scholarly journals Estrogen Regulation of Adiposity and Fuel Partitioning

2005 ◽  
Vol 280 (43) ◽  
pp. 35983-35991 ◽  
Author(s):  
Tara M. D'Eon ◽  
Sandra C. Souza ◽  
Mark Aronovitz ◽  
Martin S. Obin ◽  
Susan K. Fried ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Energy Intake ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Regulatory Element ◽  
Estrogen Regulation ◽  
Lipogenic Genes ◽  
Element Binding Protein ◽  
Amp Activated Protein Kinase

Menopause is associated with increased adiposity and greater risk of metabolic disease. In the ovariectomized (OVX) rodent model of menopause, increased adiposity is prevented by estrogen (E2) replacement, reflecting both anorexigenic and potentially metabolic actions of E2. To elucidate metabolic and molecular mechanisms by which E2 regulates fat storage and fat mobilization independently of reduced energy intake, C57 BL/6 mice were ovariectomized, randomized to estrogen (OVX-E2) or control pellet implants (OVX-C), and pairfed for 40 days. E2 treatment was associated with reduced adipose mass and adipocyte size and down-regulation of lipogenic genes in adipocytes under the control of sterol-regulatory element-binding protein 1c. Adipocytes of OVX-E2 mice contained >3-fold more perilipin protein than adipocytes of pairfed control (OVX) mice, and this difference was associated with enhanced ex vivo lipolytic response to catecholamines and with greater levels of serum-free fatty acids following fasting. As in adipose tissue, E2 decreased the expression of lipogenic genes in liver and skeletal muscle. In the latter, E2 appears to promote the partitioning of free fatty acids toward oxidation and away from triglyceride storage by up-regulating the expression of peroxisome proliferation activator receptor-δ and its downstream targets and also by directly and rapidly activating AMP-activated protein kinase. Thus, novel genomic and non-genomic actions of E2 promote leanness in OVX mice independently of reduced energy intake.

scholarly journals Beneficial Effects of SREBP Decoy Oligodeoxynucleotide in an Animal Model of Hyperlipidemia

2020 ◽  
Vol 21 (2) ◽  
pp. 552 ◽  
Author(s):  
Hyun-Jin An ◽  
Jung-Yeon Kim ◽  
Mi-Gyeong Gwon ◽  
Hyemin Gu ◽  
Hyun-Ju Kim ◽  
...  
Keyword(s):  
Animal Model ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Regulatory Element ◽  
Alcoholic Fatty Liver ◽  
Health Crisis ◽  
Beneficial Effects ◽  
Lipogenic Genes ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Hyperlipidemia is a chronic disorder that plays an important role in the development of cardiovascular diseases, type II diabetes, atherosclerosis, hypertension, and non-alcoholic fatty liver disease. Hyperlipidemias have created a worldwide health crisis and impose a substantial burden not only on personal health but also on societies and economies. Transcription factors in the sterol regulatory element binding protein (SREBP) family are key regulators of the lipogenic genes in the liver. SREBPs regulate lipid homeostasis by controlling the expression of a range of enzymes required for the synthesis of endogenous cholesterol, fatty acids, triacylglycerol, and phospholipids. Thereby, SREBPs have been considered as targets for the treatment of metabolic diseases. The aim of this study was to investigate the beneficial functions and the possible underlying molecular mechanisms of SREBP decoy ODN, which is a novel inhibitor of SREBPs, in high-fat diet (HFD)-fed hyperlipidemic mice. Our studies using HFD-induced hyperlipidemia animal model revealed that SREBB decoy ODN inhibited the increased expression of fatty acid synthetic pathway, such as SREBP-1c, FAS, SCD-1, ACC1, and HMGCR. In addition, SREBP decoy ODN decreased pro-inflammatory cytokines, including TNF-α, IL-1β, IL-8, and IL-6 expression. These results suggest that SREBP decoy ODN exerts its anti-hyperlipidemia effects in HFD-induced hyperlipidemia mice by regulating their lipid metabolism and inhibiting lipogenesis through inactivation of the SREPB pathway.

scholarly journals Spatiotemporal dynamics of triglyceride storage in unilocular adipocytes

