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New Updates in Adipocytes and Adipose Tissue

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A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 21021

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Dr. Kristóf Endre Károly

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Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Interests: brown adipose tissue; thermogenesis; beige adipocytes; irisin; autophagy; adipokines; interleukin-6
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Dr. Éva Csősz

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Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
Interests: proteomics; metabolomics; serum metabolites; obesity; insulin resistance; system biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Obesity is one of the major risk factors of insulin resistance, metabolic syndrome, coronary heart disease, and cancer, which are all leading causes of mortality today. Although the combined prevalence of overweight and obesity has increased continuously up to 40-50% in most developed countries, effective therapeutic approaches, including behavioral therapy, pharmacotherapy, or bariatric surgery, against this threat are very limited. Adipose tissue is a complex organ with profound effects on the homeostasis of the entire body. White adipocytes function as long-term energy storage by accumulating a single large lipid vacuole, which is surrounded by a thin rim of cytoplasm that contains only small amounts of mitochondria, and produce metabolites, signaling lipids, and secretes protein factors (adipokines). Brown and beige adipocytes accumulate numerous small lipid droplets in a multilocular arrangement, contain a large amount of mitochondria-rich cytoplasm, and convert glucose and fatty acids into heat. The production of adipocyte-derived factors changes under different nutritional and pathological conditions that contribute to the pathophysiology of several comorbidities. This Special Issue focuses on metabolic changes and novel molecular pathways observed in obesity with a high emphasis on adipose tissues that can be targeted in the fight against obesity and metabolic syndrome.

Dr. Kristóf Endre Károly
Dr. Éva Csősz
Guest Editors

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Keywords

adipose tissue
obesity
inflammation
thermogenesis
adipokines
insulin resistance
fat
Adipogenesis

Published Papers (10 papers)

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Research

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28 pages, 10465 KiB

Open AccessArticle

Characterizing 3T3-L1 MBX Adipocyte Cell Differentiation Maintained with Fatty Acids as an In Vitro Model to Study the Effects of Obesity

by Noshin Mubtasim and Lauren Gollahon

Life 2023, 13(8), 1712; https://doi.org/10.3390/life13081712 - 09 Aug 2023

Cited by 1 | Viewed by 1813

Abstract

The increasing prevalence of obesity has prompted intensive research into understanding its role in pathogenesis and designing appropriate treatments. To determine the signals generated from the interaction of fat cells with a target organ, a reliable white adipocyte model in vitro is needed. Differentiated fibroblasts are the most extensively studied using in vitro cell models of white adipocytes. However, it can be argued that differentiated fibroblasts minimally recapitulate the consequences of obesity. Here, we describe 3T3-L1 MBX cells as a culture model for studying obese adipocytes and their effects. Differentiation of 3T3-L1 MBX cells was at first optimized and then maintained in the presence of fatty acids cocktail combination to induce the obese condition. Lipid accumulation and adipokine secretion profiles were analyzed. Results showed that fatty acid-maintained, differentiated 3T3-L1 MBX cells had significantly greater accumulation of lipids and significant changes in the adipokine secretions in comparison to differentiated 3T3-L1 MBX cells maintained in medium without fatty acids. To elucidate the molecular changes associated with adipogenesis and lipid accumulation profile of 3T3-L1 MBX cells, we have also explored the expression of some of the regulatory proteins related to the development and maintenance of adipocytes from the preadipocyte lineage. Full article

(This article belongs to the Special Issue New Updates in Adipocytes and Adipose Tissue)

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15 pages, 2413 KiB

Open AccessArticle

Eicosapentaenoic Acid Induces the Inhibition of Adipogenesis by Reducing the Effect of PPARγ Activator and Mediating PKA Activation and Increased COX-2 Expression in 3T3-L1 Cells at the Differentiation Stage

by Michael N. N. Nartey, Hidehisa Shimizu, Hikaru Sugiyama, Manami Higa, Pinky Karim Syeda, Kohji Nishimura, Mitsuo Jisaka and Kazushige Yokota

