scholarly journals Unique plasma metabolite signature for adolescents with Klinefelter syndrome reveals altered fatty acid metabolism

2021 ◽  
Author(s):  
Shanlee Davis ◽  
Rhianna Urban ◽  
Angelo D'Alessandro ◽  
Julie A Reisz ◽  
Christine L Chan ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Molecular Mechanisms ◽  
Klinefelter Syndrome ◽  
Pubertal Development ◽  
Saturated Fatty Acids ◽  
Adolescent Males ◽  
Enrichment Ratio ◽  
Plasma Metabolites ◽  
Pubertal Stage ◽  
Plasma Metabolome

Conditions related to cardiometabolic disease, including metabolic syndrome and type 2 diabetes, are common among men with Klinefelter syndrome (KS). The molecular mechanisms underlying this aberrant metabolism in KS are largely unknown, although there is an assumption that chronic testosterone deficiency plays a role. This cross-sectional study compared plasma metabolites in 31 pubertal adolescent males with KS to 32 controls of similar age (14 ± 2 yrs), pubertal stage, and body mass index z-score (0.1 ± 1.2), and then between testosterone treated (n=16) and untreated males with KS. The plasma metabolome in males with KS was distinctly different from controls, with 22% of measured metabolites having a differential abundance and seven metabolites nearly completely separating KS from controls (AUC>0.9, p<0.0001). Multiple saturated free fatty acids were higher in KS while mono- and polyunsaturated fatty acids were lower, and the top significantly enriched pathway was mitochondrial β-oxidation of long-chain saturated fatty acids (enrichment ratio 16, p<0.0001). In contrast, there were no observed differences in metabolite concentrations between testosterone-treated and untreated individuals with KS. In conclusion, the plasma metabolome profile in adolescent males with KS is distinctly different from males without KS independent of age, obesity, pubertal development, or testosterone treatment status, and is suggestive of differences in mitochondrial β-oxidation.

scholarly journals Pinto Beans (Phaseolus vulgaris L.) Lower Non-HDL Cholesterol in Hamsters Fed a Diet Rich in Saturated Fat and Act on Genes Involved in Cholesterol Homeostasis

2019 ◽  
Vol 149 (6) ◽  
pp. 996-1003 ◽  
Author(s):  
An Tien Nguyen ◽  
Sami Althwab ◽  
Haowen Qiu ◽  
Richard Zbasnik ◽  
Carlos Urrea ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Saturated Fatty Acids ◽  
Saturated Fat ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Liver Cholesterol ◽  
Intestinal Cholesterol Absorption ◽  
Pinto Beans

ABSTRACT Background Pinto beans contain multiple active agents such as polyphenols, flavonoids, and saponins, and have been shown to lower cholesterol, but the mechanisms involved in this effect have not been explored. Objective This study was to investigate the changes in cholesterol metabolism in response to whole pinto beans (wPB) and their hulls (hPB) supplemented into a diet rich in saturated fat and the molecular mechanisms potentially responsible for these effects in hamsters. Methods Forty-four 9-wk-old male Golden Syrian hamsters were randomly assigned to 4 diet groups (n = 11), including a 5% (wt:wt) fat diet [normal-fat diet (NF)], a 15% (wt:wt) fat diet [diet rich in saturated fat (HSF), saturated fatty acids accounted for 70% of total fatty acids], or HSF supplemented with 5% (wt:wt) wPB or 0.5% (wt:wt) hPB for 4 wk. Plasma, liver, intestinal, and fecal samples were collected to evaluate multiple cholesterol markers and gene targets. Results The plasma non-high-density lipoprotein (non-HDL) concentration was significantly reduced in the wPB- and hPB-supplemented groups by 31.9 ± 3.5% and 53.6 ± 3.2%, respectively, compared with the HSF group (P < 0.01), to concentrations comparable with the NF group. The wPB-supplemented hamsters had significantly lower liver cholesterol (45.1%, P < 0.001) and higher fecal cholesterol concentrations (94.8%, P = 0.001) than those fed the HSF. The expressions of hepatic 3-hydroxy-3-methylglutaryl CoA reductase (Hmgcr) and small intestinal acyl-coenzyme A: cholesterol acyltransferase 2 (Acat2) were significantly decreased in animals administered wPB (by 89.1% and 63.8%, respectively) and hPB (by 72.9% and 47.7%, respectively) compared with their HSF-fed counterparts (P < 0.05). The wPB normalized the expression of Acat2 to the level of the NF group. Conclusion Pinto beans remediated high cholesterol induced by HSF in male hamsters by decreasing hepatic cholesterol synthesis and intestinal cholesterol absorption, effects which were partially exerted by the hulls.

