Lipid Metabolism, Adipogenesis and Fat Tissue Metabolism: Gene Regulation

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (15 June 2022) | Viewed by 32672

Special Issue Editors


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Guest Editor
Department of Animal Physiology, Biochemistry and Biostructure, Poznan University of Life Sciences, 60-637 Poznań, Poland
Interests: adipose tissue; cell biology; diabetes; metabolism; obesity
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Animal Physiology, Biochemistry and Biostructure, Poznan University of Life Sciences, 60-637 Poznań, Poland
Interests: diabetes; obesity; fat tissue; pancreas; liver; muscle; metabolic syndrome; cell biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We would like to kindly invite you to participate in this Special Issue: Lipid Metabolism, Adipogenesis, and Fat Tissue Metabolism: Gene Regulation in the MDPI journal Genes.

Lipid metabolism plays a pivotal role in maintaining energy homeostasis in health and disease. Impaired lipid metabolism is a hallmark of numerous metabolic diseases, such as obesity, metabolic syndrome, or type 2 diabetes mellitus. One of the most important organs involved in controlling the lipid metabolism is the white and brown adipose tissue. White adipocytes serve as energy storage but also produce and release metabolic and hormonal signals contributing to modulation of energy homeostasis and whole-body metabolism. There is growing evidence indicating that white fat cells’ excess and dysfunction play a prominent role in the development of obesity and obesity-associated abnormalities. By contrast, brown and bridge adipocytes promote energy expenditure and negative energy balance, improve insulin sensitivity, and protect against obesity. In this Special Issue, we are inviting original works and review articles dedicated to improving the knowledge related to molecular mechanisms regulating lipid metabolism, adipogenesis, and mature fat cell functions. Especially, we are interested in contributions related to gene-regulated mechanisms responsible for lipid metabolism regulation, fat tissue formation, and the functions of white, brown, and bridge adipocytes. We will consider for evaluation all manuscripts related to the transcriptional and epigenetic regulation of lipid metabolism and fat tissue biology.

Dr. Marek Skrzypski
Dr. Paweł A. Kołodziejski
Guest Editors

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Keywords

  • Lipid metabolism
  • Adipocytes
  • Adipogenesis
  • Gene expression
  • Energy homeostasis

Published Papers (9 papers)

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Editorial

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2 pages, 182 KiB  
Editorial
Special Issue: Lipid Metabolism, Adipogenesis and Fat Tissue Metabolism: Gene Regulation
by Marek Skrzypski and Paweł A. Kołodziejski
Genes 2023, 14(5), 1121; https://doi.org/10.3390/genes14051121 - 22 May 2023
Cited by 1 | Viewed by 1304
Abstract
Lipid metabolism is pivotal in controlling energy homeostasis [...] Full article

