scholarly journals Marine omega-3 fatty acids prevent myocardial insulin resistance and metabolic remodeling as induced experimentally by high insulin exposure

2015 ◽  
Vol 308 (4) ◽  
pp. C297-C307 ◽  
Author(s):  
Veronika Franekova ◽  
Yeliz Angin ◽  
Nicole T. H. Hoebers ◽  
Will A. Coumans ◽  
Peter J. Simons ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Insulin Signaling ◽  
Acid Uptake ◽  
Omega 3 ◽  
Rat Cardiomyocytes ◽  
Metabolic Remodeling ◽  
High Insulin

Insulin resistance is an important risk factor for the development of several cardiac pathologies, thus advocating strategies for restoring insulin sensitivity of the heart in these conditions. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), mainly eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3), have been shown to improve insulin sensitivity in insulin-sensitive tissues, but their direct effect on insulin signaling and metabolic parameters in the myocardium has not been reported previously. The aim of this study was therefore to examine the ability of EPA and DHA to prevent insulin resistance in isolated rat cardiomyocytes. Primary rat cardiomyocytes were made insulin resistant by 48 h incubation in high insulin (HI) medium. Parallel incubations were supplemented by 200 μM EPA or DHA. Addition of EPA or DHA to the medium prevented the induction of insulin resistance in cardiomyocytes by preserving the phosphorylation state of key proteins in the insulin signaling cascade and by preventing persistent relocation of fatty acid transporter CD36 to the sarcolemma. Only cardiomyocytes incubated in the presence of EPA, however, exhibited improvements in glucose and fatty acid uptake and cell shortening. We conclude that ω-3 PUFAs protect metabolic and functional properties of cardiomyocytes subjected to insulin resistance-evoking conditions.

scholarly journals Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids

2015 ◽  
Vol 112 (4) ◽  
pp. 1143-1148 ◽  
Author(s):  
Daniel F. Vatner ◽  
Sachin K. Majumdar ◽  
Naoki Kumashiro ◽  
Max C. Petersen ◽  
Yasmeen Rahimi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Insulin Signaling ◽  
Plasma Fatty Acid ◽  
Hepatic Triglyceride ◽  
Triglyceride Synthesis ◽  
Hepatic Glucose ◽  
Acid Esterification ◽  
Fatty Acid Esterification

A central paradox in type 2 diabetes is the apparent selective nature of hepatic insulin resistance—wherein insulin fails to suppress hepatic glucose production yet continues to stimulate lipogenesis, resulting in hyperglycemia, hyperlipidemia, and hepatic steatosis. Although efforts to explain this have focused on finding a branch point in insulin signaling where hepatic glucose and lipid metabolism diverge, we hypothesized that hepatic triglyceride synthesis could be driven by substrate, independent of changes in hepatic insulin signaling. We tested this hypothesis in rats by infusing [U-13C] palmitate to measure rates of fatty acid esterification into hepatic triglyceride while varying plasma fatty acid and insulin concentrations independently. These experiments were performed in normal rats, high fat-fed insulin-resistant rats, and insulin receptor 2′-O-methoxyethyl chimeric antisense oligonucleotide-treated rats. Rates of fatty acid esterification into hepatic triglyceride were found to be dependent on plasma fatty acid infusion rates, independent of changes in plasma insulin concentrations and independent of hepatocellular insulin signaling. Taken together, these results obviate a paradox of selective insulin resistance, because the major source of hepatic lipid synthesis, esterification of preformed fatty acids, is primarily dependent on substrate delivery and largely independent of hepatic insulin action.

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 pNFκB-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.

scholarly journals Oxidised metabolites of the omega-6 fatty acid linoleic acid activate dFOXO

2020 ◽  
Vol 3 (2) ◽  
pp. e201900356
Author(s):  
So Yeon Kwon ◽  
Karen Massey ◽  
Mark A Watson ◽  
Tayab Hussain ◽  
Giacomo Volpe ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Insulin Signaling ◽  
Saturated Fatty Acids ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Lipid Mediator ◽  
Omega 3 ◽  
Omega 6

Obesity-induced inflammation, or meta-inflammation, plays key roles in metabolic syndrome and is a significant risk factor in diabetes and cardiovascular disease. To investigate causal links between obesity, meta-inflammation, and insulin signaling we established a Drosophila model to determine how elevated dietary fat and changes in the levels and balance of saturated fatty acids (SFAs) and polyunsaturated fatty acids (PUFAs) influence inflammation. We observe negligible effect of saturated fatty acid on inflammation but marked enhancement or suppression by omega-6 and omega-3 PUFAs, respectively. Using combined lipidomic and genetic analysis, we show omega-6 PUFA enhances meta-inflammation by producing linoleic acid–derived lipid mediator 9-hydroxy-octadecadienoic acid (9-HODE). Transcriptome analysis reveals 9-HODE functions by regulating FOXO family transcription factors. We show 9-HODE activates JNK, triggering FOXO nuclear localisation and chromatin binding. FOXO TFs are important transducers of the insulin signaling pathway that are normally down-regulated by insulin. By activating FOXO, 9-HODE could antagonise insulin signaling providing a molecular conduit linking changes in dietary fatty acid balance, meta-inflammation, and insulin resistance.

