scholarly journals Upregulation of lipid metabolism genes in the breast prior to cancer diagnosis

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Natascia Marino ◽  
Rana German ◽  
Xi Rao ◽  
Ed Simpson ◽  
Sheng Liu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Normal Tissue ◽  
Fatty Acid Transport ◽  
Acid Uptake ◽  
Healthy Controls ◽  
Breast Epithelium ◽  
Cancer Initiation ◽  
Tissue Compartments

Abstract Histologically normal tissue adjacent to the tumor can provide insight of the microenvironmental alterations surrounding the cancerous lesion and affecting the progression of the disease. However, little is known about the molecular changes governing cancer initiation in cancer-free breast tissue. Here, we employed laser microdissection and whole-transcriptome profiling of the breast epithelium prior to and post tumor diagnosis to identify the earliest alterations in breast carcinogenesis. Furthermore, a comprehensive analysis of the three tissue compartments (microdissected epithelium, stroma, and adipose tissue) was performed on the breast donated by either healthy subjects or women prior to the clinical manifestation of cancer (labeled “susceptible normal tissue”). Although both susceptible and healthy breast tissues appeared histologically normal, the susceptible breast epithelium displayed a significant upregulation of genes involved in fatty acid uptake/transport (CD36 and AQP7), lipolysis (LIPE), and lipid peroxidation (AKR1C1). Upregulation of lipid metabolism- and fatty acid transport-related genes was observed also in the microdissected susceptible stromal and adipose tissue compartments, respectively, when compared with the matched healthy controls. Moreover, inter-compartmental co-expression analysis showed increased epithelium-adipose tissue crosstalk in the susceptible breasts as compared with healthy controls. Interestingly, reductions in natural killer (NK)-related gene signature and CD45+/CD20+ cell staining were also observed in the stromal compartment of susceptible breasts. Our study yields new insights into the cancer initiation process in the breast. The data suggest that in the early phase of cancer development, metabolic activation of the breast, together with increased epithelium-adipose tissue crosstalk may create a favorable environment for final cell transformation, proliferation, and survival.

scholarly journals The effect of high glucose on lipid metabolism in the human placenta

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Charlotte H. Hulme ◽  
Anna Nicolaou ◽  
Sharon A. Murphy ◽  
Alexander E. P. Heazell ◽  
Jenny E. Myers ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
High Glucose ◽  
Fatty Acid Uptake ◽  
Fatty Acid Transport ◽  
Acid Uptake ◽  
Obese Women ◽  
Lipid Transfer ◽  
Glucose Levels ◽  
Fatty Acid Transport Proteins

Abstract Diabetes mellitus (DM) during pregnancy can result in fetal overgrowth, likely due to placental dysfunction, which has health consequences for the infant. Here we test our prediction from previous work using a placental cell line that high glucose concentrations affect placental lipid metabolism. Placentas from women with type 1 (n = 13), type 2 (n = 6) or gestational (n = 12) DM, BMI-matched to mothers without DM (n = 18), were analysed for lipase and fatty acid transport proteins and fatty acid and triglyceride content. Explants from uncomplicated pregnancies (n = 6) cultured in physiological or high glucose were similarly analysed. High glucose levels did not alter placental lipase or transporter expression or the profile and abundance of fatty acids, but triglyceride levels were higher (p < 0.05), suggesting reduced β- oxidation. DM did not affect placental protein expression or fatty acid profile. Triglyceride levels of placentas from mothers with pre-existing DM were similar to controls, but higher in obese women with gestational DM. Maternal hyperglycemia may not affect placental fatty acid uptake and transport. However, placental β-oxidation is affected by high glucose and reduced in a subset of women with DM. Abnormal placental lipid metabolism could contribute to increased maternal-fetal lipid transfer and excess fetal growth in some DM pregnancies.

scholarly journals Apolipoprotein A-IV Enhances Fatty Acid Uptake by Adipose Tissues of Male Mice via Sympathetic Activation

Endocrinology ◽  
2020 ◽  
Vol 161 (4) ◽  
Author(s):  
Qi Zhu ◽  
Jonathan Weng ◽  
Minqian Shen ◽  
Jace Fish ◽  
Zhujun Shen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Sympathetic Activity ◽  
Sympathetic Innervation ◽  
Acid Uptake ◽  
Adipose Tissues ◽  
Lipid Mixture ◽  
Apolipoprotein A ◽  
Brown Adipose