Life 2023, 13(8), 1704; https://doi.org/10.3390/life13081704 - 08 Aug 2023

Viewed by 1145

Abstract

Obesity has received increasing attention in recent years because it is a factor in the development of non-communicable diseases. The current study aimed to analyze how representative fatty acids (FAs) such as palmitic acid, stearic acid, oleic acid, α-linolenic acid (ALA), and eicosapentaenoic acid (EPA) affected adipogenesis when/if introduced at the differentiation stage of 3T3-L1 cell culture. These FAs are assumed to be potentially relevant to the progression or prevention of obesity. EPA added during the differentiation stage reduced intracellular triacylglycerol (TAG) accumulation, as well as the expression of the established adipocyte-specific marker genes, during the maturation stage. However, no other FAs inhibited intracellular TAG accumulation. Coexistence of Δ¹²-prostaglandin J₂, a peroxisome proliferator-activated receptor γ activator, with EPA during the differentiation stage partially attenuated the inhibitory effect of EPA on intracellular TAG accumulation. EPA increased cyclooxygenase-2 (COX-2) expression and protein kinase A (PKA) activity at the differentiation stage, which could explain the inhibitory actions of EPA. Taken together, exposure of preadipocytes to EPA only during the differentiation stage may be sufficient to finally reduce the mass of white adipose tissue through increasing COX-2 expression and PKA activity. Full article

(This article belongs to the Special Issue New Updates in Adipocytes and Adipose Tissue)

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21 pages, 10905 KiB

Open AccessArticle

Constitutive Serotonin Tone as a Modulator of Brown Adipose Tissue Thermogenesis: A Rat Study

by Maja Kesić, Petra Baković, Vladimir Farkaš, Robert Bagarić, Darko Kolarić, Jasminka Štefulj and Lipa Čičin-Šain

Life 2023, 13(7), 1436; https://doi.org/10.3390/life13071436 - 25 Jun 2023

Viewed by 1155

Abstract

Brown adipose tissue (BAT), an important regulator of thermogenic and metabolic processes, is considered a promising target to combat metabolic disorders. The neurotransmitter and hormone serotonin (5HT) is a major modulator of energy homeostasis, with its central and peripheral pools acting in opposing ways. To better understand how individual variations in 5HT homeostasis influence the thermogenic functionality of BAT, we used a rat model consisting of two sublines with constitutively increased (high-5HT) or decreased (low-5HT) whole-body 5HT tone, developed by selective breeding for platelet 5HT parameters. We have shown that animals with constitutively low 5HT activity maintained at a standard housing temperature (22 °C) have greater interscapular BAT (iBAT) mass and higher iBAT metabolic activity (as evidenced by measurements of iBAT temperature and glucose uptake), accompanied by increased iBAT mRNA expression of key thermogenic genes, compared to animals with high 5HT tone. In response to further thermogenic challenges—intermittent cold exposure or treatment with a β₃-adrenergic agonist—5HT sublines show several functional and molecular differences linking constitutively low endogenous 5HT tone to higher BAT activity/capacity. Overall, the results support a role of 5-HT in the control of BAT thermogenesis They also suggest that individuals with lower 5HT activity may be more sensitive to β3-adrenergic drugs. Full article

(This article belongs to the Special Issue New Updates in Adipocytes and Adipose Tissue)

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14 pages, 3939 KiB

Open AccessArticle

Micro-Current Stimulation Can Modulate the Adipogenesis Process by Regulating the Insulin Signaling Pathway in 3T3-L1 Cells and ob/ob Mice

by Hana Lee, Jin-Ho Lee, Doyong Kim, Donghyun Hwang, Minjoo Lee, Halim Chung, Tack-Joong Kim and Han Sung Kim

