AdipoR2 is Essential for Membrane Lipid Homeostasis in Response to Dietary Saturated Fats

ABSTRACTMembrane lipid composition influences vital processes in all types of cells. The mechanisms by which cells maintain membrane lipid homeostasis while obtaining most of their constituent fatty acids from a varied diet remain largely unknown. In an attempt to discover such mechanisms, we performed an unbiased forward genetic screen in Caenorhabditis elegans and conclude that the adiponectin receptor 2 (AdipoR2) pathway is essential to prevent saturated fat-mediated cellular toxicity. Transcriptomics, lipidomics and membrane property analyses in human HEK293 cells and primary human endothelial cells further support our conclusion that the essential function of AdipoR2 is to respond to membrane rigidification by promoting fatty acid desaturation. Our results demonstrate that AdipoR2-dependent regulation of membrane homeostasis is a fundamental mechanism conserved from nematodes to mammals that prevents saturated fat-mediated lipotoxicity.ONE SENTENCE SUMMARYThe AdipoR2 protein insures membrane homeostasis in response to dietary saturated fatty acids that promote membrane rigidification.

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Palmitic acid promotes resistin-induced insulin resistance and inflammation in SH-SY5Y human neuroblastoma

Scientific Reports ◽

10.1038/s41598-021-85018-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hamza Amine ◽

Yacir Benomar ◽

Mohammed Taouis

Keyword(s):

Insulin Resistance ◽

Fatty Acids ◽

Palmitic Acid ◽

Lipid Rafts ◽

Acid Treatment ◽

Protective Action ◽

Saturated Fatty Acids ◽

Membrane Lipid ◽

Human Neuroblastoma ◽

Peripheral Tissues

AbstractSaturated fatty acids such as palmitic acid promote inflammation and insulin resistance in peripheral tissues, contrasting with the protective action of polyunsaturated fatty acids such docosahexaenoic acid. Palmitic acid effects have been in part attributed to its potential action through Toll-like receptor 4. Beside, resistin, an adipokine, also promotes inflammation and insulin resistance via TLR4. In the brain, palmitic acid and resistin trigger neuroinflammation and insulin resistance, but their link at the neuronal level is unknown. Using human SH-SY5Yneuroblastoma cell line we show that palmitic acid treatment impaired insulin-dependent Akt and Erk phosphorylation whereas DHA preserved insulin action. Palmitic acid up-regulated TLR4 as well as pro-inflammatory cytokines IL6 and TNFα contrasting with DHA effect. Similarly to palmitic acid, resistin treatment induced the up-regulation of IL6 and TNFα as well as NFκB activation. Importantly, palmitic acid potentiated the resistin-dependent NFkB activation whereas DHA abolished it. The recruitment of TLR4 to membrane lipid rafts was increased by palmitic acid treatment; this is concomitant with the augmentation of resistin-induced TLR4/MYD88/TIRAP complex formation mandatory for TLR4 signaling. In conclusion, palmitic acid increased TLR4 expression promoting resistin signaling through TLR4 up-regulation and its recruitment to membrane lipid rafts.

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Manipulation of the fatty acids composition of poultry meat and giblets by dietary inclusion of two oil sources and conjugated linoleic acid

Arquivo Brasileiro de Medicina Veterinária e Zootecnia ◽

10.1590/s0102-09352008000600013 ◽

2008 ◽

Vol 60 (6) ◽

pp. 1388-1398 ◽

Cited By ~ 3

Author(s):

S.F. Zanini ◽

E. Vicente ◽

G.L. Colnago ◽

B.M.S. Pessotti ◽

M.A. Silva

Keyword(s):

Fatty Acids ◽

Linoleic Acid ◽

Conjugated Linoleic Acid ◽

Canola Oil ◽

Broiler Chickens ◽

Saturated Fatty Acids ◽

Saturated Fat ◽

Monounsaturated Fatty Acids ◽

Poultry Meat ◽

Breast Meat

The effect of dietary conjugated linoleic acid (CLA) in association with two vegetable oil sources on the fatty acids of meat and giblets of broiler chickens was evaluated. Two hundred 21-day-old broiler chickens were distributed in a completely randomized factorial design 2 x 5 (two oil sources, soybean or canola oil; and five levels of CLA, 0.0, 2.5, 5.0, 7.5, and 10.0g/kg). The addition of CLA to the diet resulted in an increase (P<0.05) in CLA deposition in the analyzed tissues. CLA supplementation also reduced (P<0.05) the rate of polyunsaturated to saturated fatty acids in thigh, breast, heart, and gizzard. There was interaction of CLA x oil source (P<0.05). The intake of soybean oil, associated with increasing CLA, resulted in an increase in lipid deposition in edible portions as observed by an increase in the overall content of fatty acids, including CLA, while the use of canola oil, associated with increasing CLA in the diet, resulted in a decrease in lipid content in edible portions, specifically regarding that of saturated fat (P<0.05) in breast meat and liver and in the content of monounsaturated fatty acids (P<0.05) in thigh, breast, liver, and gizzard.