Abstract Apolipoprotein A-IV (ApoA-IV) synthesized by the gut regulates lipid metabolism. Sympathetic innervation of adipose tissues also controls lipid metabolism. We hypothesized that ApoA-IV required sympathetic innervation to increase fatty acid (FA) uptake by adipose tissues and brown adipose tissue (BAT) thermogenesis. After 3 weeks feeding of either a standard chow diet or a high-fat diet (HFD), mice with unilateral denervation of adipose tissues received intraperitoneal administration of recombinant ApoA-IV protein and intravenous infusion of lipid mixture with radioactive triolein. In chow-fed mice, ApoA-IV administration increased FA uptake by intact BAT but not the contralateral denervated BAT or intact white adipose tissue (WAT). Immunoblots showed that, in chow-fed mice, ApoA-IV increased expression of lipoprotein lipase and tyrosine hydroxylase in both intact BAT and inguinal WAT (IWAT), while ApoA-IV enhanced protein levels of β3 adrenergic receptor, adipose triglyceride lipase, and uncoupling protein 1 in the intact BAT only. In HFD-fed mice, ApoA-IV elevated FA uptake by intact epididymal WAT (EWAT) but not intact BAT or IWAT. ApoA-IV increased sympathetic activity assessed by norepinephrine turnover (NETO) rate in BAT and EWAT of chow-fed mice, whereas it elevated NETO only in EWAT of HFD-fed mice. These observations suggest that, in chow-fed mice, ApoA-IV activates sympathetic activity of BAT and increases FA uptake by BAT via innervation, while in HFD-fed mice, ApoA-IV stimulates sympathetic activity of EWAT to shunt FAs into the EWAT.

scholarly journals Lipid metabolism in women

2004 ◽  
Vol 63 (1) ◽  
pp. 153-160 ◽  
Author(s):  
Christine M. Williams
Keyword(s):  
Adipose Tissue ◽  
Cardiovascular Risk ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Body Fat ◽  
Adrenergic Receptors ◽  
Subcutaneous Fat ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Fat Depots

Differences in whole-body lipid metabolism between men and women are indicated by lower-body fat accumulation in women but more marked accumulation of fat in the intra-abdominal visceral fat depots of men. Circulating blood lipid concentrations also show gender-related differences. These differences are most marked in premenopausal women, in whom total cholesterol, LDL-cholesterol and triacylglycerol concentrations are lower and HDL-cholesterol concentration is higher than in men. Tendency to accumulate body fat in intra-abdominal fat stores is linked to increased risk of CVD, metabolic syndrome, diabetes and other insulin-resistant states. Differential regional regulation of adipose tissue lipolysis and lipogenesis must underlie gender-related differences in the tendency to accumulate fat in specific fat depots. However, empirical data to support current hypotheses remain limited at the present time because of the demanding and specialist nature of the methods used to study adipose tissue metabolism in human subjects. In vitro and in vivo data show greater lipolytic sensitivity of abdominal subcutaneous fat and lesser lipolytic sensitivity of femoral and gluteal subcutaneous fat in women than in men. These differences appear to be due to fewer inhibitory α adrenergic receptors in abdominal regions and greater α adrenergic receptors in gluteal and femoral regions in women than in men. There do not appear to be major gender-related differences in rates of fatty acid uptake (lipogenesis) in different subcutaneous adipose tissue regions. In visceral fat rates of both lipolysis and lipogenesis appear to be greater in men than in women; higher rates of lipolysis may be due to fewer α adrenergic receptors in this fat depot in men. Fatty acid uptake into this depot in the postprandial period is approximately 7-fold higher in men than in women. Triacylglycerol concentrations appear to be a stronger cardiovascular risk factor in women than in men, with particular implications for cardiovascular risk in diabetic women. The increased triacylglycerol concentrations observed in women taking hormone-replacement therapy (HRT) may explain the paradoxical findings of increased rates of CVD in women taking HRT that have been reported from recent primary and secondary prevention trials of HRT.

scholarly journals Dim Light at Night Disturbs Molecular Pathways of Lipid Metabolism

2020 ◽  
Vol 21 (18) ◽  
pp. 6919
Author(s):  
Monika Okuliarova ◽  
Valentina Sophia Rumanova ◽  
Katarina Stebelova ◽  
Michal Zeman
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Metabolic Diseases ◽  
De Novo ◽  
Negative Impact ◽  
Acid Uptake ◽  
Control Mechanisms ◽  
Light At Night ◽  
Dim Light

Dim light at night (dLAN) is associated with metabolic risk but the specific effects on lipid metabolism have only been evaluated to a limited extent. Therefore, to explore whether dLAN can compromise lipid metabolic homeostasis in healthy individuals, we exposed Wistar rats to dLAN (~2 lx) for 2 and 5 weeks and analyzed the main lipogenic pathways in the liver and epididymal fat pad, including the control mechanisms at the hormonal and molecular level. We found that dLAN promoted hepatic triacylglycerol accumulation, upregulated hepatic genes involved in de novo synthesis of fatty acids, and elevated glucose and fatty acid uptake. These observations were paralleled with suppressed fatty acid synthesis in the adipose tissue and altered plasma adipokine levels, indicating disturbed adipocyte metabolic function with a potential negative impact on liver metabolism. Moreover, dLAN-exposed rats displayed an elevated expression of two peroxisome proliferator-activated receptor family members (Pparα and Pparγ) in the liver and adipose tissue, suggesting the deregulation of important metabolic transcription factors. Together, our results demonstrate that an impaired balance of lipid biosynthetic pathways caused by dLAN can increase lipid storage in the liver, thereby accounting for a potential linking mechanism between dLAN and metabolic diseases.

