids ◽  
Maintenance Hemodialysis ◽  
Model Assessment ◽  
Cross Sectional ◽  
Markers Of Inflammation

AbstractThe metabolic impact of circulating fatty acids (FAs) in patients requiring hemodialysis (HD) is unknown. We investigated the associations between plasma triglyceride (TG) FAs and markers of inflammation, insulin resistance, nutritional status and body composition. Plasma TG-FAs were measured using gas chromatography in 341 patients on HD (age = 55.2 ± 14.0 years and 54.3% males). Cross-sectional associations of TG-FAs with 13 markers were examined using multivariate linear regression adjusted for potential confounders. Higher levels of TG saturated fatty acids were associated with greater body mass index (BMI, r = 0.230), waist circumference (r = 0.203), triceps skinfold (r = 0.197), fat tissue index (r = 0.150), serum insulin (r = 0.280), and homeostatic model assessment of insulin resistance (r = 0.276), but lower malnutrition inflammation score (MIS, r =  − 0.160). Greater TG monounsaturated fatty acid levels were associated with lower lean tissue index (r =  − 0.197) and serum albumin (r =  − 0.188), but higher MIS (r = 0.176). Higher levels of TG n-3 polyunsaturated fatty acids (PUFAs) were associated with lower MIS (r =  − 0.168) and interleukin-6 concentrations (r =  − 0.115). Higher levels of TG n-6 PUFAs were associated with lower BMI (r =  − 0.149) but greater serum albumin (r = 0.112). In conclusion, TG monounsaturated fatty acids were associated with poor nutritional status, while TG n-3 PUFAs were associated with good nutritional status. On the other hand, TG saturated fatty acids and TG n-6 PUFAs had both favorable and unfavorable associations with nutritional parameters.

scholarly journals The n-10 Fatty Acids Family in the Lipidome of Human Prostatic Adenocarcinoma Cell Membranes and Extracellular Vesicles

2020 ◽  
Author(s):  
Carla Ferreri ◽  
Anna Sansone ◽  
Sandra Buratta ◽  
Lorena Urbanelli ◽  
Eva Costanzi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cell Lines ◽  
Cancer Cell ◽  
Extracellular Vesicles ◽  
Cell Membranes ◽  
Saturated Fatty Acids ◽  
Prostatic Adenocarcinoma ◽  
Fatty Acid Isomer ◽  
Adenocarcinoma Cell

A new pathway leading to the n-10 fatty acid series has been recently evidenced, starting from sapienic acid - a monounsaturated fatty acid (MUFA) resulting from the transformation of palmitic acid by delta-6 desaturase. Sapienic acid attracts attention as novel marker of cancer cell plasticity. Here, we analyzed fatty acids including the n-10 fatty acid contents, and compared for the first time cell membranes and the corresponding extracellular vesicles (EV) of two human prostatic adenocarcinoma cell lines of different aggressiveness (PC3 and LNCaP). The n-10 components were 9-13% of the total fatty acids in both cancer cell lines and EVs, with total MUFA levels significantly higher in EVs of the most aggressive cell type (PC3). High sapienic/palmitoleic ratios indicated the preference for delta-6 vs. delta-9 desaturase enzymatic activity in these cell lines. The expressions analysis of enzymes involved in desaturation and elongation by qRT-PCR showed a higher desaturase activity in PC3 and a higher elongase activity toward polyunsaturated fatty acids than toward saturated fatty acids, compared to LNCaP cells. Our results improve the present knowledge in cancer fatty acid metabolism and lipid phenotypes, highlighting EV lipidomics to monitor positional fatty acid isomer profiles and MUFA levels in cancer.

scholarly journals Mitochondrial dysfunction in insulin resistance: differential contributions of chronic insulin and saturated fatty acid exposure in muscle cells

2012 ◽  
Vol 32 (5) ◽  
pp. 465-478 ◽  
Author(s):  
Chenjing Yang ◽  
Cho Cho Aye ◽  
Xiaoxin Li ◽  
Angels Diaz Ramos ◽  
Antonio Zorzano ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Oxygen Consumption ◽  
Fatty Acid ◽  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Saturated Fatty Acid ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Acid Exposure ◽  
High Insulin