2014 ◽  
Vol 25 (25) ◽  
pp. 4096-4105 ◽  
Author(s):  
Michael Chu ◽  
Harini Sampath ◽  
David Y. Cahana ◽  
Christoph A. Kahl ◽  
Romel Somwar ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Free Fatty Acids ◽  
Lipid Droplets ◽  
Ex Vivo ◽  
Spatiotemporal Dynamics ◽  
Biological Features ◽  
Adipocyte Hypertrophy ◽  
Cellular Organelles

The spatiotemporal dynamics of triglyceride (TG) storage in unilocular adipocytes are not well understood. Here we applied ex vivo technology to study trafficking and metabolism of fluorescent fatty acids in adipose tissue explants. Live imaging revealed multiple cytoplasmic nodules surrounding the large central lipid droplet (cLD) of unilocular adipocytes. Each cytoplasmic nodule harbors a series of closely associated cellular organelles, including micro–lipid droplets (mLDs), mitochondria, and the endoplasmic reticulum. Exogenously added free fatty acids are rapidly adsorbed by mLDs and concurrently get esterified to TG. This process is greatly accelerated by insulin. mLDs transfer their content to the cLD, serving as intermediates that mediate packaging of newly synthesized TG in the large interior of a unilocular adipocyte. This study reveals novel cell biological features that may contribute to the mechanism of adipocyte hypertrophy.

scholarly journals Association of a polymorphism in SREBP1 with fatty acid composition and lipogenic gene expression in beef cattle breeds

2019 ◽  
Author(s):  
David Gamarra ◽  
Noelia Aldai ◽  
Aisaku Arakawa ◽  
Marian M. de Pancorbo ◽  
Masaaki Taniguchi
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Regulatory Element ◽  
Northern Spain ◽  
Lipogenic Gene ◽  
Lipogenic Genes ◽  
Fa Composition ◽  
Element Binding Protein ◽  
Definition Of ◽  
Lipogenic Gene Transcription

Abstract Background Sterol regulatory element-binding protein 1 (SREBP1) plays an important role in the lipogenesis and fatty acid (FA) composition in fat cells and is consequently considered to influence the nutritional quality of beef. SREBP1 regulates lipogenic gene transcription including stearoyl-CoA desaturases (SCDs) that are responsible for unsaturation of FAs. Therefore, we performed phylogenetic analysis on SREBP1 gene sequences, including 84 bp-indel, among mammals to elucidate the evolutionary importance of this polymorphism and possible effect in the FA composition. Additionally, we analyzed the association between the indel, FA composition, and gene expression of SREBP1 and SCDs in backfat of several commercial type beef breeds in northern Spain (Pirenaica, Salers and Holstein-Friesian).Results In ruminants, the indel region was relatively highly conserved in comparison with the rest of intron 5 sequence or mRNA of SREBP1, suggesting the potential functionality throughout evolution. We applied the definition of the insertion and deletion of 84 bp in intron 5: S (Short) and L (Long) alleles, respectively. Then, we figured the indel is associated with saturated FA (SFA) and several polyunsaturated FA (PUFA) depending on commercial type, specifically Pirenaica bulls, whose SS/SL genotype has been associated with a higher content of 18:0, n-3 and 18:3n-3 (p < 0.05). In Salers, S allele showed the highest frequency (0.385) among all breeds, while SS genotype had high positive correlations between SREBP1 gene expression and UFA contents. Significant correlations between SCD1 and SFAs (16:0) in SL genotype of Pirenaica bulls, but also 9c-16:1 in Pirenaica breed (p < 0.05), suggests a differential relationship between SCD1 and 16:0/9c-16:1 FA contents depending on the indel genotype in this breed. Overall, SS and SS/SL genotypes had a positive correlation between SCD5 and 18:0 (p < 0.05) and a negative correlation between SCD5 and 9c-18:1 (p > 0.05).Conclusions These results suggest that the indel is associated with SFA and PUFA content depending on commercial type. Moreover, the correlations between lipogenic genes (SREBP1 and SCDs) with 16:0 and 9c-16:1, but also 18:0 and 9c-18:1, seems to be attributed to the indel genotype. These findings are useful for beef/dairy breeding to supply nutritionally favorable products.