Research

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15 pages, 3974 KiB  
Article
Spexin Promotes the Proliferation and Differentiation of C2C12 Cells In Vitro—The Effect of Exercise on SPX and SPX Receptor Expression in Skeletal Muscle In Vivo
by Natalia Leciejewska, Ewa Pruszyńska-Oszmałek, Karolina Mielnik, Maciej Głowacki, Tomasz P. Lehmann, Maciej Sassek, Bartosz Gawęda, Dawid Szczepankiewicz, Krzysztof W. Nowak and Paweł A. Kołodziejski
Genes 2022, 13(1), 81; https://doi.org/10.3390/genes13010081 - 28 Dec 2021
Cited by 11 | Viewed by 2765
Abstract
SPX (spexin) and its receptors GalR2 and GalR3 (galanin receptor subtype 2 and galanin receptor subtype 3) play an important role in the regulation of lipid and carbohydrate metabolism in human and animal fat tissue. However, little is still known about the role [...] Read more.
SPX (spexin) and its receptors GalR2 and GalR3 (galanin receptor subtype 2 and galanin receptor subtype 3) play an important role in the regulation of lipid and carbohydrate metabolism in human and animal fat tissue. However, little is still known about the role of this peptide in the metabolism of muscle. The aim of this study was to determine the impact of SPX on the metabolism, proliferation and differentiation of the skeletal muscle cell line C2C12. Moreover, we determined the effect of exercise on the SPX transduction pathway in mice skeletal muscle. We found that increased SPX, acting via GalR2 and GalR3 receptors, and ERK1/2 phosphorylation stimulated the proliferation of C2C12 cells (p < 0.01). We also noted that SPX stimulated the differentiation of C2C12 by increasing mRNA and protein levels of differentiation markers Myh, myogenin and MyoD (p < 0.01). SPX consequently promoted myoblast fusion into the myotubule (p < 0.01). Moreover, we found that, in the first stage (after 2 days) of myocyte differentiation, GalR2 and GalR3 were involved, whereas in the last stage (day six), the effect of SPX was mediated by the GalR3 isoform. We also noted that exercise stimulated SPX and GalR2 expression in mice skeletal muscle as well as an increase in SPX concentration in blood serum. These new insights may contribute to a better understanding of the role of SPX in the metabolism of skeletal muscle. Full article
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13 pages, 2692 KiB  
Article
Adropin Slightly Modulates Lipolysis, Lipogenesis and Expression of Adipokines but Not Glucose Uptake in Rodent Adipocytes
by Mariami Jasaszwili, Ewa Pruszyńska-Oszmałek, Tatiana Wojciechowicz, Mathias Z. Strowski, Krzysztof W. Nowak and Marek Skrzypski
Genes 2021, 12(6), 914; https://doi.org/10.3390/genes12060914 - 13 Jun 2021
Cited by 8 | Viewed by 2653
Abstract
Adropin is a peptide hormone which modulates energy homeostasis and metabolism. In animals with diet-induced obesity, adropin attenuates adiposity and improves lipid and glucose homeostasis. Adropin promotes the proliferation of rodent white preadipocytes and suppresses their differentiation into adipocytes. By contrast, the effects [...] Read more.
Adropin is a peptide hormone which modulates energy homeostasis and metabolism. In animals with diet-induced obesity, adropin attenuates adiposity and improves lipid and glucose homeostasis. Adropin promotes the proliferation of rodent white preadipocytes and suppresses their differentiation into adipocytes. By contrast, the effects of adropin on mature white adipocytes are unknown. Therefore, we aimed to evaluate the effects of adropin on lipolysis, lipogenesis and glucose uptake in white rodent adipocytes. We assessed the effects of adropin on the mRNA expression of adiponectin, resistin and visfatin. White preadipocytes were isolated from male Wistar rats. Differentiated 3T3-L1 cells were used as a surrogate model of white adipocytes. Lipolysis was measured by the evaluation of glycerol and free fatty acid secretion using colorimetric kits. The effects of adropin on lipogenesis and glucose uptake were measured using radioactive-labelled glucose. The expression of adipokine mRNA was studied using real-time PCR. Our results show that adropin slightly promotes lipolysis in rat adipocytes and 3T3-L1 cells. Adropin suppresses lipogenesis in rat adipocytes without influencing glucose uptake. In addition, adropin stimulates adiponectin mRNA expression and suppresses the expression of resistin and visfatin. These results indicate that adropin may be involved in controlling lipid metabolism and adipokine expression in white rodent adipocytes. Full article
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14 pages, 4189 KiB  
Article
ANGPTL3 Variants Associate with Lower Levels of Irisin and C-Peptide in a Cohort of Arab Individuals
by Muath Alanbaei, Mohamed Abu-Farha, Prashantha Hebbar, Motasem Melhem, Betty S. Chandy, Emil Anoop, Preethi Cherian, Irina Al-Khairi, Fadi Alkayal, Fahd Al-Mulla, Jehad Abubaker and Thangavel Alphonse Thanaraj
