scholarly journals Lipid Identification and Transcriptional Analysis of Controlling Enzymes in Bovine Ovarian Follicle

2018 ◽  
Vol 19 (10) ◽  
pp. 3261 ◽  
Author(s):  
Priscila Bertevello ◽  
Ana-Paula Teixeira-Gomes ◽  
Alexandre Seyer ◽  
Anaïs Vitorino Carvalho ◽  
Valérie Labas ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Composition ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Ovarian Follicle ◽  
Ovarian Follicles ◽  
De Novo Lipogenesis ◽  
Transcriptional Analysis ◽  
Follicular Cells ◽  
Metabolism Regulation

Ovarian follicle provides a favorable environment for enclosed oocytes, which acquire their competence in supporting embryo development in tight communications with somatic follicular cells and follicular fluid (FF). Although steroidogenesis in theca (TH) and granulosa cells (GC) is largely studied, and the molecular mechanisms of fatty acid (FA) metabolism in cumulus cells (CC) and oocytes are emerging, little data is available regarding lipid metabolism regulation within ovarian follicles. In this study, we investigated lipid composition and the transcriptional regulation of FA metabolism in 3–8 mm ovarian follicles in bovine. Using liquid chromatography and mass spectrometry (MS), 438 and 439 lipids were identified in FF and follicular cells, respectively. From the MALDI-TOF MS lipid fingerprints of FF, TH, GC, CC, and oocytes, and the MS imaging of ovarian sections, we identified 197 peaks and determined more abundant lipids in each compartment. Transcriptomics revealed lipid metabolism-related genes, which were expressed constitutively or more specifically in TH, GC, CC, or oocytes. Coupled with differential lipid composition, these data suggest that the ovarian follicle contains the metabolic machinery that is potentially capable of metabolizing FA from nutrient uptake, degrading and producing lipoproteins, performing de novo lipogenesis, and accumulating lipid reserves, thus assuring oocyte energy supply, membrane synthesis, and lipid-mediated signaling to maintain follicular homeostasis.

scholarly journals Lipid Metabolism Is Dysregulated before, during and after Pregnancy in a Mouse Model of Gestational Diabetes

2021 ◽  
Vol 22 (14) ◽  
pp. 7452
Author(s):  
Samuel Furse ◽  
Denise S. Fernandez-Twinn ◽  
Davide Chiarugi ◽  
Albert Koulman ◽  
Susan E. Ozanne
Keyword(s):  
Lipid Metabolism ◽  
Gestational Diabetes ◽  
Glucose Tolerance ◽  
Mouse Model ◽  
Time Course ◽  
De Novo ◽  
Lipid Analysis ◽  
Temporal Distribution ◽  
De Novo Lipogenesis ◽  
Analysis Tool

The aim of the current study was to test the hypothesis that maternal lipid metabolism was modulated during normal pregnancy and that these modulations are altered in gestational diabetes mellitus (GDM). We tested this hypothesis using an established mouse model of diet-induced obesity with pregnancy-associated loss of glucose tolerance and a novel lipid analysis tool, Lipid Traffic Analysis, that uses the temporal distribution of lipids to identify differences in the control of lipid metabolism through a time course. Our results suggest that the start of pregnancy is associated with several changes in lipid metabolism, including fewer variables associated with de novo lipogenesis and fewer PUFA-containing lipids in the circulation. Several of the changes in lipid metabolism in healthy pregnancies were less apparent or occurred later in dams who developed GDM. Some changes in maternal lipid metabolism in the obese-GDM group were so late as to only occur as the control dams’ systems began to switch back towards the non-pregnant state. These results demonstrate that lipid metabolism is modulated in healthy pregnancy and the timing of these changes is altered in GDM pregnancies. These findings raise important questions about how lipid metabolism contributes to changes in metabolism during healthy pregnancies. Furthermore, as alterations in the lipidome are present before the loss of glucose tolerance, they could contribute to the development of GDM mechanistically.

