scholarly journals Insulin resistance: the conflict between biological settings of energy metabolism and human lifestyle (a glance at the problem from evolutionary viewpoint)

2016 ◽  
Vol 19 (4) ◽  
pp. 286-294 ◽  
Author(s):  
Vladimir Nicolaevich Titov ◽  
Vladimir Pavlovich Shirinsky
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Atp Synthesis ◽  
Insulin Resistance Syndrome ◽  
Dietary Fatty Acids ◽  
Striated Muscles ◽  
Energy Deficiency ◽  
Atp Production

A biological function of the phylogenetically late humoral mediator insulin is to provide energy substrates for locomotion, i.e. movement resulting from contraction of striated muscles. Insulin is able to meet this evolutionary demand of an organism by means of the effective ATP production in the mitochondria. Exogenous fatty acids, optimised endogenous fatty acids produced from glucose and glucose itself are the major substrates for ATP synthesis. Cells stimulated by insulin produce ω-9 С18:1 oleic acid from glucose. This fatty acid is oxidised by the mitochondria at a higher rate than exogenous and endogenous C16:0 palmitic fatty acid. In the normal state of insulin system and mitochondria, the frequent cause of insulin resistance is the non-optimal properties of dietary fatty acids supplied for oxidation by the mitochondria. Dietary excess of saturated palmitic fatty acid over monogenic oleic fatty acid causes insulin resistance to develop. Insulin resistance syndrome is the condition of in vivo energy deficiency and insufficient production of ATP for the realisation of the biological adaptation and compensation. Insulin effectively inhibits lipolysis only in phylogenetically late subcutaneous adipocytes but not in phylogenetically early visceral fat cells of the omentum. Discrepancy in the regulation of energy substrate metabolism against the background of a ‘relative biological perfection’ of higher mammals is the aetiological basis of insulin resistance.

100th Anniversary of the discovery of insulin Perspective: Insulin and Adipose Tissue Fatty Acid Metabolism

2021 ◽  
Author(s):  
André C. Carpentier
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Dietary Fatty Acids ◽  
Nonesterified Fatty Acid ◽  
Adipose Tissue Fatty Acid ◽  
Tissue Fatty Acid

Insulin inhibits systemic nonesterified fatty acid (NEFA) flux to a greater degree than glucose or any other metabolite. This remarkable effect is mainly due to insulin-mediated inhibition of intracellular triglyceride (TG) lipolysis in adipose tissues and is essential to prevent diabetic ketoacidosis, but also to limit the potential lipotoxic effects of NEFA in lean tissues that contributes to the development of diabetes complications. Insulin also regulates adipose tissue fatty acid esterification, glycerol and TG synthesis, lipogenesis and possibly oxidation, contributing to the trapping of dietary fatty acids in the postprandial state. Excess NEFA flux at a given insulin level has been used to define in vivo adipose tissue insulin resistance. Adipose tissue insulin resistance defined in this fashion has been associated with several dysmetabolic features and complications of diabetes, but the mechanistic significance of this concept is not fully understood. This review focusses on the in vivo regulation of adipose tissue fatty acid metabolism by insulin and the mechanistic significance of the current definition of adipose tissue insulin resistance. One hundred years after the discovery of insulin and despite decades of investigations, much is still to be understood about the multifaceted in vivo actions of this hormone on adipose tissue fatty acid metabolism.

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.

Abstract 618: Dietary Omega-3 Fatty Acid Compete With Arachidonic Acid For The Formation Of Physiologically Active Cyp-eicosanoids In Man

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Anne Konkel ◽  
Robert Fischer ◽  
Heidrun Mehling ◽  
Petra Kast ◽  
Christoph Schroeder ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Fatty Acid ◽  
Dietary Fatty Acids ◽  
Omega 3 ◽  
Omega 3 Fatty Acid ◽  
Total Fatty Acids ◽  
Blood And Urine Samples ◽  
The Individual