Genes 2021, 12(5), 755; https://doi.org/10.3390/genes12050755 - 17 May 2021
Cited by 1 | Viewed by 2117
Abstract
ANGPTL3 is an important regulator of lipid metabolism. Its inhibition in people with hypercholesteremia reduces plasma lipid levels dramatically. Genome-wide association studies have associated ANGPTL3 variants with lipid traits. Irisin, an exercise-modulated protein, has been associated with lipid metabolism. Intracellular accumulation of lipids [...] Read more.
ANGPTL3 is an important regulator of lipid metabolism. Its inhibition in people with hypercholesteremia reduces plasma lipid levels dramatically. Genome-wide association studies have associated ANGPTL3 variants with lipid traits. Irisin, an exercise-modulated protein, has been associated with lipid metabolism. Intracellular accumulation of lipids impairs insulin action and contributes to metabolic disorders. In this study, we evaluate the impact of ANGPTL3 variants on levels of irisin and markers associated with lipid metabolism and insulin resistance. ANGPTL3 rs1748197 and rs12130333 variants were genotyped in a cohort of 278 Arab individuals from Kuwait. Levels of irisin and other metabolic markers were measured by ELISA. Significance of association signals was assessed using Bonferroni-corrected p-values and empirical p-values. The study variants were significantly associated with low levels of c-peptide and irisin. Levels of c-peptide and irisin were mediated by interaction between carrier genotypes (GA + AA) at rs1748197 and measures of IL13 and TG, respectively. While levels of c-peptide and IL13 were directly correlated in individuals with the reference genotype, they were inversely correlated in individuals with the carrier genotype. Irisin correlated positively with TG and was strong in individuals with carrier genotypes. These observations illustrate ANGPTL3 as a potential link connecting lipid metabolism, insulin resistance and cardioprotection. Full article
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16 pages, 335 KiB  
Article
Epigenetic Regulation of Processes Related to High Level of Fibroblast Growth Factor 21 in Obese Subjects
by Teresa Płatek, Anna Polus, Joanna Góralska, Urszula Raźny, Agnieszka Dziewońska, Agnieszka Micek, Aldona Dembińska-Kieć, Bogdan Solnica and Małgorzata Malczewska-Malec
Genes 2021, 12(2), 307; https://doi.org/10.3390/genes12020307 - 21 Feb 2021
Cited by 9 | Viewed by 2681
Abstract
We hypothesised that epigenetics may play an important role in mediating fibroblast growth factor 21 (FGF21) resistance in obesity. We aimed to evaluate DNA methylation changes and miRNA pattern in obese subjects associated with high serum FGF21 levels. The study included 136 participants [...] Read more.
We hypothesised that epigenetics may play an important role in mediating fibroblast growth factor 21 (FGF21) resistance in obesity. We aimed to evaluate DNA methylation changes and miRNA pattern in obese subjects associated with high serum FGF21 levels. The study included 136 participants with BMI 27–45 kg/m2. Fasting FGF21, glucose, insulin, GIP, lipids, adipokines, miokines and cytokines were measured and compared in high serum FGF21 (n = 68) group to low FGF21 (n = 68) group. Human DNA Methylation Microarrays were analysed in leukocytes from each group (n = 16). Expression of miRNAs was evaluated using quantitative PCR-TLDA. The study identified differentially methylated genes in pathways related to glucose transport, insulin secretion and signalling, lipid transport and cellular metabolism, response to nutrient levels, thermogenesis, browning of adipose tissue and bone mineralisation. Additionally, it detected transcription factor genes regulating FGF21 and fibroblast growth factor receptor and vascular endothelial growth factor receptor pathways regulation. Increased expression of hsa-miR-875-5p and decreased expression of hsa-miR-133a-3p, hsa-miR-185-5p and hsa-miR-200c-3p were found in the group with high serum FGF21. These changes were associated with high FGF21, VEGF and low adiponectin serum levels. Our results point to a significant role of the epigenetic regulation of genes involved in metabolic pathways related to FGF21 action. Full article
19 pages, 3251 KiB  
Article
Expression Signatures of microRNAs and Their Targeted Pathways in the Adipose Tissue of Chickens during the Transition from Embryonic to Post-Hatch Development
by Julie A. Hicks and Hsiao-Ching Liu
Genes 2021, 12(2), 196; https://doi.org/10.3390/genes12020196 - 29 Jan 2021
Cited by 3 | Viewed by 2750
Abstract
As the chick transitions from embryonic to post-hatching life, its metabolism must quickly undergo a dramatic switch in its major energy source. The chick embryo derives most of its energy from the yolk, a lipid-rich/carbohydrate-poor source. Upon hatching, the chick’s metabolism must then [...] Read more.