scholarly journals Signalling pathways and mechanistic cues highlighted by transcriptomic analysis of primordial, primary, and secondary ovarian follicles in domestic cat

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shauna Kehoe ◽  
Katarina Jewgenow ◽  
Paul R. Johnston ◽  
Susan Mbedi ◽  
Beate C. Braun
Keyword(s):  
Gene Expression ◽  
Transforming Growth Factor ◽  
Ovarian Follicle ◽  
Mammalian Species ◽  
Expression Patterns ◽  
Ovarian Follicles ◽  
Domestic Cat ◽  
Transcriptional Analysis ◽  
Ovarian Folliculogenesis

AbstractIn vitro growth (IVG) of dormant primordial ovarian follicles aims to produce mature competent oocytes for assisted reproduction. Success is dependent on optimal in vitro conditions complemented with an understanding of oocyte and ovarian follicle development in vivo. Complete IVG has not been achieved in any other mammalian species besides mice. Furthermore, ovarian folliculogenesis remains sparsely understood overall. Here, gene expression patterns were characterised by RNA-sequencing in primordial (PrF), primary (PF), and secondary (SF) ovarian follicles from Felis catus (domestic cat) ovaries. Two major transitions were investigated: PrF-PF and PF-SF. Transcriptional analysis revealed a higher proportion in gene expression changes during the PrF-PF transition. Key influencing factors during this transition included the interaction between the extracellular matrix (ECM) and matrix metalloproteinase (MMPs) along with nuclear components such as, histone HIST1H1T (H1.6). Conserved signalling factors and expression patterns previously described during mammalian ovarian folliculogenesis were observed. Species-specific features during domestic cat ovarian folliculogenesis were also found. The signalling pathway terms “PI3K-Akt”, “transforming growth factor-β receptor”, “ErbB”, and “HIF-1” from the functional annotation analysis were studied. Some results highlighted mechanistic cues potentially involved in PrF development in the domestic cat. Overall, this study provides an insight into regulatory factors and pathways during preantral ovarian folliculogenesis in domestic cat.

scholarly journals Glial Hedgehog and lipid metabolism regulate neural stem cell proliferation in Drosophila

2020 ◽  
Author(s):  
Qian Dong ◽  
Michael Zavortink ◽  
Francesca Froldi ◽  
Sofya Golenkina ◽  
Tammy Lam ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Cell Cycle Progression ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Post Translational Modification ◽  
Final Size ◽  
Neural Lineage ◽  
Signalling Molecule ◽  
Lipid Metabolism Genes ◽  
And Function

AbstractThe final size and function of the adult central nervous system (CNS) is determined by neuronal lineages generated by neural stem cells (NSCs) in the developing brain. In Drosophila, NSCs called neuroblasts (NBs) reside within a specialised microenvironment called the glial niche. Here, we explore non-autonomous glial regulation of NB proliferation. We show that lipid droplets (LDs) which reside within the glial niche are closely associated with the signalling molecule Hedgehog (Hh). Under physiological conditions, cortex glial Hh is autonomously required to sustain niche chamber formation, and non-autonomously restrained to prevent ectopic Hh signalling in the NBs. In the context of cortex glial overgrowth, induced by Fibroblast Growth Factor (FGF) activation, Hh and lipid storage regulators Lsd-2 and Fasn1 were upregulated, resulting in activation of Hh signalling in the NBs; which in turn disrupted NB cell cycle progression and reduced neuronal production. We show that the LD regulator Lsd-2 modulates Hh’s ability to signal to NBs, and de novo lipogenesis gene Fasn1 regulates Hh post-translational modification via palmitoylation. Together, our data suggest that the glial niche non-autonomously regulates NB proliferation and neural lineage size via Hh signaling that is modulated by lipid metabolism genes.

scholarly journals AMPK Activation Reduces Hepatic Lipid Content by Increasing Fat Oxidation In Vivo