scholarly journals Time-Restricted Feeding a High-fat Diet in Mice Elevates Plasma Concentration of Saturated Fatty Acids but Reduces Concentrations of Multiple Amino Acids (OR27-02-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Bret Rust ◽  
Aaron Mehus ◽  
Joseph Idso ◽  
Matthew Picklo
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Energy Expenditure ◽  
Control Diet ◽  
Saturated Fatty Acids ◽  
Plasma Metabolites ◽  
Dark Phase ◽  
Restricted Feeding ◽  
High Fat ◽  
Branched Chain

Abstract Objectives Obesity and obesity-related disease contribute to health care costs and pose serious health risks. Rodent studies indicate that time-restricted feeding (TRF) may be effective in reducing adiposity and metabolic disease associated with obesity. However, the metabolic pathways impacted by TRF in the context of obesogenic, high-fat (HF) diets need clarity. In the present work we examined the metabolomic changes in plasma induced by TRF of a HF diet in mice compared to a HF diet eaten ad libitum (AL) vs AL intake of a low-fat (LF) control diet. Methods Male mice (12 weeks old) were fed a LF-AL diet (16%en fat), a HF-AL diet (48%en fat) or a HF diet restricted to feeding for 12 hours per day during the dark phase (HF-TRF). In week 9 of the study, energy expenditure data were collected. After 12 weeks, animals were fasted and plasma collected for clinical chemistries and metabolomic analysis. Multivariate analysis was used to discriminate diet treatments in untargeted metabolomic data. Results Energy expenditure measurements throughout the day showed a markedly reduced fasting respiratory exchange ratio (RER) in HF-TRF mice during the inactive (light) phase compared to AL groups. Measures of insulin resistance, while increased with HF-AL intake, were resolved in the HF-TRF group. Partial least squares discriminant analysis revealed plasma non-esterified fatty acids (NEFA) and amino acids (AA) to be important discriminators between diet treatments. TRF resulted in elevated NEFA concentrations of the saturated fatty acids (12:0 to 18:0) and the polyunsaturated fatty acids α-linolenic acid and linoleic acid compared to HF-AL. Conversely, the concentrations of aromatic and branched chain amino acids were reduced in HF-TRF mice compared to HF-AL mice. Conclusions Alterations in plasma metabolites following TRF of a HF diet are consistent with greater lipid utilization during the inactive phase as reflected in the RER. Decreases in the aromatic and branched chain amino acid concentrations are consistent with improved insulin sensitivity in humans. Funding Sources This work was supported by USDA-ARS project 3062-51000-053-00D. Supporting Tables, Images and/or Graphs

scholarly journals Potential relationship between dietary long-chain saturated fatty acids and hypothalamic dysfunction in obesity

2019 ◽  
Author(s):  
Domenico Sergi ◽  
Lynda M Williams
Keyword(s):  
Fatty Acids ◽  
Molecular Mechanisms ◽  
Saturated Fatty Acids ◽  
Current Evidence ◽  
Hypothalamic Dysfunction ◽  
Lipid Species ◽  
Hypothalamic Inflammation ◽  
Dietary Component ◽  
Refined Carbohydrates ◽  
Long Chain