As the chick transitions from embryonic to post-hatching life, its metabolism must quickly undergo a dramatic switch in its major energy source. The chick embryo derives most of its energy from the yolk, a lipid-rich/carbohydrate-poor source. Upon hatching, the chick’s metabolism must then be able to utilize a lipid-poor/carbohydrate-rich source (feed) as its main form of energy. We recently found that a number of hepatically-expressed microRNAs (miRNAs) help facilitate this shift in metabolic processes in the chick liver, the main site of lipogenesis. While adipose tissue was initially thought to mainly serve as a lipid storage site, it is now known to carry many metabolic, endocrine, and immunological functions. Therefore, it would be expected that adipose tissue is also an important factor in the metabolic switch. To that end, we used next generation sequencing (NGS) and real-time quantitative PCR (RT-qPCR) to generate miRNome and transcriptome signatures of the adipose tissue during the transition from late embryonic to early post-hatch development. As adipose tissue is well known to produce inflammatory and other immune factors, we used SPF white leghorns to generate the initial miRNome and transcriptome signatures to minimize complications from external factors (e.g., pathogenic infections) and ensure the identification of bona fide switch-associated miRNAs and transcripts. We then examined their expression signatures in the adipose tissue of broilers (Ross 708). Using E18 embryos as representative of pre-switching metabolism and D3 chicks as a representative of post-switching metabolism, we identified a group of miRNAs which work concordantly to regulate a diverse but interconnected group of developmental, immune and metabolic processes in the adipose tissue during the metabolic switch. Network mapping suggests that during the first days post-hatch, despite the consumption of feed, the chick is still heavily reliant upon adipose tissue lipid stores for energy production, and is not yet efficiently using their new energy source for de novo lipid storage. A number of core master regulatory pathways including, circadian rhythm transcriptional regulation and growth hormone (GH) signaling, likely work in concert with miRNAs to maintain an essential balance between adipogenic, lipolytic, developmental, and immunological processes in the adipose tissue during the metabolic switch. Full article
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16 pages, 2716 KiB  
Article
Metabolic Differences between Subcutaneous and Visceral Adipocytes Differentiated with an Excess of Saturated and Monounsaturated Fatty Acids
by Małgorzata Małodobra-Mazur, Aneta Cierzniak, Dorota Pawełka, Krzysztof Kaliszewski, Jerzy Rudnicki and Tadeusz Dobosz
Genes 2020, 11(9), 1092; https://doi.org/10.3390/genes11091092 - 18 Sep 2020
Cited by 24 | Viewed by 4506
Abstract
Obesity is a major health problem in highly industrialized countries. High-fat diet (HFD) is one of the most common causes of obesity and obesity-related disorders. There are considerable differences between fat depots and the corresponding risks of metabolic disorders. We investigated the various [...] Read more.
Obesity is a major health problem in highly industrialized countries. High-fat diet (HFD) is one of the most common causes of obesity and obesity-related disorders. There are considerable differences between fat depots and the corresponding risks of metabolic disorders. We investigated the various effects of an excess of fatty acids (palmitic 16:0, stearic 18:0, and oleic acids 18:1n−9) on adipogenesis of subcutaneous- and visceral-derived mesenchymal stem cells (MSCs) and phenotypes of mature adipocytes. MSCs of white adipose tissue were acquired from adipose tissue biopsies obtained from subcutaneous and visceral fat depots from patients undergoing abdominal surgery. The MSCs were extracted and differentiated in vitro with the addition of fatty acids. Oleic acid stimulated adipogenesis, resulting in higher lipid content and larger adipocytes. Furthermore, oleic acid stimulated adipogenesis by increasing the expression of CCAAT enhancer binding protein β (CEBPB) and peroxisome proliferator activated receptor γ (PPARG). All of the examined fatty acids attenuated the insulin-signaling pathway and radically reduced glucose uptake following insulin stimulation. Visceral adipose tissue was shown to be more prone to generate inflammatory stages. The subcutaneous adipose tissue secreted a greater quantity of adipokines. To summarize, oleic acid showed the strongest effect on adipogenesis. Furthermore, all of the examined fatty acids attenuated insulin signaling and secretion of cytokines and adipokines. Full article
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Review