2018 ◽  
Vol 19 (9) ◽  
pp. 2826 ◽  
Author(s):  
Marc Foretz ◽  
Patrick Even ◽  
Benoit Viollet
Keyword(s):  
Lipid Metabolism ◽  
De Novo ◽  
Fat Oxidation ◽  
De Novo Lipogenesis ◽  
Acid Oxidation ◽  
Ampk Activation ◽  
Hepatic Lipid ◽  
Adenoviral Delivery ◽  
Body Production

The energy sensor AMP-activated protein kinase (AMPK) is a key player in the control of energy metabolism. AMPK regulates hepatic lipid metabolism through the phosphorylation of its well-recognized downstream target acetyl CoA carboxylase (ACC). Although AMPK activation is proposed to lower hepatic triglyceride (TG) content via the inhibition of ACC to cause inhibition of de novo lipogenesis and stimulation of fatty acid oxidation (FAO), its contribution to the inhibition of FAO in vivo has been recently questioned. We generated a mouse model of AMPK activation specifically in the liver, achieved by expression of a constitutively active AMPK using adenoviral delivery. Indirect calorimetry studies revealed that liver-specific AMPK activation is sufficient to induce a reduction in the respiratory exchange ratio and an increase in FAO rates in vivo. This led to a more rapid metabolic switch from carbohydrate to lipid oxidation during the transition from fed to fasting. Finally, mice with chronic AMPK activation in the liver display high fat oxidation capacity evidenced by increased [C14]-palmitate oxidation and ketone body production leading to reduced hepatic TG content and body adiposity. Our findings suggest a role for hepatic AMPK in the remodeling of lipid metabolism between the liver and adipose tissue.

scholarly journals Short-Term Caloric Restriction Attenuates Obesity-Induced Pro-inflammatory Response in Male Rhesus Macaques

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 511 ◽  
Author(s):  
Hollis Wright ◽  
Mithila Handu ◽  
Allen Jankeel ◽  
Ilhem Messaoudi ◽  
Oleg Varlamov
Keyword(s):  
Inflammatory Response ◽  
Caloric Restriction ◽  
De Novo ◽  
Rhesus Macaques ◽  
De Novo Lipogenesis ◽  
Transcriptional Analysis ◽  
Blood Monocytes ◽  
Short Term ◽  
Adipocyte Hypertrophy ◽  
Male Rhesus

White adipose tissue (WAT) hypertrophy is an essential hallmark of obesity and is associated with the activation of resident immune cells. While the benefits of caloric restriction (CR) on health span are generally accepted, its effects on WAT physiology are not well understood. We previously demonstrated that short-term CR reverses obesity in male rhesus macaques exposed to a high-fat Western-style diet (WSD). Here, we analyzed subcutaneous WAT biopsies collected from this cohort of animals before and after WSD and following CR. This analysis showed that WSD induced adipocyte hypertrophy and inhibited β-adrenergic-simulated lipolysis. CR reversed adipocyte hypertrophy, but WAT remained insensitive to β-adrenergic agonist stimulation. Whole-genome transcriptional analysis revealed that β3-adrenergic receptor and de novo lipogenesis genes were downregulated by WSD and remained downregulated after CR. In contrast, WSD-induced pro-inflammatory gene expression was effectively reversed by CR. Furthermore, peripheral blood monocytes isolated during the CR period exhibited a significant reduction in the production of pro-inflammatory cytokines compared to those obtained after WSD. Collectively, this study demonstrates that short-term CR eliminates an obesity-induced pro-inflammatory response in WAT and peripheral monocytes.

scholarly journals Hepatic Transcriptomics Reveals that Lipogenesis Is a Key Signaling Pathway in Isocitrate Dehydrogenase 2 Deficient Mice