Life 2023, 13(2), 404; https://doi.org/10.3390/life13020404 - 01 Feb 2023

Cited by 3 | Viewed by 1765

Abstract

Obesity is a disease in which fat is abnormally or excessively accumulated in the body, and many studies have been conducted to overcome it with various techniques. In this study, we evaluated whether micro-current stimulation (MCS) can be applied to prevent obesity by regulating the adipogenesis through 3T3-L1 cells and ob/ob mice. To specify the intensity of MCS, Oil Red O staining was conducted with various intensities of MCS. Based on these, subsequent experiments used 200 and 400 μA for the intensity of MCS. The expressions of insulin signaling pathway-related proteins, including phosphorylation of IGF-1 and IR, were decreased in all MCS groups, and in turn, downstream signals such as Akt and ERK were decreased. In addition, MCS reduced the nucleus translocation of PPAR-γ and decreased the protein expression of C/EBP-α. In the ob/ob mouse model, MCS reduced body weight gain and abdominal adipose tissue volume. In particular, the concentration of triglycerides in serum was also decreased. Taken together, our findings showed that MCS inhibited lipid accumulation by regulating insulin signaling in 3T3-L1, and it was effective at reducing body weight and adipose tissue volume in ob/ob mice. These suggest that MCS may be a useful treatment approach for obesity. Full article

(This article belongs to the Special Issue New Updates in Adipocytes and Adipose Tissue)

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14 pages, 1478 KiB

Open AccessArticle

Prostaglandin D₂ Added during the Differentiation of 3T3-L1 Cells Suppresses Adipogenesis via Dysfunction of D-Prostanoid Receptor P1 and P2

by Michael N. N. Nartey, Mitsuo Jisaka, Pinky Karim Syeda, Kohji Nishimura, Hidehisa Shimizu and Kazushige Yokota

Life 2023, 13(2), 370; https://doi.org/10.3390/life13020370 - 29 Jan 2023

Cited by 1 | Viewed by 1299

Abstract

We previously reported that the addition of prostaglandin, (PG)D₂, and its chemically stable analog, 11-deoxy-11-methylene-PGD₂ (11d-11m-PGD₂), during the maturation phase of 3T3-L1 cells promotes adipogenesis. In the present study, we aimed to elucidate the effects of the addition of PGD₂ or 11d-11m-PGD₂ to 3T3-L1 cells during the differentiation phase on adipogenesis. We found that both PGD₂ and 11d-11m-PGD₂ suppressed adipogenesis through the downregulation of peroxisome proliferator-activated receptor gamma (PPARγ) expression. However, the latter suppressed adipogenesis more potently than PGD₂, most likely because of its higher resistance to spontaneous transformation into PGJ₂ derivatives. In addition, this anti-adipogenic effect was attenuated by the coexistence of an IP receptor agonist, suggesting that the effect depends on the intensity of the signaling from the IP receptor. The D-prostanoid receptors 1 (DP1) and 2 (DP2, also known as a chemoattractant receptor-homologous molecule expressed on Th2 cells) are receptors for PGD₂. The inhibitory effects of PGD₂ and 11d-11m-PGD₂ on adipogenesis were slightly attenuated by a DP2 agonist. Furthermore, the addition of PGD₂ and 11d-11m-PGD₂ during the differentiation phase reduced the DP1 and DP2 expression during the maturation phase. Overall, these results indicated that the addition of PGD₂ or 11d-11m-PGD₂ during the differentiation phase suppresses adipogenesis via the dysfunction of DP1 and DP2. Therefore, unidentified receptor(s) for both molecules may be involved in the suppression of adipogenesis. Full article

(This article belongs to the Special Issue New Updates in Adipocytes and Adipose Tissue)

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16 pages, 1766 KiB

Open AccessArticle

Arachidonic Acid Added during the Differentiation Phase of 3T3-L1 Cells Exerts Anti-Adipogenic Effect by Reducing the Effects of Pro-Adipogenic Prostaglandins

by Michael N. N. Nartey, Mitsuo Jisaka, Pinky Karim Syeda, Kohji Nishimura, Hidehisa Shimizu and Kazushige Yokota