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22 pages, 4729 KiB  
Review
The Role of Peptide Hormones Discovered in the 21st Century in the Regulation of Adipose Tissue Functions
by Paweł A. Kołodziejski, Ewa Pruszyńska-Oszmałek, Tatiana Wojciechowicz, Maciej Sassek, Natalia Leciejewska, Mariami Jasaszwili, Maria Billert, Emilian Małek, Dawid Szczepankiewicz, Magdalena Misiewicz-Mielnik, Iwona Hertig, Leszek Nogowski, Krzysztof W. Nowak, Mathias Z. Strowski and Marek Skrzypski
Genes 2021, 12(5), 756; https://doi.org/10.3390/genes12050756 - 17 May 2021
Cited by 21 | Viewed by 5641
Abstract
Peptide hormones play a prominent role in controlling energy homeostasis and metabolism. They have been implicated in controlling appetite, the function of the gastrointestinal and cardiovascular systems, energy expenditure, and reproduction. Furthermore, there is growing evidence indicating that peptide hormones and their receptors [...] Read more.
Peptide hormones play a prominent role in controlling energy homeostasis and metabolism. They have been implicated in controlling appetite, the function of the gastrointestinal and cardiovascular systems, energy expenditure, and reproduction. Furthermore, there is growing evidence indicating that peptide hormones and their receptors contribute to energy homeostasis regulation by interacting with white and brown adipose tissue. In this article, we review and discuss the literature addressing the role of selected peptide hormones discovered in the 21st century (adropin, apelin, elabela, irisin, kisspeptin, MOTS-c, phoenixin, spexin, and neuropeptides B and W) in controlling white and brown adipogenesis. Furthermore, we elaborate how these hormones control adipose tissue functions in vitro and in vivo. Full article
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30 pages, 2881 KiB  
Review
The Role of Lipid Sensing Nuclear Receptors (PPARs and LXR) and Metabolic Lipases in Obesity, Diabetes and NAFLD
by Emmanuel D. Dixon, Alexander D. Nardo, Thierry Claudel and Michael Trauner
Genes 2021, 12(5), 645; https://doi.org/10.3390/genes12050645 - 26 Apr 2021
Cited by 44 | Viewed by 6722
Abstract
Obesity and type 2 diabetes mellitus (T2DM) are metabolic disorders characterized by metabolic inflexibility with multiple pathological organ manifestations, including non-alcoholic fatty liver disease (NAFLD). Nuclear receptors are ligand-dependent transcription factors with a multifaceted role in controlling many metabolic activities, such as regulation [...] Read more.
Obesity and type 2 diabetes mellitus (T2DM) are metabolic disorders characterized by metabolic inflexibility with multiple pathological organ manifestations, including non-alcoholic fatty liver disease (NAFLD). Nuclear receptors are ligand-dependent transcription factors with a multifaceted role in controlling many metabolic activities, such as regulation of genes involved in lipid and glucose metabolism and modulation of inflammatory genes. The activity of nuclear receptors is key in maintaining metabolic flexibility. Their activity depends on the availability of endogenous ligands, like fatty acids or oxysterols, and their derivatives produced by the catabolic action of metabolic lipases, most of which are under the control of nuclear receptors. For example, adipose triglyceride lipase (ATGL) is activated by peroxisome proliferator-activated receptor γ (PPARγ) and conversely releases fatty acids as ligands for PPARα, therefore, demonstrating the interdependency of nuclear receptors and lipases. The diverse biological functions and importance of nuclear receptors in metabolic syndrome and NAFLD has led to substantial effort to target them therapeutically. This review summarizes recent findings on the roles of lipases and selected nuclear receptors, PPARs, and liver X receptor (LXR) in obesity, diabetes, and NAFLD. Full article
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