Cytochrome P450 (CYP)-dependent metabolites of arachidonic acid (AA; 20:4 n-6) regulate vascular, renal, and cardiac function. However, the same CYP isoforms that metabolize AA also accept eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3) as alternative substrates, suggesting that the profile of physiologically active CYP-eicosanoids can be modulated in vivo by changing the dietary fatty acid composition. After we proved this hypothesis in rodents, we now expanded our studies to humans. The trial included 10 healthy men and 10 women aged 18 to 45 years (EudraCT: 2009-013458-33). They ingested 1 Omacor® capsule (480 mg EPA + 360 mg DHA) daily for the first 4 weeks, and two capsules daily in the subsequent 4 weeks, followed by 8 weeks of wash-out. Fatty acids and CYP-dependent metabolites were determined in blood and urine samples by gas chromatography and LC-MS/MS, respectively. The Omega-3 Index (% EPA + DHA of total fatty acids in red blood cells) increased from 4.98±0.80 to 8.03±1.06 at week 8 (p <0.001 vs. week 0), and declined to 6.33±1.44 at week 16. Concomitantly, the plasma CYP-epoxyeicosanoid index, defined as the ratio of EPA- plus DHA- vs. AA-derived epoxymetabolites ((EEQs+EDPs)/EETs), increased almost 3-fold from 0.83±0.05 to 2.35±0.17 (p <0.001; week 0 vs. week 8), and declined to 1.58±0.53 at week 16. In urine, the corresponding hydrolysis products were detectable and their ratio increased from 1.57±1.19 to 4.74±2.61 after 2g Omacor ® , and returned to baseline (1.38±0.75) after cessation of supplementation. Among the individual regioisomeric epoxymetabolites, AA-derived 14,15-EET predominated at baseline but was clearly exceeded by the EPA-derived 17,18-EEQ after EPA/DHA supplementation (3.24±0.26 vs.1.88±0.22 at week 0 and 2.96±0.24 vs. 6.15±0.43 ng/ml plasma at week 8). The plasma level of DHA-derived 19,20-EDP increased from 1.23±0.11 at week 0 to 2.52±0.19 at week 8. These results demonstrate that the human CYP-eicosanoid profile is highly susceptible to changes in dietary fatty acids. In particular, EPA/DHA supplementation promotes the formation of 17,18-EEQ that we previously identified as a candidate for mediating vasodilatory and antiarrhythmic effects of omega-3 fatty acids.

Lasting alterations of the sodium current by short-term hyperlipidemia as a mechanism for initiation of cardiac remodeling

2014 ◽  
Vol 306 (2) ◽  
pp. H291-H297 ◽  
Author(s):  
M. Biet ◽  
N. Morin ◽  
O. Benrezzak ◽  
F. Naimi ◽  
S. Bellanger ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Cardiac Remodeling ◽  
Sodium Current ◽  
Resting Membrane Potential ◽  
Short Term ◽  
Nonesterified Fatty Acids ◽  
Short Term Exposure

Clinical and animal studies indicate that increased fatty acid delivery to lean tissues induces cardiac electrical remodeling and alterations of cellular calcium homeostasis. Since this may represent a mechanism initiating cardiac dysfunction during establishment of insulin resistance and diabetes or anaerobic cardiac metabolism (ischemia), we sought to determine if short-term exposure to high plasma concentration of fatty acid in vivo was sufficient to alter the cardiac sodium current ( INa) in dog ventricular myocytes. Our results show that delivery of triglycerides and nonesterified fatty acids by infusion of Intralipid + heparin (IH) for 8 h increased the amplitude of INa by 43% and shifted its activation threshold by −5 mV, closer to the resting membrane potential. Steady-state inactivation (availability) of the channels was reduced by IH with no changes in recovery from inactivation. As a consequence, INa “window” current, a strong determinant of intracellular Na+ and Ca2+ concentrations, was significantly increased. The results indicate that increased circulating fatty acids alter INa gating in manners consistent with an increased cardiac excitability and augmentation of intracellular calcium. Moreover, these changes could still be measured after the dogs were left to recover for 12 h after IH perfusion, suggesting lasting changes in INa. Our results indicate that fatty acids rapidly induce cardiac remodeling and suggest that this process may be involved in the development of cardiac dysfunctions associated to insulin resistance and diabetes.

scholarly journals A longitudinal study of the antilipolytic effect of insulin in women following bariatric surgery

2021 ◽  
Author(s):  
Kelvin Ho Man Kwok ◽  
Daniel P. Andersson ◽  
Mikael Rydén ◽  
Peter Arner
Keyword(s):  
Insulin Resistance ◽  
Bariatric Surgery ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Glucose Utilization ◽  
Obese Women ◽  
Fatty Acid Utilization ◽  
Sensitivity Changes ◽  
Gastric By Pass

AbstractInsulin resistance of glucose utilization is fully restored following BMI normalization after bariatric surgery. We investigated if this also pertains to insulin-induced effects on fatty acid handling. Forty-three women with obesity (OB) were investigated before and 2 years after Roux-en-Y gastric by-pass when BMI was <30 kg/m2 (PO) and compared with 26 never obese women (NO). The Adipo-IR index was used as measure of insulin antilipolytic sensitivity. Changes (delta) in circulating glycerol and fatty acid levels during hyperinsulinemic euglycemic clamp represented the insulin maximum antilipolytic effect. Overall fatty acid utilization was reflected by delta fatty acids minus 3 × delta glycerol. Adipo-IR was higher in OB than in NO and PO (p < 0.0001), the latter two groups having similar values. Insulin lowered glycerol levels by about 70% in all groups, but delta glycerol was 30% larger in PO than in NO (p = 0.04). Delta adds and adds utilization were similar in all groups. We conclude that women with obesity, whose BMI is normalized after bariatric surgery, have improved maximum in vivo antilipolytic effect of insulin above expected in absolute but not relative terms as regards glycerol changes, while the handling of circulating fatty acids is changed to the normal state.