scholarly journals Dietary fat and insulin action in humans

2000 ◽  
Vol 83 (S1) ◽  
pp. S91-S96 ◽  
Author(s):  
Bengt Vessby
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Insulin Sensitivity ◽  
Acid Composition ◽  
Δ5 Desaturase ◽  
Reduced Activity

A high intake of fat may increase the risk of obesity. Obesity, especially abdominal obesity, is an important determinant of the risk of developing insulin resistance and non-insulin-dependent diabetes mellitus. It is suggested that a high proportion of fat in the diet is associated with impaired insulin sensitivity and an increased risk of developing diabetes, independent of obesity and body fat localization, and that this risk may be influenced by the type of fatty acids in the diet. Cross-sectional studies show significant relationships between the serum lipid fatty acid composition, which at least partly mirrors the quality of the fatty acids in the diet, and insulin sensitivity. Insulin resistance, and disorders characterized by insulin resistance, are associated with a specific fatty acid pattern of the serum lipids with increased proportions of palmitic (16 : 0) and palmitoleic acids (16 : 1 n-7) and reduced levels of linoleic acid (18 : 2 n-6). The metabolism of linoleic acid seems to be disturbed with increased proportions of dihomo-gamma linolenic acid (20 : 3 n-6) and a reduced activity of the Δ5 desaturase, while the activities of the Δ9 and Δ6 desaturases appear to be increased. The skeletal muscle is the main determinant of insulin sensitivity. Several studies have shown that the fatty acid composition of the phosholipids of the skeletal muscle cell membranes is closely related to insulin sensitivity. An increased saturation of the membrane fatty acids and a reduced activity of Δ5 desaturase have been associated with insulin resistance. There are several possible mechanisms which could explain this relationship. The fatty acid composition of the lipids in serum and muscle is influenced by diet, but also by the degree of physical activity, genetic disposition, and possibly fetal undernutrition. However, controlled dietary intervention studies in humans investigating the effects of different types of fatty acids on insulin sensitivity have so far been negative.

Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss

1999 ◽  
Vol 277 (6) ◽  
pp. E1130-E1141 ◽  
Author(s):  
David E. Kelley ◽  
Bret Goodpaster ◽  
Rena R. Wing ◽  
Jean-Aime Simoneau
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Weight Loss ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Fat Oxidation ◽  
Acid Uptake ◽  
Obese Subjects

The current study was undertaken to investigate fatty acid metabolism by skeletal muscle to examine potential mechanisms that could lead to increased muscle triglyceride in obesity. Sixteen lean and 40 obese research volunteers had leg balance measurement of glucose and free fatty acid (FFA) uptake (fractional extraction of [9,103H]oleate) and indirect calorimetry across the leg to determine substrate oxidation during fasting and insulin-stimulated conditions. Muscle obtained by percutaneous biopsy had lower carnitine palmitoyl transferase (CPT) activity and oxidative enzyme activity in obesity ( P < 0.05). During fasting conditions, obese subjects had an elevated leg respiratory quotient (RQ, 0.83 ± 0.02 vs. 0.90 ± 0.01; P < 0.01) and reduced fat oxidation but similar FFA uptake across the leg. During insulin infusions, fat oxidation by leg tissues was suppressed in lean but not obese subjects; rates of FFA uptake were similar. Fasting values for leg RQ correlated with insulin sensitivity ( r = −0.57, P < 0.001). Thirty-two of the obese subjects were restudied after weight loss (WL, −14.0 ± 0.9 kg); insulin sensitivity and insulin suppression of fat oxidation improved ( P < 0.01), but fasting leg RQ (0.90 ± 0.02 vs. 0.90 ± 0.02, pre-WL vs. post-WL) and muscle CPT activity did not change. The findings suggest that triglyceride accumulation in skeletal muscle in obesity derives from reduced capacity for fat oxidation and that inflexibility in regulating fat oxidation, more than fatty acid uptake, is related to insulin resistance.

scholarly journals A new leptin-mediated mechanism for stimulating fatty acid oxidation: a pivotal role for sarcolemmal FAT/CD36

2016 ◽  
Vol 474 (1) ◽  
pp. 149-162 ◽  
Author(s):  
Iman Momken ◽  
Adrian Chabowski ◽  
Ellen Dirkx ◽  
Miranda Nabben ◽  
Swati S. Jain ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Plasma Membrane ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Fatty Acid Uptake ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Rat Cardiomyocytes ◽  
Compound C ◽  
Ampk Phosphorylation