Changes in fatty acid transport and transporters are related to the severity of insulin deficiency

2002 ◽  
Vol 283 (3) ◽  
pp. E612-E621 ◽  
Author(s):  
Joost J. F. P. Luiken ◽  
Yoga Arumugam ◽  
Rhonda C. Bell ◽  
Jorge Calles-Escandon ◽  
Narendra N. Tandon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Plasma Membrane ◽  
Fatty Acid ◽  
Fatty Acid Transport ◽  
Acid Uptake ◽  
Acid Transport ◽  
Fatty Acid Binding ◽  
Fatty Acid Transporter ◽  
Acid Transporter

We have examined the effects of streptozotocin (STZ)-induced diabetes (moderate and severe) on fatty acid transport and fatty acid transporter (FAT/CD36) and plasma membrane-bound fatty acid binding protein (FABPpm) expression, at the mRNA and protein level, as well as their plasmalemmal localization. These studies have shown that, with STZ-induced diabetes, 1) fatty acid transport across the plasma membrane is increased in heart, skeletal muscle, and adipose tissue and is reduced in liver; 2) changes in fatty acid transport are generally not associated with changes in fatty acid transporter mRNAs, except in the heart; 3) increases in fatty acid transport in heart and skeletal muscle occurred with concomitant increases in plasma membrane FAT/CD36, whereas in contrast, the increase and decrease in fatty acid transport in adipose tissue and liver, respectively, were accompanied by concomitant increments and reductions in plasma membrane FABPpm; and finally, 4) the increases in plasma membrane transporters (FAT/CD36 in heart and skeletal muscle; FABPpm in adipose tissue) were attributable to their increased expression, whereas in liver, the reduced plasma membrane FABPpm appeared to be due to its relocation within the cell in the face of slightly increased expression. Taken together, STZ-induced changes in fatty acid uptake demonstrate a complex and tissue-specific pattern, involving different fatty acid transporters in different tissues, in combination with different underlying mechanisms to alter their surface abundance.

scholarly journals Single-cell analysis of insulin-regulated fatty acid uptake in adipocytes

2010 ◽  
Vol 299 (3) ◽  
pp. E486-E496 ◽  
Author(s):  
Oleg Varlamov ◽  
Romel Somwar ◽  
Anda Cornea ◽  
Paul Kievit ◽  
Kevin L. Grove ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Single Cell ◽  
Cell Size ◽  
Insulin Response ◽  
Fatty Acid Uptake ◽  
Fatty Acid Transport ◽  
Acid Uptake ◽  
Adipocyte Size

Increased body fat correlates with the enlargement of average fat cell size and reduced adipose tissue insulin sensitivity. It is currently unclear whether adipocytes, as they accumulate more triglycerides and grow in size, gradually become less insulin sensitive or whether obesity-related factors independently cause both the enlargement of adipocyte size and reduced adipose tissue insulin sensitivity. In the first instance, large and small adipocytes in the same tissue would exhibit differences in insulin sensitivity, whereas, in the second instance, adipocyte size per se would not necessarily correlate with insulin response. To analyze the effect of adipocyte size on insulin sensitivity, we employed a new single-cell imaging assay that resolves fatty acid uptake and insulin response in single adipocytes in subcutaneous adipose tissue explants. Here, we report that subcutaneous adipocytes are heterogeneous in size and intrinsic insulin sensitivity. Whereas smaller adipocytes respond to insulin by increasing lipid uptake, adipocytes with cell diameters larger than 80–100 μm are insulin resistant. We propose that, when cell size approaches a critical boundary, adipocytes lose insulin-dependent fatty acid transport. This negative feedback mechanism may protect adipocytes from lipid overload and restrict further expansion of adipose tissue, which leads to obesity and metabolic complications.

scholarly journals Identification of the molecular regulation of differences in lipid deposition in dedifferentiated preadipocytes from different chicken tissues

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zheng Ma ◽  
Na Luo ◽  
Lu Liu ◽  
Huanxian Cui ◽  
Jing Li ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Lipid Content ◽  
Regulatory Network ◽  
Total Lipid Content ◽  
Fatty Acid Transport ◽  
Lipid Deposition ◽  
Ppar Signaling ◽  
The Difference