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Dairy Fat Consumption and the Risk of Metabolic Syndrome: An Examination of the Saturated Fatty Acids in Dairy

Nutrients ◽

10.3390/nu11092200 ◽

2019 ◽

Vol 11 (9) ◽

pp. 2200 ◽

Cited By ~ 8

Author(s):

Unger ◽

Torres-Gonzalez ◽

Kraft

Keyword(s):

Metabolic Syndrome ◽

Fatty Acids ◽

Disease Risk ◽

Saturated Fatty Acids ◽

Saturated Fat ◽

Dietary Guidelines ◽

The Body ◽

Specific Chemical ◽

Dairy Consumption ◽

The Impact

Lifestyle is a key modifiable risk factor involved in the manifestation of metabolic syndrome and, in particular, diet plays a pivotal role in its prevention and development. Current dietary guidelines discourage the consumption of saturated fat and dietary sources rich in saturated fat, such as dairy products, despite data suggesting that full-fat dairy consumption is protective against metabolic syndrome. This narrative review assessed the recent epidemiological and clinical research that examined the consumption of dairy-derived saturated fatty acids (SFA) on metabolic syndrome risk. In addition, this review evaluated studies of individual SFA to gain insight into the potential mechanisms at play with intake of a diet enriched with these dairy-derived fatty acids. This work underscores that SFA are a heterogenous class of fatty acids that can differ considerably in their biological activity within the body depending on their length and specific chemical structure. In summary, previous work on the impact of dairy-derived SFA consumption on disease risk suggests that there is currently insufficient evidence to support current dietary guidelines which consolidate all dietary SFA into a single group of nutrients whose consumption should be reduced, regardless of dietary source, food matrix, and composition.

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Dietary fat intake in healthy adolescents: inverse relationships between the estimated intake of saturated fatty acids and serum cholesterol

British Journal Of Nutrition ◽

10.1079/bjn2000279 ◽

2001 ◽

Vol 85 (3) ◽

pp. 333-341 ◽

Cited By ~ 64

Author(s):

Gösta Samuelson ◽

Lars-Erik Bratteby ◽

Rawya Mohsen ◽

Bengt Vessby

Keyword(s):

Fatty Acids ◽

Serum Cholesterol ◽

Milk Fat ◽

Saturated Fatty Acids ◽

Saturated Fat ◽

Dietary Fatty Acids ◽

Cholesterol Esters ◽

Fat Intake ◽

A Chain ◽

The One

The objective of the present study was to describe the intake of dietary fatty acids among healthy 15-year-old boys and girls and to relate the intake of specific fatty acids and the fatty acid composition of the serum cholesterol esters to serum lipid, apolipoprotein (Apo) and insulin concentrations respectively. Fifty-two girls and forty-two boys were randomly selected from the official population register. Unexpectedly, significant inverse associations were found between the dietary content of saturated fatty acids with a chain length of four to fifteen C atoms, mainly derived from milk fat, as well as the corresponding fatty acids in the serum cholesterol esters, on the one hand and the serum concentrations of cholesterol and ApoB on the other. The estimated dietary intake of 4:0–10:0, 12:0 and 14:0 respectively, were all significantly inversely related to the serum cholesterol (r-0.32,r-0.31,r-0.30, all P<0.05) and ApoB (r-0.42,r-0.42, andr-0.40, all P<0.05) concentrations in girls and 12:0 to the ApoB concentration (r-0.55, P<0.01) in boys. The proportions of 12:0 and 15:0 in the serum cholesterol esters were negatively correlated with the serum cholesterol concentrations in both girls (r-0.34,r-0.32, P<0.05) and boys (r-0.53, P<0.01;r-0.32, P<0.05) and with the ApoB concentrations among boys (r-0.61, P<0.01;r-0.43, P<0.05). It is conceivable that milk fat contains or is associated with some component in the diet, or some other characteristics of the food intake, which counterbalances the expected positive relationships between saturated fat intake and lipid levels.

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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

Journal of Nutrition ◽

10.1093/jn/nxz044 ◽

2019 ◽

Vol 149 (6) ◽

pp. 996-1003 ◽

Cited By ~ 2

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.

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Use of Tiger Nut (Cyperus esculentus L.) Oil Emulsion as Animal Fat Replacement in Beef Burgers

Foods ◽

10.3390/foods9010044 ◽

2020 ◽

Vol 9 (1) ◽

pp. 44 ◽

Cited By ~ 20

Author(s):

Julliane Carvalho Barros ◽

Paulo E. S. Munekata ◽

Francisco Allan Leandro de Carvalho ◽

Mirian Pateiro ◽

Francisco J. Barba ◽

...