Mitochondrial dysfunction has been associated with insulin resistance, obesity and diabetes. Hyperinsulinaemia and hyperlipidaemia are hallmarks of the insulin-resistant state. We sought to determine the contributions of high insulin and saturated fatty acid exposure to mitochondrial function and biogenesis in cultured myocytes. Differentiated C2C12 myotubes were left untreated or exposed to chronic high insulin or high palmitate. Mitochondrial function was determined assessing: oxygen consumption, mitochondrial membrane potential, ATP content and ROS (reactive oxygen species) production. We also determined the expression of several mitochondrial genes. Chronic insulin treatment of myotubes caused insulin resistance with reduced PI3K (phosphoinositide 3-kinase) and ERK (extracellular-signal-regulated kinase) signalling. Insulin treatment increased oxygen consumption but reduced mitochondrial membrane potential and ROS production. ATP cellular levels were maintained through an increased glycolytic rate. The expression of mitochondrial OXPHOS (oxidative phosphorylation) subunits or Mfn-2 (mitofusin 2) were not significantly altered in comparison with untreated cells, whereas expression of PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α) and UCPs (uncoupling proteins) were reduced. In contrast, saturated fatty acid exposure caused insulin resistance, reducing PI3K (phosphoinositide 3-kinase) and ERK (extracellular-signal-regulated kinase) activation while increasing activation of stress kinases JNK (c-Jun N-terminal kinase) and p38. Fatty acids reduced oxygen consumption and mitochondrial membrane potential while up-regulating the expression of mitochondrial ETC (electron chain complex) protein subunits and UCP proteins. Mfn-2 expression was not modified by palmitate. Palmitate-treated cells also showed a reduced glycolytic rate. Taken together, our findings indicate that chronic insulin and fatty acid-induced insulin resistance differentially affect mitochondrial function. In both conditions, cells were able to maintain ATP levels despite the loss of membrane potential; however, different protein expression suggests different adaptation mechanisms.

Carnitine palmitoyltransferase 1A prevents fatty acid-induced adipocyte dysfunction through suppression of c-Jun N-terminal kinase

2011 ◽  
Vol 435 (3) ◽  
pp. 723-732 ◽  
Author(s):  
Xuefei Gao ◽  
Kuai Li ◽  
Xiaoyan Hui ◽  
Xiangping Kong ◽  
Gary Sweeney ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Cell Lines ◽  
Specific Inhibitor ◽  
Physiological Role ◽  
Carnitine Palmitoyltransferase ◽  
Acid Uptake ◽  
Pharmacological Inhibition

The adipocyte is the principal cell type for fat storage. CPT1 (carnitine palmitoyltransferase-1) is the rate-limiting enzyme for fatty acid β-oxidation, but the physiological role of CPT1 in adipocytes remains unclear. In the present study, we focused on the specific role of CPT1A in the normal functioning of adipocytes. Three 3T3-L1 adipocyte cell lines stably expressing hCPT1A (human CPT1A) cDNA, mouse CPT1A shRNA (short-hairpin RNA) or GFP (green fluorescent protein) were generated and the biological functions of these cell lines were characterized. Alteration in CPT1 activity, either by ectopic overexpression or pharmacological inhibition using etomoxir, did not affect adipocyte differentiation. However, overexpression of hCPT1A significantly reduced the content of intracellular NEFAs (non-esterified fatty acids) compared with the control cells when adipocytes were challenged with fatty acids. The changes were accompanied by an increase in fatty acid uptake and a decrease in fatty acid release. Interestingly, CPT1A protected against fatty acid-induced insulin resistance and expression of pro-inflammatory adipokines such as TNF-α (tumour necrosis factor-α) and IL-6 (interleukin-6) in adipocytes. Further studies demonstrated that JNK (c-Jun N terminal kinase) activity was substantially suppressed upon CPT1A overexpression, whereas knockdown or pharmacological inhibition of CPT1 caused a significant enhancement of JNK activity. The specific inhibitor of JNK SP600125 largely abolished the changes caused by the shRNA- and etomoxir-mediated decrease in CPT1 activity. Moreover, C2C12 myocytes co-cultured with adipocytes pre-treated with fatty acids displayed altered insulin sensitivity. Taken together, our findings have identified a favourable role for CPT1A in adipocytes to attenuate fatty acid-evoked insulin resistance and inflammation via suppression of JNK.

scholarly journals “Insulin-Like” Effects of Palmitate Might Contribute to the Development of Insulin Resistance in Hypothalamic Neurons

2018 ◽  
Author(s):  
Martin Benzler ◽  
Jonas Benzler ◽  
Sigrid Stoehr ◽  
Cindy Hempp ◽  
Mohammed Z. Rizwan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Saturated Fatty Acids ◽  
Dependent Manner ◽  
Omega 3 ◽  
Protein Levels