Abstract Diet-induced hypothalamic inflammation, which leads to hypothalamic dysfunction and a loss of regulation of energy balance, is emerging as a potential driver of obesity. Excessive intake of long-chain saturated fatty acids is held to be the causative dietary component in hypothalamic inflammation. This review summarizes current evidence on the role of long-chain saturated fatty acids in promoting hypothalamic inflammation and the related induction of central insulin and leptin insensitivity. Particularly, the present review focuses on the molecular mechanisms linking long-chain saturated fatty acids and hypothalamic inflammation, emphasizing the metabolic fate of fatty acids and the resulting lipotoxicity, which is a key driver of hypothalamic dysfunction. In conclusion, long-chain saturated fatty acids are key nutrients that promote hypothalamic inflammation and dysfunction by fostering the build-up of lipotoxic lipid species, such as ceramide. Furthermore, when long-chain saturated fatty acids are consumed in combination with high levels of refined carbohydrates, the proinflammatory effects are exacerbated via a mechanism that relies on the formation of advanced glycation end products.

scholarly journals Mechanisms of Action of trans Fatty Acids

2019 ◽  
Vol 11 (3) ◽  
pp. 697-708 ◽  
Author(s):  
Antwi-Boasiako Oteng ◽  
Sander Kersten
Keyword(s):  
Fatty Acids ◽  
Er Stress ◽  
Trans Fatty Acids ◽  
Cholesterol Synthesis ◽  
Molecular Mechanisms ◽  
Unsaturated Fatty Acids ◽  
Regulatory Element ◽  
Saturated Fatty Acids ◽  
Mechanisms Of Action ◽  
Plasma Lipoproteins

ABSTRACT Human studies have established a positive association between the intake of industrial trans fatty acids and the development of cardiovascular diseases, leading several countries to enact laws that restrict the presence of industrial trans fatty acids in food products. However, trans fatty acids cannot be completely eliminated from the human diet since they are also naturally present in meat and dairy products of ruminant animals. Moreover, bans on industrial trans fatty acids have not yet been instituted in all countries. The epidemiological evidence against trans fatty acids by far overshadows mechanistic insights that may explain how trans fatty acids achieve their damaging effects. This review focuses on the mechanisms that underlie the deleterious effects of trans fatty acids by juxtaposing effects of trans fatty acids against those of cis-unsaturated fatty acids and saturated fatty acids (SFAs). This review also carefully explores the argument that ruminant trans fatty acids have differential effects from industrial trans fatty acids. Overall, in vivo and in vitro studies demonstrate that industrial trans fatty acids promote inflammation and endoplasmic reticulum (ER) stress, although to a lesser degree than SFAs, whereas cis-unsaturated fatty acids are protective against ER stress and inflammation. Additionally, industrial trans fatty acids promote fat storage in the liver at the expense of adipose tissue compared with cis-unsaturated fatty acids and SFAs. In cultured hepatocytes and adipocytes, industrial trans fatty acids, but not cis-unsaturated fatty acids or SFAs, stimulate the cholesterol synthesis pathway by activating sterol regulatory element binding protein (SREBP) 2–mediated gene regulation. Interestingly, although industrial and ruminant trans fatty acids show similar effects on human plasma lipoproteins, in preclinical models, only industrial trans fatty acids promote inflammation, ER stress, and cholesterol synthesis. Overall, clearer insight into the molecular mechanisms of action of trans fatty acids may create new therapeutic windows for the treatment of diseases characterized by disrupted lipid metabolism.

scholarly journals Modulation of Fatty Acid-Related Genes in the Response of H9c2 Cardiac Cells to Palmitate and n-3 Polyunsaturated Fatty Acids