Leptin stimulates fatty acid oxidation in muscle and heart; but, the mechanism by which these tissues provide additional intracellular fatty acids for their oxidation remains unknown. We examined, in isolated muscle and cardiac myocytes, whether leptin, via AMP-activated protein kinase (AMPK) activation, stimulated fatty acid translocase (FAT/CD36)-mediated fatty acid uptake to enhance fatty acid oxidation. In both mouse skeletal muscle and rat cardiomyocytes, leptin increased fatty acid oxidation, an effect that was blocked when AMPK phosphorylation was inhibited by adenine 9-β-d-arabinofuranoside or Compound C. In wild-type mice, leptin induced the translocation of FAT/CD36 to the plasma membrane and increased fatty acid uptake into giant sarcolemmal vesicles and into cardiomyocytes. In muscles of FAT/CD36-KO mice, and in cardiomyocytes in which cell surface FAT/CD36 action was blocked by sulfo-N-succinimidyl oleate, the leptin-stimulated influx of fatty acids was inhibited; concomitantly, the normal leptin-stimulated increase in fatty acid oxidation was also prevented, despite the normal leptin-induced increase in AMPK phosphorylation. Conversely, in muscle of AMPK kinase-dead mice, leptin failed to induce the translocation of FAT/CD36, along with a failure to stimulate fatty acid uptake and oxidation. Similarly, when siRNA was used to reduce AMPK in HL-1 cardiomyocytes, leptin failed to induce the translocation of FAT/CD36. Our studies have revealed a novel mechanism of leptin-induced fatty acid oxidation in muscle tissue; namely, this process is dependent on the activation of AMPK to induce the translocation of FAT/CD36 to the plasma membrane, thereby stimulating fatty acid uptake. Without increasing this leptin-stimulated, FAT/CD36-dependent fatty acid uptake process, leptin-stimulated AMPK phosphorylation does not enhance fatty acid oxidation.

EFFECT OF GINGER, LEMURU FISH OIL SAPONIFICATION AND OLIVE OIL ON COMPOSITION FATTY ACID OF BEEF

2014 ◽  
Vol 4 (1) ◽  
pp. 31-39
Author(s):  
Siwitri Kadarsih
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fish Oil ◽  
Olive Oil ◽  
Rice Bran ◽  
Dry Matter ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Omega 3 ◽  
Omega 6

The objective was to get beef that contain unsaturated fatty acids (especially omega 3 and 6), so as to improve intelligence, physical health for those who consume. The study design using CRD with 3 treatments, each treatment used 4 Bali cattle aged approximately 1.5 years. Observations were made 8 weeks. Pasta mixed with ginger provided konsentrat. P1 (control); P2 (6% saponification lemuru fish oil, olive oil 1%; rice bran: 37.30%; corn: 62.70%; KLK: 7%, ginger paste: 100 g); P3 (lemuru fish oil saponification 8%, 2% olive oil; rice bran; 37.30; corn: 62.70%; KLK: 7%, ginger paste: 200 g). Konsentrat given in the morning as much as 1% of the weight of the cattle based on dry matter, while the grass given a minimum of 10% of the weight of livestock observation variables include: fatty acid composition of meat. Data the analyzies qualitative. The results of the study showed that the composition of saturated fatty acids in meat decreased and an increase in unsaturated fatty acids, namely linoleic acid (omega 6) and linolenic acid (omega 3), and deikosapenta deikosaheksa acid.Keywords : 

scholarly journals Enzyme-Assisted Extraction of Fish Oil from Whole Fish and by-Products of Baltic Herring (Clupea harengus membras)

Foods ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1811
Author(s):  
Ella Aitta ◽  
Alexis Marsol-Vall ◽  
Annelie Damerau ◽  
Baoru Yang
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fish Oil ◽  
Crude Oil ◽  
Proteolytic Enzymes ◽  
Clupea Harengus ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Baltic Herring ◽  
By Products

Baltic herring (Clupea harengus membras) is one of the most abundant commercially caught fish species from the Baltic Sea. Despite the high content of fat and omega-3 fatty acids, the consumption of Baltic herring has decreased dramatically over the last four decades, mostly due to the small sizes and difficulty in processing. At the same time there is an increasing global demand for fish and fish oil rich in omega-3 fatty acids. This study aimed to investigate enzyme-assisted oil extraction as an environmentally friendly process for valorizing the underutilized fish species and by-products to high quality fish oil for human consumption. Three different commercially available proteolytic enzymes (Alcalase®, Neutrase® and Protamex®) and two treatment times (35 and 70 min) were investigated in the extraction of fish oil from whole fish and by-products from filleting of Baltic herring. The oil quality and stability were studied with peroxide- and p-anisidine value analyses, fatty acid analysis with GC-FID, and volatile compounds with HS-SPME-GC-MS. Overall, longer extraction times led to better oil yields but also increased oxidation of the oil. For whole fish, the highest oil yields were from the 70-min extractions with Neutrase and Protamex. Protamex extraction with 35 min resulted in the best fatty acid composition with the highest content of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) but also increased oxidation compared to treatment with other enzymes. For by-products, the highest oil yield was obtained from the 70-min extraction with Protamex without significant differences in EPA and DHA contents among the oils extracted with different enzymes. Oxidation was lowest in the oil produced with 35-min treatment using Neutrase and Protamex. This study showed the potential of using proteolytic enzymes in the extraction of crude oil from Baltic herring and its by-products. However, further research is needed to optimize enzymatic processing of Baltic herring and its by-products to improve yield and quality of crude oil.

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