Saturated fatty acids are implicated in the development of metabolic diseases, including obesity and type 2 diabetes. There is evidence, however, that polyunsaturated fatty acids can counteract the pathogenic effects of saturated fatty acids. To gain insight into the early molecular mechanisms by which fatty acids influence hypothalamic inflammation and insulin resistance, we performed time-course experiments in a hypothalamic cell line, using different durations of treatment with the saturated fatty acid palmitate, and the omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA). Western blot analysis revealed that palmitate elevated the protein levels of phospho(p)AKT in a time-dependent manner. This effect seems involved in the pathogenicity of palmitate, as temporary inhibition of the PI3K/AKT pathway by selective PI3K inhibitors prevented palmitate-induced insulin resistance. Similarly to palmitate, DHA also increased levels of pAKT, but to a weaker extent. Co-administration of DHA with palmitate decreased pAKT close to the basal level after 8 h, and prevented palmitate-induced insulin resistance after 12 h. Measurement of the inflammatory markers pJNK and pNF&kappa;B-p65 revealed tonic elevation of both markers in the presence of palmitate alone. DHA alone transiently induced elevation of pJNK, returning to basal levels by 12 h treatment. Co-administration of DHA with palmitate prevented palmitate-induced inflammation after 12 h, but not at earlier time points.

Sire and dam breed effects on fatty acid profiles in the longissimus dorsi muscle and subcutaneous fat of beef cattle

2006 ◽  
Vol 46 (7) ◽  
pp. 913 ◽  
Author(s):  
J. F. Graham ◽  
E. Bernaud ◽  
M. P. B. Deland
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Saturated Fatty Acid ◽  
Saturated Fatty Acids ◽  
Subcutaneous Fat ◽  
Intramuscular Fat ◽  
Fatty Acid Ratio ◽  
Longissimus Dorsi Muscle ◽  
Acid Ratio ◽  
Saturated Fatty Acid Ratio

This study investigated the effect of sire and dam breed on the fatty acid profiles of muscle and subcutaneous fat in beef cattle. Seven hundred and ninety-three steer and 222 female progeny derived from mating Angus and Hereford cows to Angus, Hereford, Limousin and Simmental bulls, were slaughtered at around 2 years of age (about 540 kg liveweight). The mean fat content of the longissimus dorsi muscle ranged from 4.6% for the Limousin-sired cattle to 6.0% for the Angus-sired cattle. Breed differences occurred in the majority of fatty acids from the intramuscular fat, but fewer differences were observed from the subcutaneous fat. The Limousin- and Simmental-sired progeny had less (P<0.001) saturated fat and more (P<0.001) unsaturated intramuscular fat compared with the Angus- and Hereford-sired cattle. The Angus and Simmental cattle had more (P<0.001) monounsaturates than the Limousin and Hereford cattle. There were differences (P<0.001) in the level of intramuscular polyunsaturates between all 4 sire-breeds, the Limousin having the highest and Angus the lowest. Simmental progeny had significantly higher levels of polyunsaturated fatty acids, compared with the Hereford-sired progeny, as well as a higher monousaturated : saturated fatty acid ratio. Hereford-sired progeny had a lower (P<0.001) monousaturated : saturated fatty acid ratio in the intramuscular fat. Intramuscular fatty acids were affected by dam breed, with progeny of Hereford cows having a higher percentage of unsaturated fatty acids (P = 0.015), lower saturated fatty acids (P = 0.011), and a higher monousaturated : saturated fatty acid ratio (P = 0.028) than those of Angus cows. There was no effect of dam breed on the totals of the different fatty acid groups in the subcutaneous fat. The subcutaneous fat had higher levels of saturated fatty acids and lower levels of unsaturated and polyunsaturated fatty acids compared with the intramuscular fat. Although the differences reported were generally small, it would seem that there may be scope to utilise these genetic differences to produce meat with more desirable fatty acid characteristics.

Correlation between saturated fatty acid chain-length and intermolecular forces determined with terahertz spectroscopy

2019 ◽  
Vol 55 (25) ◽  
pp. 3670-3673 ◽  
Author(s):  
Shuting Fan ◽  
Michael T. Ruggiero ◽  
Zihui Song ◽  
Zhengfang Qian ◽  
Vincent P. Wallace
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Ab Initio ◽  
Chain Length ◽  
Intermolecular Interactions ◽  
Saturated Fatty Acid ◽  
Terahertz Spectroscopy ◽  
Saturated Fatty Acids ◽  
Intermolecular Forces ◽  
Fatty Acid Chain

Chain-length dependent intermolecular interactions of saturated fatty acids are directly probed with THz-TDS and confirmed by ab initio calculations.