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 537
Author(s):  
Silvia Cetrullo ◽  
Stefania D’Adamo ◽  
Veronica Panichi ◽  
Rosa Maria Borzì ◽  
Carla Pignatti ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Molecular Mechanisms ◽  
Dietary Habits ◽  
Regulatory Element ◽  
Saturated Fatty Acids ◽  
Cardiac Cells ◽  
High Dose ◽  
Mrna Levels

While high levels of saturated fatty acids are associated with impairment of cardiovascular functions, n-3 polyunsaturated fatty acids (PUFAs) have been shown to exert protective effects. However the molecular mechanisms underlying this evidence are not completely understood. In the present study we have used rat H9c2 ventricular cardiomyoblasts as a cellular model of lipotoxicity to highlight the effects of palmitate, a saturated fatty acid, on genetic and epigenetic modulation of fatty acid metabolism and fate, and the ability of PUFAs, eicosapentaenoic acid, and docosahexaenoic acid, to contrast the actions that may contribute to cardiac dysfunction and remodeling. Treatment with a high dose of palmitate provoked mitochondrial depolarization, apoptosis, and hypertrophy of cardiomyoblasts. Palmitate also enhanced the mRNA levels of sterol regulatory element-binding proteins (SREBPs), a family of master transcription factors for lipogenesis, and it favored the expression of genes encoding key enzymes that metabolically activate palmitate and commit it to biosynthetic pathways. Moreover, miR-33a, a highly conserved microRNA embedded in an intronic sequence of the SREBP2 gene, was co-expressed with the SREBP2 messenger, while its target carnitine palmitoyltransferase-1b was down-regulated. Manipulation of the levels of miR-33a and SREBPs allowed us to understand their involvement in cell death and hypertrophy. The simultaneous addition of PUFAs prevented the effects of palmitate and protected H9c2 cells. These results may have implications for the control of cardiac metabolism and dysfunction, particularly in relation to dietary habits and the quality of fatty acid intake.

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.

scholarly journals Partial replacement of soybean meal by white lupine seeds in the diet of dairy cows

2020 ◽  
Vol 33 (6) ◽  
pp. 957-964 ◽  
Author(s):  
Miroslav Joch ◽  
Václav Kudrna
Keyword(s):  
Fatty Acids ◽  
Dairy Cows ◽  
Soybean Meal ◽  
Feed Efficiency ◽  
Milk Fat ◽  
Saturated Fatty Acids ◽  
Latin Square ◽  
Partial Replacement ◽  
Plasma Metabolites ◽  
White Lupine

Objective: An experiment was conducted to determine the effect of partial replacement of soybean meal (SBM) by white lupine seeds (WLS) on milk yield and quality, feed efficiency and rumen fermentation of high-yielding dairy cows.Methods: Thirty multiparous cows of two breeds (20 Holstein and 10 Czech Pied cows) in early mid-lactation received three diets (treatments) in a 3×3 Latin square design with a 28-d period. The dietary treatments were as follows: CON (control total mixed ration with SBM, no WLS), WLS30 (30% of the SBM was replaced, on a dry matter basis, by WLS), and WLS50 (50% of the SBM was replaced by WLS).Results: Feed intake by the cows was not affected (p = 0.331) by the diets. Milk production decreased with increasing proportions of WLS in the diet. Cows fed WLS50 yielded approximately 1 kg/d (p<0.001) less milk than cows fed the CON diet. The proportions of milk fat (p = 0.640), protein (p = 0.507), and lactose (p = 0.709) were not altered by the diet. For milk fat, feeding with WLS50 reduced the proportion of total saturated fatty acids (p<0.001) and increased the proportion of total monounsaturated fatty acids (p<0.001), mainly through oleic acid (p<0.001). No differences were found in feed efficiency, body weight, and blood plasma metabolites between groups. Rumen ammonia-N levels tended (p = 0.087) to increase with increasing proportions of WLS in the diet, whereas no effect of diet on rumen pH was found (p = 0.558).Conclusion: We did not identify the safe range within which raw WLS can efficiently replace SBM in the diet of high-producing dairy cows. In contrast, even partial replacement of SBM by WLS favorably changed the milk fatty acid profile.

