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.

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 Inhibition of Ghrelin Activity by Receptor Antagonist [d-Lys-3] GHRP-6 Attenuates Alcohol-Induced Hepatic Steatosis by Regulating Hepatic Lipid Metabolism

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 517 ◽  
Author(s):  
Karuna Rasineni ◽  
Jacy L. Kubik ◽  
Carol A. Casey ◽  
Kusum K. Kharbanda
Keyword(s):  
Insulin Secretion ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Receptor Antagonist ◽  
Hepatic Steatosis ◽  
De Novo ◽  
Serum Insulin ◽  
Acid Uptake ◽  
Hepatic Lipid ◽  
Insulin Levels

Alcoholic steatosis, characterized by an accumulation of triglycerides in hepatocytes, is one of the earliest pathological changes in the progression of alcoholic liver disease. In our previous study, we showed that alcohol-induced increase in serum ghrelin levels impair insulin secretion from pancreatic β-cells. The consequent reduction in the circulating insulin levels promote adipose-derived fatty acid mobilization to ultimately contribute to hepatic steatosis. In this study, we determined whether inhibition of ghrelin activity in chronic alcohol-fed rats could improve hepatic lipid homeostasis at the pancreas–adipose–liver axis. Adult Wistar rats were fed Lieber-DeCarli control or an ethanol liquid diet for 7 weeks. At 6 weeks, a subset of rats in each group were injected with either saline or ghrelin receptor antagonist, [d-Lys-3] GHRP-6 (DLys; 9 mg/kg body weight) for 5 days and all rats were sacrificed 2 days later. DLys treatment of ethanol rats improved pancreatic insulin secretion, normalized serum insulin levels, and the adipose lipid metabolism, as evidenced by the decreased serum free fatty acids (FFA). DLys treatment of ethanol rats also significantly decreased the circulating FFA uptake, de novo hepatic fatty acid synthesis ultimately attenuating alcoholic steatosis. To summarize, inhibition of ghrelin activity reduced alcoholic steatosis by improving insulin secretion, normalizing serum insulin levels, inhibiting adipose lipolysis, and preventing fatty acid uptake and synthesis in the liver. Our studies provided new insights on the important role of ghrelin in modulating the pancreas–adipose–liver, and promoting adipocyte lipolysis and hepatic steatosis. The findings offer a therapeutic approach of not only preventing alcoholic liver injury but also treating it.

Differences in transport of fatty acids and expression of fatty acid transporting proteins in adipose tissue of obese black and white women

2006 ◽  
Vol 290 (1) ◽  
pp. E87-E91 ◽  
Author(s):  
Joseph F. Bower ◽  
Julianne M. Davis ◽  
Enhui Hao ◽  
Hisham A. Barakat
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
African American Women ◽  
White Women ◽  
De Novo ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Omental Adipose Tissue ◽  
Protein Levels

We have reported that the rate of de novo triglyceride (TG) synthesis by omental, but not subcutaneous, adipose tissue was higher in African-American women (AAW) than in Caucasian women (CAW). The purpose of this study was to explore the potential mechanisms underlying this increase. Toward that end, we determined the activities of key enzymes in the pathway of TG synthesis, the rates of uptake of fatty acids by adipocytes, mRNA and protein levels of the fatty acid-transporting proteins FAT/CD36 and FATP, and mRNA and protein levels of PPARγ in omental fat of AAW and CAW. The results showed 1) no difference in the activity of phosphofructokinase, glycerol-3-phosphate dehydrogenase, or diacylglycerol acyltransferase; 2) a higher rate of fatty acid uptake by adipocytes of the AAW; 3) an increase in the mRNA and protein levels of CD36 and FATP4 in the fat of the AAW; and 4) an increase in the mRNA and protein levels of PPARγ, which can stimulate the expression of CD36 and FATP. These results suggest that the increase in the transport of fatty acid, which is mediated by the overexpression of the transport proteins in the omental adipose tissue of the AAW, might contribute to the higher prevalence of obesity in AAW.