Genes ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 728
Author(s):  
Jeong Hoon Pan ◽  
Jingsi Tang ◽  
Mersady C. Redding ◽  
Kaleigh E. Beane ◽  
Cara L. Conner ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Isocitrate Dehydrogenase ◽  
De Novo ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Tca Cycle ◽  
De Novo Lipogenesis ◽  
Oxidative Decarboxylation ◽  
Qpcr Analysis ◽  
Isocitrate Dehydrogenase 2 ◽  
Mice Liver

Mitochondrial nicotinamide adenine dinucleotide phosphate (NADP+)-dependent isocitrate dehydrogenase (IDH2) plays a key role in the intermediary metabolism and energy production via catalysing oxidative decarboxylation of isocitrate to α-ketoglutarate in the tricarboxylic acid (TCA) cycle. Despite studies reporting potential interlinks between IDH2 and various diseases, there is lack of effort to comprehensively characterize signature(s) of IDH2 knockout (IDH2 KO) mice. A total of 6583 transcripts were identified from both wild-type (WT) and IDH2 KO mice liver tissues. Afterwards, 167 differentially expressed genes in the IDH2 KO group were short-listed compared to the WT group based on our criteria. The online bioinformatic analyses indicated that lipid metabolism is the most significantly influenced metabolic process in IDH2 KO mice. Moreover, the TR/RXR activation pathway was predicted as the top canonical pathway significantly affected by IDH2 KO. The key transcripts found in the bioinformatic analyses were validated by qPCR analysis, corresponding to the transcriptomics results. Further, an additional qPCR analysis confirmed that IDH2 KO caused a decrease in hepatic de novo lipogenesis via the activation of the fatty acid β-oxidation process. Our unbiased transcriptomics approach and validation experiments suggested that IDH2 might play a key role in homeostasis of lipid metabolism.

scholarly journals Beneficial Effects of Bariatric Surgery-Induced by Weight Loss on the Proteome of Abdominal Subcutaneous Adipose Tissue

2020 ◽  
Vol 9 (1) ◽  
pp. 213
Author(s):  
Bárbara María Varela-Rodríguez ◽  
Paula Juiz-Valiña ◽  
Luis Varela ◽  
Elena Outeiriño-Blanco ◽  
Susana Belén Bravo ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Positive Impact ◽  
De Novo Lipogenesis ◽  
Beneficial Effects ◽  
Proteomic Approach ◽  
Subcutaneous Adipose

Bariatric surgery (BS) is the most effective treatment for obesity and has a positive impact on cardiometabolic risk and in the remission of type 2 diabetes. Following BS, the majority of fat mass is lost from the subcutaneous adipose tissue depot (SAT). However, the changes in this depot and functions and as well as its relative contribution to the beneficial effects of this surgery are still controversial. With the aim of studying altered proteins and molecular pathways in abdominal SAT (aSAT) after body weight normalization induced by BS, we carried out a proteomic approach sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis. These results were complemented by Western blot, electron microscopy and RT-qPCR. With all of the working tools mentioned, we confirmed that after BS, up-regulated proteins were associated with metabolism, the citric acid cycle and respiratory electron transport, triglyceride catabolism and metabolism, formation of ATP, pyruvate metabolism, glycolysis/gluconeogenesis and thermogenesis among others. In contrast, proteins with decreased values are part of the biological pathways related to the immune system. We also confirmed that obesity caused a significant decrease in mitochondrial density and coverage, which was corrected by BS. Together, these findings reveal specific molecular mechanisms, genes and proteins that improve adipose tissue function after BS characterized by lower inflammation, increased glucose uptake, higher insulin sensitivity, higher de novo lipogenesis, increased mitochondrial function and decreased adipocyte size.

scholarly journals SLC25A1 promotes tumor growth and survival by reprogramming energy metabolism in colorectal cancer