scholarly journals Effect of Different Types of Dietary Fatty Acids on Subclinical Inflammation in Humans

2013 ◽  
pp. 145-152 ◽  
Author(s):  
I. KRÁLOVÁ LESNÁ ◽  
P. SUCHÁNEK ◽  
E. BRABCOVÁ ◽  
J. KOVÁŘ ◽  
H. MALÍNSKÁ ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Systemic Inflammation ◽  
Molecular Mechanisms ◽  
Statistical Significance ◽  
Saturated Fatty Acids ◽  
Dietary Fatty Acids ◽  
Low Density ◽  
Pufa Diet

Replacing SAFAs (saturated fatty acids) for vegetable PUFAs (polyunsaturated fatty acids) has a well documented positive effect on the lipoprotein pattern while the direct effect of dietary fatty acids composition on systemic inflammation remains to be proven. In well controlled randomised cross-over study with 15 overweight/obese postmenopausal women, the effect of dietary switch on systemic inflammation was investigated. A two 3 weeks dietary period either with predominant animal fat (SAFA, 29 caloric % SAFA) or vegetable fat (PUFA 25 % caloric % PUFA) were interrupted by wash-out period. The expected increasing effect on SAFA diet to LDL-C (low density cholesterol) and opposite effect of PUFA diet was documented following changes in fatty acid spectrum in VLDL (very low density cholesterol) particles. The switch from SAFA diet to PUFA diet produced a significant change of CRP (C-reactive protein) concentration (p<0.01) whereas similar trend of IL-18 did not reach statistical significance. In this study, previous in vitro results of different SAFA and PUFA proinflammatory effects with well documented molecular mechanisms were first proven in a clinical study. It could be stated that the substantial change of dietary fatty acid composition might influence proinflammatory effect in addition to traditional cardiovascular risk factors.

scholarly journals Functional Active Genomics of Isoprene Biogenesis and resistance to cardiovascular diseases

2021 ◽  
Vol 2 (4) ◽  
pp. 73-78
Author(s):  
Anna Fedoriv ◽  
Ivan Fedoriv
Keyword(s):  
Fatty Acids ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Saturated Fatty Acids ◽  
Research Work ◽  
Energy Parameter ◽  
Chronic Inflammatory Disease ◽  
Early Stages ◽  
Atherosclerosis Development ◽  
Atherosclerotic Process

The pathologic development of the atherosclerotic process is often associated with the metabolism of saturated and unsaturated fatty acid. Substitution of the saturated fatty acids in nutrition for polyunsaturated fatty acids is traditionally associated with the lowering of risk of coronary breaches rise. Understanding the molecular mechanisms of the atherosclerosis development and progress is very important for early diagnostic and effective medical treatment of the above-mentioned disease. After a thorough analysis of the data available on the pathological atherosclerotic process, we have come to the conclusion that this disease begins from vascular smooth muscle cell (VSMC) impaired function. In the basis of the atherosclerosis development lies isoprenes biogenesis breach, caused by cholesterol and the products of its metabolism. Atherosclerosis is a chronic inflammatory disease of the media wall of large- and medium-sized arteries. And endothelium injury is a consequence of the pathologic process progressing in myocytes. Metabolic problems have become so relevant that it is time to form a metabolic policy. Real target programs for the prevention of the development of metabolic diseases and their diagnostics in the early stages of development should be developed. But in order to achieve this goal, it is necessary to know the real molecular mechanism of development of the early stages of metabolic diseases. It is necessary to recognize that the research work on the metabolic problem was carried out mainly in the plane of the functionally-energy parameter and captures only the consequences of the pathological process. And the very reason and early stages of metabolic diseases remained hidden from us, as they are depending on the pathology in the plane Regulatory, Information, Coordination and Functional active bioenergy system.

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