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 ◽  
...  

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.

2010 ◽  
Vol 298 (6) ◽  
pp. E1122-E1130 ◽  
Author(s):  
Sun Ju Choi ◽  
Francis Kim ◽  
Michael W. Schwartz ◽  
Brent E. Wisse

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.


2015 ◽  
Vol 100 (10) ◽  
pp. 3760-3769 ◽  
Author(s):  
Maike Wolters ◽  
Heike Schlenz ◽  
Claudia Börnhorst ◽  
Patrizia Risé ◽  
Claudio Galli ◽  
...  

Context: Activity of delta-9, delta-6, and delta-5 desaturases (D9D, D6D, D5D) are associated with obesity, insulin resistance, and dyslipidemia. Objective: To investigate the association of estimated desaturase activities with weight status, insulin resistance, and dyslipidemia in children, cross-sectionally and longitudinally. Design: The IDEFICS (Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants) cohort study was used, with examinations at baseline (T0) and after 2 years (T1). Setting and Participants: Children aged 2 to less than 10 years from eight European countries were recruited in kindergartens/primary schools. Children with available data on fatty acids, outcome, and covariate information were included in the analyses. Methods: Whole blood fatty acids were analyzed in 2600 children at baseline. D9D (16:1n-7/16:0), D6D (20:3n-6/18:2n-6), and D5D (20:4n-6/20:3n-6) activities were estimated from product-precursor fatty acids ratios. Body mass index (BMI), Homeostatic Model Assessment index, and high-density lipoprotein cholesterol (HDL), and triglycerides (TG) served as outcomes for weight status, insulin resistance, and dyslipidemia, respectively. Linear and logistic regression and repeated measures models were used to assess the cross-sectional and longitudinal associations between desaturase activity and outcomes. Results: In the cross-sectional analysis, D9D and D6D were positively associated with BMI and TG z-scores and inversely with HDL z-scores. D5D was inversely associated with BMI and TG z-scores (ie, a D5D increase of 1 unit is associated with a BMI z-score decrease of 0.07 and a 28% lower odds ratio for TG ≥75th percentile). Longitudinally, similar associations were found for T0 desaturase activities with BMI and for T0 D6D with HDL at follow-up (T1). Baseline D6D and D5D were positively associated with the change of HDL z-score from T0 to T1, and D6D with the change of Homeostatic Model Assessment index z-score. Conclusion: Desaturase activities are associated with metabolic risk markers already in young children and appear to predict the metabolic risk.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Takashi Muramatsu ◽  
Hiroshi Yatsuya ◽  
Kunihiro Matsushita ◽  
Hirotsugu Mitsuhashi ◽  
Hideaki Toyoshima ◽  
...  

Background: Asians including Japanese are more susceptible to glucose intolerance or type 2 diabetes mellitus (DM) than Caucasians. However little is known about the effects of dietary fatty acid (FA) intake on insulin resistance (IR) in Japanese. Objective: Our aim was to investigate associations between IR and habitual dietary intake of FAs among middle-aged Japanese adults. Methods: We designed a cross-sectional survey of 3383 Japanese adults aged 35– 66 years. IR was measured with homeostasis model assessment (HOMA-R) and nutrient intake was estimated by a self-administered diet history questionnaire. All amounts of nutrients were energy-adjusted as the residuals from regression model. Results: Log-transformed HOMA-R had a significant negative correlation with polyunsaturated fatty acid (PUFA). Multivariate-adjusted regression analysis demonstrated that IR had a significant positive association with saturated fatty acid (SFA) and inverse associations with n-6 series PUFA independently of age, sex, BMI, lipid profiles, other macronutrients and lifestyle. Multivariate-adjusted odds ratios of IR, defined as a top quartile of HOMA-R distribution, across the quartiles of energy-adjusted intakes were 1.0, 0.89, 0.73 and 0.57 for linoleic acid ( P for trend = 0.007) and 1.0, 0.90, 0.68 and 0.61 for alpha-linolenic acid ( P for trend = 0.010), respectively. Marine-derived n-3 PUFA and the ratio of n-6 to n-3 PUFA had no consistent association with IR. Conclusions: Our cross-sectional data suggest that a modification of dietary fat intake to substitute PUFA, in particular linoleic acid and alpha-linolenic acid, for SFA may have a clinical efficacy to prevent IR among a Japanese population.