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Ying Yang ◽  
Jiaxing He ◽  
Bo Zhang ◽  
Zhansheng Zhang ◽  
Guozhan Jia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lipid Metabolism ◽  
Energy Metabolism ◽  
Cell Apoptosis ◽  
De Novo ◽  
Lipid Synthesis ◽  
Growth And Survival ◽  
Metabolism Regulation

AbstractAbnormal lipid metabolism has been commonly observed in various human cancers, including colorectal cancer (CRC). The mitochondrial citrate carrier SLC25A1 (also known as mitochondrial citrate/isocitrate carrier, CIC), has been shown to play an important role in lipid metabolism regulation. Our bioinformatics analysis indicated that SLC25A1 was markedly upregulated in CRC. However, the role of SLC25A1 in the pathogenesis and aberrant lipid metabolism in CRC remain unexplored. Here, we found that SLC25A1 expression was significantly increased in tumor samples of CRC as compared with paired normal samples, which is associated with poor survival in patients with CRC. Knockdown of SLC25A1 significantly inhibited the growth of CRC cells by suppressing the progression of the G1/S cell cycle and inducing cell apoptosis both in vitro and in vivo, whereas SLC25A1 overexpression suppressed the malignant phenotype. Additionally, we demonstrated that SLC25A1 reprogrammed energy metabolism to promote CRC progression through two mechanisms. Under normal conditions, SLC25A1 increased de novo lipid synthesis to promote CRC growth. During metabolic stress, SLC25A1 increased oxidative phosphorylation (OXPHOS) to protect protects CRC cells from energy stress-induced cell apoptosis. Collectively, SLC25A1 plays a pivotal role in the promotion of CRC growth and survival by reprogramming energy metabolism. It could be exploited as a novel diagnostic marker and therapeutic target in CRC.

scholarly journals DHT Causes Liver Steatosis via Transcriptional Regulation of SCAP in Lean female Mice

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A807-A807
Author(s):  
Stanley Andrisse ◽  
Jessie Myer ◽  
Dilip “Bobby” Bogle ◽  
Nicole Eregha ◽  
Taylor Lofton
Keyword(s):  
Lipid Metabolism ◽  
Protein Expression ◽  
Low Dose ◽  
De Novo ◽  
Polycystic Ovary ◽  
Liver Steatosis ◽  
De Novo Lipogenesis ◽  
Alcoholic Fatty Liver ◽  
Female Mice ◽  
Real Time Quantitative Pcr

Abstract Hyperandrogenemia (HA) and insulin resistance are hallmarks of polycystic ovary syndrome (PCOS). These hallmarks are also integral elements of non-alcoholic fatty liver disease (NALFD). Administering low dose dihydrotestosterone (DHT) induced a lean PCOS-like female mouse model. The molecular mechanism of HA-induced NAFLD has not been determined. We hypothesized that low dose DHT would interrupt hepatic lipid metabolism leading to NAFLD. We extracted white adipose tissue (WAT), liver, and skeletal muscle from control and low dose DHT female mice; and performed histological and biochemical lipid profiles, Western blot, immunoprecipitation, chromatin immunoprecipitation, and real-time quantitative PCR analyses. DHT lowered the 65 kD form of cytosolic SREBP1 in the liver and WAT compared to controls. However, DHT did not alter the levels of the active and inactive forms of SREBP2 in the liver and WAT. DHT increased SCAP protein expression and SCAP-SREBP1 binding via AR binding to intron-8 of SCAP leading to increased SCAP mRNA. FAS mRNA and protein expression was increased in liver of DHT mice. p-ACC levels were unaltered in liver but decreased in WAT. Other lipid metabolism pathways were examined in liver and WAT, but no changes were observed. Our findings suggest that DHT increased de novo lipogenic proteins resulting in increased NAFLD via regulation of SREBP1 in liver. We show that in the presence of DHT the SCAP-SREBP1 interaction is elevated leading to increased nuclear SREBP1 resulting in increased de novo lipogenesis. We propose that the mechanism of action is increased AR binding to an ARE in SCAP intron-8.

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