scholarly journals Effect of Free Fatty Acids on Inflammatory Gene Expression and Hydrogen Peroxide Production by Ex Vivo Blood Mononuclear Cells

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 146 ◽  
Author(s):  
Antoni Sureda ◽  
Miquel Martorell ◽  
Maria del Mar Bibiloni ◽  
Cristina Bouzas ◽  
Laura Gallardo-Alfaro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
H2o2 Production ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Blood Mononuclear Cells ◽  
Docosahexaenoic Acids

The aim of this study was to assess free fatty acids’ (FAs) ex vivo anti-/proinflammatory capabilities and their influence on inflammatory gene expression and H2O2 production by human peripheral blood mononuclear cells (PBMCs). Anthropometric and clinical measurements were performed in 26 participants with metabolic syndrome. Isolated PBMCs were incubated ex vivo for 2 h with several free fatty acids—palmitic, oleic, α-linolenic, γ-linolenic, arachidonic and docosahexaenoic at 50 μM, and lipopolysaccharide (LPS) alone or in combination. H2O2 production and IL6, NFκB, TLR2, TNFα, and COX-2 gene expressions were determined. Palmitic, γ-linolenic, and arachidonic acids showed minor effects on inflammatory gene expression, whereas oleic, α-linolenic, and docosahexaenoic acids reduced proinflammatory gene expression in LPS-stimulated PBMCs. Arachidonic and α-linolenic acids treatment enhanced LPS-stimulated H2O2 production by PBMCs, while palmitic, oleic, γ-linolenic, and docosahexaenoic acids did not exert significant effects. Oleic, α-linolenic, and docosahexaenoic acids induced anti-inflammatory responses in PBMCs. Arachidonic and α-linolenic acids enhanced the oxidative status of LPS-stimulated PBMCs. In conclusion, PBMC ex vivo assays are useful to assess the anti-/proinflammatory and redox-modulatory effects of fatty acids or other food bioactive compounds.

scholarly journals Effect of High-Fat Diets on Oxidative Stress, Cellular Inflammatory Response and Cognitive Function

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2579 ◽  
Author(s):  
Bee Ling Tan ◽  
Mohd Esa Norhaizan
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Cognitive Dysfunction ◽  
Molecular Mechanisms ◽  
Cell Mediated Immunity ◽  
Low Grade ◽  
High Fat ◽  
Cellular Inflammatory Response

Cognitive dysfunction is linked to chronic low-grade inflammatory stress that contributes to cell-mediated immunity in creating an oxidative environment. Food is a vitally important energy source; it affects brain function and provides direct energy. Several studies have indicated that high-fat consumption causes overproduction of circulating free fatty acids and systemic inflammation. Immune cells, free fatty acids, and circulating cytokines reach the hypothalamus and initiate local inflammation through processes such as microglial proliferation. Therefore, the role of high-fat diet (HFD) in promoting oxidative stress and neurodegeneration is worthy of further discussion. Of particular interest in this article, we highlight the associations and molecular mechanisms of HFD in the modulation of inflammation and cognitive deficits. Taken together, a better understanding of the role of oxidative stress in cognitive impairment following HFD consumption would provide a useful approach for the prevention of cognitive dysfunction.

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 Effects of fatty acids on gene expression: role of peroxisome proliferator-activated receptor α, liver X receptor α and sterol regulatory element-binding protein-1c

2002 ◽  
Vol 61 (3) ◽  
pp. 371-374 ◽  
Author(s):  
Sander Kersten
Keyword(s):  
Fatty Acids ◽  
Binding Protein ◽  
Regulatory Element ◽  
Liver X Receptor ◽  
Dietary Fatty Acids ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Liver X Receptor Α ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Dietary fatty acids have numerous effects on cellular function, many of which are achieved by altering the expression of genes. The present paper reviews recent data on the mechanisms by which fatty acids influence DNA transcription, and focus specifically on the importance of three transcription factors: peroxisome proliferator-activated receptor α; liver X receptor α; sterol regulatory element-binding protein 1c. These data indicate that fatty acids induce or inhibit the mRNA expression of a variety of different genes by acting both as agonists and as antagonists for nuclear hormone receptors.

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.

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