Keyword(s):

Fatty Acids ◽

Unsaturated Fatty Acids ◽

Saturated Fatty Acids ◽

Meat Product ◽

Saturated Fat ◽

B Value ◽

Cyperus Esculentus ◽

Oil Emulsion ◽

Fat Replacement ◽

Beef Burgers

The present study evaluated the replacement of beef fat in beef burgers using a tiger nut (Cyperus esculentus L.) oil emulsion, in order to reduce total fat and saturated fatty acids in the studied samples. Three formulations were processed: Control—100% beef fat; tiger nut 50% (TN50)—50% of beef fat replaced using tiger nut oil emulsion and tiger nut 100% (TN100)—100% of beef fat replaced by tiger nut oil emulsion. The physicochemical parameters were affected after fat replacement. Moreover, the protein and fat contents decreased in those sample with tiger nut oil emulsion, thus the formulation TN100 can be considered as “reduced fat content”. Regarding color, an increased L* and b* value parameters was observed after TN100 while the values of a* remained similar to the Control samples. The hardness, cohesiveness, gumminess and chewiness were similar in all formulations. The addition of tiger nut oil emulsion as a substitute for beef fat reduced saturated fat and increased the mono- and polyunsaturated fatty acids. Oleic acid was found to be in highest proportions in burgers. The TN100 samples were considered as acceptable by consumers. Therefore, total replacement of beef fat using tiger nut oil emulsions in beef burger resulted in a well-accepted and healthier meat product with reduced total and saturated fat contents, as well as increased unsaturated fatty acids.

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Modern fat technology: what is the potential for heart health?

Proceedings of The Nutrition Society ◽

10.1079/pns2005446 ◽

2005 ◽

Vol 64 (3) ◽

pp. 379-386 ◽

Cited By ~ 40

Author(s):

J. E. Upritchard ◽

M. J. Zeelenberg ◽

H. Huizinga ◽

P. M. Verschuren ◽

E. A. Trautwein

Keyword(s):

Metabolic Syndrome ◽

Fatty Acids ◽

Unsaturated Fatty Acids ◽

Disease Risk ◽

Saturated Fatty Acids ◽

Saturated Fat ◽

Blood Cholesterol ◽

Medical Community ◽

The Metabolic Syndrome ◽

Increased Risk

Saturated andtrans-fatty acids raise total cholesterol and LDL-cholesterol and are known to increase the risk of CHD, while dietary unsaturated fatty acids play important roles in maintaining cardiovascular health. Replacing saturated fats with unsaturated fats in the diet often involves many complex dietary changes. Modifying the composition of foods high in saturated fat, particularly those foods that are consumed daily, can help individuals to meet the nutritional targets for reducing the risk of CHD. In the 1960s the Dutch medical community approached Unilever about the technical feasibility of producing margarine with a high-PUFA and low-saturated fatty acid composition. Margarine is an emulsion of water in liquid oil that is stabilised by a network of fat crystals. In-depth expertise of fat crystallisation processes allowed Unilever scientists to use a minimum of solid fat (saturated fatty acids) to structure a maximum level of PUFA-rich liquid oil, thus developing the first blood-cholesterol-lowering product, Becel. Over the years the composition of this spread has been modified to reflect new scientific findings and recommendations. The present paper will briefly review the developments in fat technology that have made these improvements possible. Unilever produces spreads that are low in total fat and saturated fat, virtually free oftrans-fatty acids and with levels ofn-3 andn-6 PUFA that are in line with the latest dietary recommendations for the prevention of CHD. Individuals with the metabolic syndrome have a 2–4-fold increased risk of developing CHD; therefore, these spreads could make a contribution to CHD prevention in this group. In addition, for individuals with the metabolic syndrome the spreads could be further modified to address their unique dyslipidaemia, i.e. elevated blood triacylglycerols and low HDL-cholesterol. Research conducted in the LIPGENE study and other dietary intervention studies will deliver the scientific evidence to justify further modifications in the composition of spreads that are healthy for the heart disease risk factors associated with the metabolic syndrome.