Author(s):  
Martin Benzler ◽  
Jonas Benzler ◽  
Sigrid Stoehr ◽  
Cindy Hempp ◽  
Mohammed Z. Rizwan ◽  
...  

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.


2013 ◽  
Vol 305 (4) ◽  
pp. E549-E556 ◽  
Author(s):  
Vidya Gadang ◽  
Rohit Kohli ◽  
Andriy Myronovych ◽  
David Y. Hui ◽  
Diego Perez-Tilve ◽  
...  

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.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A421-A421
Author(s):  
John N Falcone ◽  
Maurice A Hurd ◽  
Sonal Kumar ◽  
Michele Yeung ◽  
Carolyn Newberry ◽  
...  

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.


2009 ◽  
Vol 102 (6) ◽  
pp. 888-894 ◽  
Author(s):  
Yuan E. Zhou ◽  
Stan Kubow ◽  
Eric Dewailly ◽  
Pierre Julien ◽  
Grace M. Egeland

Emerging evidence shows that desaturase 5 (Δ5), the key regulator in the synthesis of highly unsaturated long-chain fatty acids (HUFA), is modulated by factors including adiposity, diet and insulin resistance. We explored the association of these factors in a cross-sectional study within a high-risk Cree population. Anthropometric measures and fasting blood glucose and insulin were analysed. Δ5 was estimated as the 20 : 4n-6:20 : 3n-6 ratio in erythrocyte membranes. The setting of the present study was the Mistissini community in the Cree Territory of Québec, Canada with ninety-eight female and sixty-eight male subjects aged 20–88 years. Obesity (BMI ≥ 30 kg/m2) was prevalent across age groups. Δ5 was inversely associated with BMI (Spearman's correlation coefficient (rs) − 0·175;P = 0·03) and positively associated with age (rs0·593;P < 0·0001), which was driven by age-related increases in dietary intake ofn-3 fatty acids and decreases in 20 : 3n-6. Homeostasis model assessment of insulin resistance (HOMA-IR) was significantly inversely associated with Δ5 in age-adjusted linear regression analyses in normoglycaemic individuals (β − 2·110 (se0·566);P < 0·001), whereas no association was observed among glucose-intolerant individuals (interaction termP = 0·03). In contrast, there were no significant interactions indicating differences in the slope for each of the adiposity measures in their associations with Δ5. The present study indicates that the dietary transition of reduced consumption of fish among younger Cree may compound the effects of obesity and emerging insulin resistance which, in turn, could reduce bioavailability of HUFAn-3 (through reduced Δ5 activity). Also, the study suggests that disease progression is an important consideration when evaluating correlates of Δ5 activity in observational studies.


2015 ◽  
Vol 27 (4) ◽  
pp. 593 ◽  
Author(s):  
Tawiwan Pantasri ◽  
Linda L. Wu ◽  
M. Louise Hull ◽  
Thomas R. Sullivan ◽  
Michael Barry ◽  
...  

Obesity is associated with decreased pregnancy rates due, in part, to compromised oocyte quality. The aim of the present cross-sectional study of 84 women undergoing oocyte aspiration was to: (1) compare insulin, lipids and glucose in follicular fluid with serum; (2) determine whether increased body mass index (BMI) and waist circumference, hyperinsulinaemia, dyslipidaemia or metabolic syndrome altered follicular fluid metabolites; and (3) determine relative lipid content in oocytes to reveal any influence of these parameters on oocyte quality and IVF outcomes. Insulin, glucose, triglyceride and free fatty acids were lower in follicular fluid than blood and not strictly correlated between compartments. Insulin, glucose and triglyceride positively correlated with increasing BMI and waist circumference in blood and follicular fluid. Insulin increased in follicular fluid in association with metabolic syndrome. Free fatty acid composition analysis showed saturated fatty acids, particularly palmitic and stearic acid, to be more prevalent in follicular fluid than blood. There were no associations between follicular fluid metabolites or oocyte lipid content and clinical outcomes; however, oocyte immaturity correlated with follicular fluid glucose and fatty acid levels, as well as metabolic syndrome. The present study confirms that the human ovarian follicular environment surrounding the oocyte exhibits a unique metabolite profile compared with blood, with distinct localisation of lipids within follicular fluid and oocytes.


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