Abstract Background A body distribution with high intramuscular fat and low abdominal fat is the ideal goal for broiler breeding. Preadipocytes with different origins have differences in terms of metabolism and gene expression. The transcriptome analysis performed in this study of intramuscular preadipocytes (DIMFPs) and adipose tissue-derived preadipocytes (DAFPs) aimed to explore the characteristics of lipid deposition in different chicken preadipocytes by dedifferentiation in vitro. Results Compared with DAFPs, the total lipid content in DIMFPs was reduced (P < 0.05). Moreover, 72 DEGs related to lipid metabolism were screened, which were involved in adipocyte differentiation, fatty acid transport and fatty acid synthesis, lipid stabilization, and lipolysis. Among the 72 DEGs, 19 DEGs were enriched in the PPAR signaling pathway, indicating its main contribution to the regulation of the difference in lipid deposition between DAFPs and DIMFPs. Among these 19 genes, the representative APOA1, ADIPOQ, FABP3, FABP4, FABP7, HMGCS2, LPL and RXRG genes were downregulated, but the ACSL1, FABP5, PCK2, PDPK1, PPARG, SCD, SCD5, and SLC27A6 genes were upregulated (P < 0.05 or P < 0.01) in the DIMFPs. In addition, the well-known pathways affecting lipid metabolism (MAPK, TGF-beta and calcium) and the pathways related to cell communication were enriched, which may also contribute to the regulation of lipid deposition. Finally, the regulatory network for the difference in lipid deposition between chicken DAFPs and DIMFPs was proposed based on the above information. Conclusions Our data suggested a difference in lipid deposition between DIMFPs and DAFPs of chickens in vitro and proposed a molecular regulatory network for the difference in lipid deposition between chicken DAFPs and DIMFPs. The lipid content was significantly increased in DAFPs by the direct mediation of PPAR signaling pathways. These findings provide new insights into the regulation of tissue-specific fat deposition and the optimization of body fat distribution in broilers.

Effects of cold acclimation on lipid metabolism in adipose tissue

1961 ◽  
Vol 200 (4) ◽  
pp. 847-850 ◽  
Author(s):  
Judith K. Patkin ◽  
E. J. Masoro
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Cold Acclimation ◽  
Long Chain Fatty Acids ◽  
Synthetic Capacity ◽  
And Control ◽  
Long Chain ◽  
Chain Fatty Acids

Cold acclimation is known to alter hepatic lipid metabolism. Liver slices from cold-acclimated rats have a greatly depressed capacity to synthesize long-chain fatty acids from acctate-1-C14. Since adipose tissue is the major site of lipogenic activity in the intact animal, its fatty acid synthetic capacity was studied. In contrast to the liver, it was found that adipose tissue from the cold-acclimated rat synthesized three to six times as much long-chain fatty acids per milligram of tissue protein as the adipose tissue from the control rat living at 25°C. Evidence is presented indicating that adipose tissue from cold-acclimated and control rats esterify long-chain fatty acids at the same rate. The ability of adipose tissue to oxidize palmitic acid to CO2 was found to be unaltered by cold acclimation. The fate of the large amount of fatty acid synthesized in the adipose tissue of cold-acclimated rats is discussed.

scholarly journals Lipid Accumulation and Chronic Kidney Disease

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 722 ◽  
Author(s):  
Zhibo Gai ◽  
Tianqi Wang ◽  
Michele Visentin ◽  
Gerd Kullak-Ublick ◽  
Xianjun Fu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Kidney Disease ◽  
Lipid Accumulation ◽  
Scavenger Receptor ◽  
Fatty Acid Uptake ◽  
Lipid Lowering ◽  
Fatty Acid Transport ◽  
Acid Uptake

Obesity and hyperlipidemia are the most prevalent independent risk factors of chronic kidney disease (CKD), suggesting that lipid accumulation in the renal parenchyma is detrimental to renal function. Non-esterified fatty acids (also known as free fatty acids, FFA) are especially harmful to the kidneys. A concerted, increased FFA uptake due to high fat diets, overexpression of fatty acid uptake systems such as the CD36 scavenger receptor and the fatty acid transport proteins, and a reduced β-oxidation rate underlie the intracellular lipid accumulation in non-adipose tissues. FFAs in excess can damage podocytes, proximal tubular epithelial cells and the tubulointerstitial tissue through various mechanisms, in particular by boosting the production of reactive oxygen species (ROS) and lipid peroxidation, promoting mitochondrial damage and tissue inflammation, which result in glomerular and tubular lesions. Not all lipids are bad for the kidneys: polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) seem to help lag the progression of chronic kidney disease (CKD). Lifestyle interventions, especially dietary adjustments, and lipid-lowering drugs can contribute to improve the clinical outcome of patients with CKD.

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