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Animal fats and human health

Proceedings of the British Society of Animal Science ◽

10.1017/s1752756200013727 ◽

2003 ◽

Vol 2003 ◽

pp. 214-214 ◽

Cited By ~ 1

Author(s):

A.M. Salter

Keyword(s):

Fatty Acids ◽

Total Energy ◽

Plasma Cholesterol ◽

Saturated Fatty Acids ◽

Saturated Fat ◽

Fat Intake ◽

Central Target ◽

Animal Fats ◽

Obesity And Diabetes ◽

Total Fat

In 1991 it was recommended that total fat intake in the UK should be reduced to a population average of less that 33% of total daily energy intake and that saturated fatty acids should contribute no more than 10% of total energy (Department of Health, 1991). A further recommendation was that the intake of trans fatty acids should not exceed 2% of total energy. These recommendations were made primarily on the basis of the influence of fatty acids on plasma cholesterol and thereby on the development of cardiovascular disease. While associations of fat intake with other chronic diseases such as cancer, obesity and diabetes have also been suggested, it was felt that there was insufficient evidence to make specific recommendations on the basis of such claims. A reduction in saturated fat intake has remained a central target of public health nutrition within the United Kingdom ever since. Despite concerted efforts, particularly throughout the 1990s., to achieve these targets little progress has been made. In 2000, total fat intake remained at 38% and saturated fatty acid intake at 15% (DEFRA, 2001).

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Dietary fat modifies thromboxane A2-induced stimulation of rat platelets

Biochemical Journal ◽

10.1042/bj2780399 ◽

1991 ◽

Vol 278 (2) ◽

pp. 399-404 ◽

Cited By ~ 21

Author(s):

J W M Heemskerk ◽

M A H Feijge ◽

A Kester ◽

G Hornstra

Keyword(s):

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Inositol Phosphates ◽

Saturated Fatty Acids ◽

Saturated Fat ◽

Thromboxane A2 ◽

The Other ◽

Thromboxane B2 ◽

Induced Aggregation ◽

Rat Platelets

Diets containing high levels of monounsaturated, n-6 polyunsaturated and n-3 polyunsaturated fatty acids were fed to Wistar rats. This resulted in decreases in the arachidonate content in platelet phospholipids to 91%, 79% and 51% respectively of the level found after feeding a diet rich in saturated fatty acids. In the presence of CaCl2, collagen- and thrombin-induced aggregation of washed platelets from the saturated-fat dietary group (with highest level of arachidonate) was low compared with that of platelets from the other dietary groups, despite a relatively high production of thromboxane B2. On the other hand, n-3 polyunsaturated fatty acids in the diet resulted in platelets aggregating actively, but producing low levels of levels of thromboxane B2. When indomethacin-treated rat platelets were activated with the thromboxane A2 analogue U46619, the presence of a second agonist such as collagen. ADP or thrombin was necessary for aggregate formation. U46619-induced aggregation in combination with either co-activator was relatively low in arachidonate-rich platelets, and was higher in platelets with a low arachidonate content. Similarly, phospholipase C-catalysed formation of L-myo-inositol phosphates was higher in platelets with a low arachidonate content. We conclude that the ability of platelets to react with thromboxane A2 is modified by diet in such a way that a decreased substrate-limited generation of thromboxane A2 is compensated for by an increased response to thromboxane, and vice versa. No significant differences were detected in the binding of U46619 or SQ29548 to platelets from the various dietary groups. Therefore the changed response seems not to be caused by modified properties of the thromboxane A2/prostaglandin H2 receptors, but by altered transduction of the thromboxane signal.

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Energy under-reporting in Swedish and Irish dietary surveys: implications for food-based dietary guidelines

British Journal Of Nutrition ◽

10.1017/s0007114599000975 ◽

1999 ◽

Vol 81 (S1) ◽

pp. S127-S131 ◽

Cited By ~ 33

Author(s):

Wulf Becker ◽

Sharon Foley ◽

Emer Shelley ◽

Michael Gibney

Keyword(s):

Fatty Acids ◽

Energy Intake ◽

Saturated Fatty Acids ◽

Saturated Fat ◽

Dietary Guidelines ◽

Dietary Survey ◽

Eating Occasion ◽

Dietary Surveys ◽

Definition Of ◽

Swedish Data

An analysis of dietary survey data from Sweden and Ireland revealed that with a declining ratio of energy intake to estimated basal metabolic rate (EI : BMR), %energy from fat, saturated fat and carbohydrate fell while that of protein increased. However, where the definition of under-reporting is less strict, as in the Irish database (EI : BMR) < (1·27), the quantitative effect on macronutrient balance, while statistically significant, is not of such magnitude as to be of nutritional significance. However, with respect to foods, under-reporting was found to be of considerable significance in using such data to formulate food-based dietary guidelines. The Swedish data show that under-reporting of foods is associated with a decreasing percentage of consumers, decreasing intake per eating occasion and decreasing frequency of eating. The development of food-based dietary guidelines will involve comparisons of patterns of food intake among people with contrasting high or low intakes of target nutrients. The Swedish data compared food intakes for those with low or high intakes of saturated fatty acids (SFA) among under-reporters and acceptable reporters of energy intake. Whereas absolute values were always lower with the lower EI : BMR group (< 1·1) compared to the higher EI : BMR group (> 1·35) the ratio of intakes for the low vs. high SFA groups were broadly significant at either EI : BMR ratio. This paper highlights the difficulties that under-reporting will pose for food-based dietary guidelines.

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