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 Effect of Dietary Fat Composition and 2’Fucosyllactose on Neonatal Piglet Growth and Organ Lipid Composition

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1038-1038
Author(s):  
Michael Miklus ◽  
Pedro Prieto ◽  
Cynthia Barber ◽  
Robert Rhoads ◽  
Samer El-Kadi
Keyword(s):  
Fatty Acids ◽  
Body Weight ◽  
Fatty Acid ◽  
Body Weight Gain ◽  
Dietary Fatty Acids ◽  
The Body ◽  
The Other ◽  
Human Infant ◽  
Lps Challenge ◽  
Group 3

Abstract Objectives The objectives of this study were to determine the effect of 2’fucosyllactose (2’FL) and fat blends on growth, body composition and fatty acid profile of the liver and brain using the neonatal pig as a model for the human infant. Methods Pigs (3 d old) were randomly assigned to either: 1. control, 2. Palm Olein (PO) fat blend – Low 2'-FL, 3. PO – High 2'-FL, 4. High oleic acid (HO) – Low 2'-FL, 5. HO FB – High 2'-FL, 6. PO FB – GLA, or 7. kept with their sows. Pigs in groups 1 to 6 received 250 ml·kg−1·d−1 of formula in 5 equal meals for 15 d. On day 14 of the study, groups 1–6 received intraperitoneal E. coli LPS challenge at 100 µg·kg−1 weight. Results Body weight was greater for piglets fed by sows than those in the other groups (P &lt; 0.001). In addition, % fat and bone mineral content were higher in the sow-fed group while lean % was less sow-fed piglets (group 7) compared with those in the other groups (P &lt; 0.05). Only longissimus weight expressed as a % of body weight, was greater for group 7 compared with all other groups (P &lt; 0.001). Soleus, semitendinosus, brain, heart and spleen weights as a % of body weight were similar across all groups. However, liver weight as a % of body weight was greater in groups 1–6 (3.7%) compared with group 7 (2.8%; P &lt; 0.001). The proportion of brain 16:1 fatty acid was less (0.83%) for groups 1–6 than for group 7 pigs (1.08%; P &lt; 0.0001). The proportion of 20:3 N6 was greatest (0.66%) for group 3 compared with groups 1 and 4 (0.55%; P &lt; 0.05). In addition, the proportion of 20:5 N3 was greatest (0.12%) for group 3 compared with groups 1 and 7 (0.07%; P &lt; 0.05). The proportion of liver 16:1, 18:0, and 18:1 cis-11 fatty acids were greater for group 7 (2.3, 23, 2.2%) than groups 1–6 (0.2, 20, 1.2%; P &lt; 0.0001). Conversely, the contribution of 14:0, 18:1 cis-9, 18:3 N6 cis-6,9,12, and 22:6 N3 were greater for pigs in groups 1–6 (1.3, 0.6, and 14, 7.8%) compared with those in group 7 (0.5, 8.5, 0.2 and 3.5%; P &lt; 0.0001). Conclusions Our data suggest that feeding 2’fucosyllactose had no effect on the body weight gain and composition in neonatal pigs. Our data also suggest that dietary fatty acids have a greater effect on liver than on brain fatty acid composition. Funding Sources Funding for the work was provided by Perrigo Nutritionals, LLC.

scholarly journals Interaction of physical activity and diet: implications for insulin-glucose dynamics

1999 ◽  
Vol 2 (3a) ◽  
pp. 363-368 ◽  
Author(s):  
Jean-Jacques Grimm
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Risk ◽  
Fatty Acid ◽  
Glycogen Synthase ◽  
Insulin Resistance Syndrome ◽  
Low Fat ◽  
Exercise Interventions ◽  
High Carbohydrate ◽  
Fat Diets

AbstractIn Western countries 25–35% of the population have insulin resistance syndrome characteristics.The defects most likely to explain the insulin resistance of the insulin resistance syndrome include: 1) the glucose transport system of skeletal muscle (GLUT-4) and its different signalling proteins and enzymes; 2) glucose phosphorylation by hexokinase; 3) glycogen synthase activity and 4) competition between glucose and fatty acid oxidation (glucose-fatty acid cycle).High carbohydrate/low fat diets deteriorate insulin sensitivity on the short term. Howewer, on the long term, high fat/low carbohydrate diets have a lower satiating power, induce low leptin levels and eventually lead to higher energy consumption, obesity and more insulin resistance. Moderately high-carbohydrate (45–55% of the daily calories)/low-fat diets seem to be a good choice with regard to the prevention of diabetes and cardiovascular risk factors as far as the carbohydrates are rich in fibers.Long-term interventions with regular exercise programs show a 1/3 decrease in the appearance of overt diabetes in glucose intolerant subjects. Furthermore, diet and exercise interventions "normalise" the mortality rate of patients with impared glucose tolerance.Therefore, moderately high carbohydrate/low fat diets are most likely to prevent obesity and type 2 diabetes. Triglycerides should be monitored and, in some cases, a part of the carbohydrates could be replaced by fat rich in monounsaturated fatty acids. However, total caloric intake is of utmost importance, as weight gain is the major determinant for the onset of insulin resistance and glucose intolerance.Regular (when possible daily) exercise, decreases cardiovascular risk. With regard to insulin resistance, resistance training seems to offer some advantages over aerobic endurance activities.

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