Genotypic and environmental effects on saturated fatty acid concentration of canola grown in Manitoba

2004 ◽  
Vol 84 (3) ◽  
pp. 749-756 ◽  
Author(s):  
C. A. McCartney ◽  
R. Scarth ◽  
P. B. E. McVetty ◽  
J. K. Daun
Keyword(s):  
Fatty Acids ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Saturated Fatty Acid ◽  
Acid Concentration ◽  
Protein Concentration ◽  
Saturated Fatty Acids ◽  
Fatty Acid Concentration ◽  
Oil Concentration ◽  
Main Effects

The low saturated fatty acid concentration of canola oil relative to other vegetable oils has resulted in a favourable market share for canola. Understanding the effects of genotype and environment on saturated fatty acid concentration will facilitate Brassica napus breeding efforts aimed at maintaining or reducing saturate levels in the seed oil. Canola-quality B. napus samples from the Manitoba Crop Variety Evaluation Team (MCVET) trials in 1999, 2000 and 2001 were tested for fatty acid composition, oil concentration and protein concentration. Weather data were obtained from nearby weather stations. The majority of the variation in total saturates for the cultivars studied was attributed to variation in palmitic acid (C16:0) due to the genotype main effect and variation in stearic acid (C18:0) due to the genotype and environment main effects. The variation due to the genotype × environment interaction was small relative to the main effects for the individual saturated fatty acids. C18:0 and arachidic (C20:0) acid concentrations were correlated between genotypes, suggesting pleiotropy or that these traits are controlled by linked genes in the cultivars tested. The data also suggested that C16:0 and C18:0 acid concentrations are controlled by different genes. C18:0, C20:0 and behenic (C22:0) acid concentrations were correlated across environments, but did not correlate with C16:0 concentration. Relationships between weather variables and fatty acid composition, oil concentration and protein concentration were not established. Additive Main effects and Multiplicative Interaction (AMMI) analysis revealed that some canola cultivars were more stable than others with regard to total saturates over environments. Key words: Genotype, environment, seed quality, saturated fatty acids, canola, Brassica napus

scholarly journals The Ratio of Unsaturated to Saturated Fatty Acids is a Distinguishing Feature of NAFLD in Subjects With Metabolic Disease

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A421-A421
Author(s):  
John N Falcone ◽  
Maurice A Hurd ◽  
Sonal Kumar ◽  
Michele Yeung ◽  
Carolyn Newberry ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Liver Disease ◽  
Saturated Fatty Acids ◽  
The Other ◽  
Acid Index

Abstract Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease affecting at least a quarter of the world’s population. NAFLD is commonly associated with other metabolic conditions such as insulin resistance, type 2 diabetes, obesity, and dyslipidemia. Given the liver’s prominent role in regulating glucose and lipid homeostasis, we hypothesized that subjects with NAFLD have a distinct profile of blood analytes. This investigation examines the association between NAFLD and circulating markers of glucose and lipid metabolism in order to identify a NAFLD-specific metabolite panel that can be used as a predictive biomarker in future studies. We are performing a cross-sectional study in 500 subjects to identify genetic and hormonal factors that correlate with the presence of NAFLD. This abstract reports a preliminary analysis of the results from the first 45 subjects enrolled. Fasting blood samples were collected from 31 subjects with NAFLD and 14 subjects with other metabolic diseases (‘Other’) and without radiologic evidence of NAFLD. The following analytes were measured: serum alanine aminotransferase (ALT), total cholesterol, direct-LDL, HDL, triglycerides, ApoB, small dense LDL-C (sdLDL), VLDL, Lp(a), cholesterol absorption/production markers (beta-sitosterol, campesterol, lathosterol, and desmosterol), glucose, insulin, hemoglobin A1C, adiponectin, hs-CRP, and fatty acids (saturated and unsaturated). Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from glucose and insulin levels, and fatty acids were batched together by structural similarity and reported as indices. The groups were compared using multiple t-tests or the Kolmogorov-Smirnov test when data were non-parametric. The NAFLD group had a mean age 48.4 ± 12.9 yrs and BMI 32.9 ± 6.6 kg/m2. These participants were 61% female and 58% had dyslipidemia, 25% pre-diabetes, and 25% type 2 diabetes. The Other group had a mean age 49.9 ± 12.9 yrs and BMI 39.1 ± 15.6 kg/m2. They were 64% female and 57% had dyslipidemia, 14% pre-diabetes, and 21% type 2 diabetes. ALT was higher in the NAFLD group (55 ± 40 vs 27 ± 22 IU/L, P&lt;0.001). Intriguingly, the saturated fatty acid index was elevated in the NAFLD group (32.5 ± 1.9 vs 30.1 ± 2.2 %, P&lt;0.05), and the omega-6 fatty acid index was elevated in the Other group (42.9 ± 3.7 vs 38.5 ± 4.7 %, P&lt;0.05). These changes led to an unsaturated/saturated fatty acid ratio that was significantly lower in the NAFLD group (2.0 ± 0.1 vs 2.3 ± 0.2, P&lt;0.01). There were no other significant differences in the blood metabolites and hormones. In this small sample comparing subjects with metabolic disease with and without NAFLD, levels of ALT and the ratio of circulating unsaturated/saturated fatty acids are distinguishing features of NAFLD. These may be helpful measures to identify subjects with metabolic disease that require further evaluation for NAFLD.

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