Conjugated Linoleic Acid (t-10, c-12) Reduces Fatty Acid Synthesis de Novo, but not Expression of Genes for Lipid Metabolism in Bovine Adipose Tissue ex Vivo

Lipids ◽  
2013 ◽  
Vol 49 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Seong Ho Choi ◽  
David T. Silvey ◽  
Bradley J. Johnson ◽  
Matthew E. Doumit ◽  
Ki Yong Chung ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Linoleic Acid ◽  
Conjugated Linoleic Acid ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Ex Vivo ◽  
Acid Synthesis ◽  
Expression Of Genes

Suppressing fatty acid uptake has therapeutic effects in preclinical models of prostate cancer

2019 ◽  
Vol 11 (478) ◽  
pp. eaau5758 ◽  
Author(s):  
Matthew J. Watt ◽  
Ashlee K. Clark ◽  
Luke A. Selth ◽  
Vanessa R. Haynes ◽  
Natalie Lister ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
De Novo ◽  
Human Cancer ◽  
Critical Role ◽  
Fatty Acid Uptake ◽  
De Novo Lipogenesis ◽  
Therapeutic Effects ◽  
Acid Uptake

Metabolism alterations are hallmarks of cancer, but the involvement of lipid metabolism in disease progression is unclear. We investigated the role of lipid metabolism in prostate cancer using tissue from patients with prostate cancer and patient-derived xenograft mouse models. We showed that fatty acid uptake was increased in human prostate cancer and that these fatty acids were directed toward biomass production. These changes were mediated, at least partly, by the fatty acid transporter CD36, which was associated with aggressive disease. Deleting Cd36 in the prostate of cancer-susceptible Pten−/− mice reduced fatty acid uptake and the abundance of oncogenic signaling lipids and slowed cancer progression. Moreover, CD36 antibody therapy reduced cancer severity in patient-derived xenografts. We further demonstrated cross-talk between fatty acid uptake and de novo lipogenesis and found that dual targeting of these pathways more potently inhibited proliferation of human cancer-derived organoids compared to the single treatments. These findings identify a critical role for CD36-mediated fatty acid uptake in prostate cancer and suggest that targeting fatty acid uptake might be an effective strategy for treating prostate cancer.

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 Annexins in Adipose Tissue: Novel Players in Obesity

2019 ◽  
Vol 20 (14) ◽  
pp. 3449 ◽  
Author(s):  
Thomas Grewal ◽  
Carlos Enrich ◽  
Carles Rentero ◽  
Christa Buechler
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Glucose Transporter ◽  
Metabolic Diseases ◽  
Cell Metabolism ◽  
Fatty Acid Uptake ◽  
Membrane Microdomains ◽  
Acid Uptake ◽  
Dependent Manner ◽  
Membrane Microdomain

Obesity and the associated comorbidities are a growing health threat worldwide. Adipose tissue dysfunction, impaired adipokine activity, and inflammation are central to metabolic diseases related to obesity. In particular, the excess storage of lipids in adipose tissues disturbs cellular homeostasis. Amongst others, organelle function and cell signaling, often related to the altered composition of specialized membrane microdomains (lipid rafts), are affected. Within this context, the conserved family of annexins are well known to associate with membranes in a calcium (Ca2+)- and phospholipid-dependent manner in order to regulate membrane-related events, such as trafficking in endo- and exocytosis and membrane microdomain organization. These multiple activities of annexins are facilitated through their diverse interactions with a plethora of lipids and proteins, often in different cellular locations and with consequences for the activity of receptors, transporters, metabolic enzymes, and signaling complexes. While increasing evidence points at the function of annexins in lipid homeostasis and cell metabolism in various cells and organs, their role in adipose tissue, obesity and related metabolic diseases is still not well understood. Annexin A1 (AnxA1) is a potent pro-resolving mediator affecting the regulation of body weight and metabolic health. Relevant for glucose metabolism and fatty acid uptake in adipose tissue, several studies suggest AnxA2 to contribute to coordinate glucose transporter type 4 (GLUT4) translocation and to associate with the fatty acid transporter CD36. On the other hand, AnxA6 has been linked to the control of adipocyte lipolysis and adiponectin release. In addition, several other annexins are expressed in fat tissues, yet their roles in adipocytes are less well examined. The current review article summarizes studies on the expression of annexins in adipocytes and in obesity. Research efforts investigating the potential role of annexins in fat tissue relevant to health and metabolic disease are discussed.

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.

Sign in / Sign up

Export Citation Format

Share Document