Life 2023, 13(2), 367; https://doi.org/10.3390/life13020367 - 29 Jan 2023

Cited by 2 | Viewed by 1389

Abstract

A linoleic acid (LA) metabolite arachidonic acid (AA) added to 3T3-L1 cells is reported to suppress adipogenesis. The purpose of the present study aimed to clarify the effects of AA added during the differentiation phase, including adipogenesis, the types of prostaglandins (PG)s produced, and the crosstalk between AA and the PGs produced. Adipogenesis was inhibited by AA added, while LA did not. When AA was added, increased PGE₂ and PGF_2α production, unchanged Δ¹²-PGJ₂ production, and reduced PGI₂ production were observed. Since the decreased PGI₂ production was reflected in decreased CCAAT/enhancer-binding protein-β (C/EBPβ) and C/EBPδ expression, we expected that the coexistence of PGI₂ with AA would suppress the anti-adipogenic effects of AA. However, the coexistence of PGI₂ with AA did not attenuate the anti-adipogenic effects of AA. In addition, the results were similar when Δ¹²-PGJ₂ coexisted with AA. Taken together, these results indicated that the metabolism of ingested LA to AA is necessary to inhibit adipogenesis and that exposure of AA to adipocytes during only the differentiation phase is sufficient. As further mechanisms for suppressing adipogenesis, AA was found not only to increase PGE₂ and PGF_2α and decrease PGI₂ production but also to abrogate the pro-adipogenic effects of PGI₂ and Δ¹²-PGJ₂. Full article

(This article belongs to the Special Issue New Updates in Adipocytes and Adipose Tissue)

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13 pages, 1426 KiB

Open AccessArticle

Glycine Effect on the Expression Profile of Orphan Receptors GPR21, GPR26, GPR39, GPR82 and GPR6 in a Model of Inflammation in 3T3-L1 Cells

by Rocío Alejandra Gutiérrez-Rojas, Karla Aidee Aguayo-Cerón, Cruz Vargas-De-León, Sandra Edith Cabrera-Becerra, Julio Cesar Almanza-Pérez, Fengyang Huang, Santiago Villafaña and Rodrigo Romero-Nava

Life 2022, 12(11), 1687; https://doi.org/10.3390/life12111687 - 24 Oct 2022

Cited by 3 | Viewed by 1472

Abstract

Background: Chronic or low-grade inflammation is a process where various immune cells are recruited from the periphery into adipose tissue. This event gives rise to localised inflammation, in addition to having a close interaction with cardiometabolic pathologies where the mediation of orphan receptors is observed. The aim of this study was to analyse the participation of the orphan receptors GPR21, GPR39, GPR82 and GPR6 in a chronic inflammatory process in 3T3-L1 cells. The 3T3-L1 cells were stimulated with TNF-α (5 ng/mL) for 60 min as an inflammatory model. Gene expression was measured by RT-qPCR. Results: We showed that the inflammatory stimulus of TNF-α in adipocytes decreased the expression of the orphan receptors GPR21, GPR26, GPR39, GPR82 and GPR6, which are related to low-grade inflammation. Conclusions: Our results suggest that GPR21 and GPR82 are modulated by glycine, it shows a possible protective role in the presence of an inflammatory environment in adipocytes, and they could be a therapeutic target to decrease the inflammation in some diseases related to low-grade inflammation such as diabetes, obesity and metabolic syndrome. Full article

(This article belongs to the Special Issue New Updates in Adipocytes and Adipose Tissue)

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16 pages, 2417 KiB

Open AccessArticle

Mulberry (Morus alba L.) Leaf Extract and 1-Deoxynojirimycin Improve Skeletal Muscle Insulin Resistance via the Activation of IRS-1/PI3K/Akt Pathway in db/db Mice

by Chae-Won Kang, Miey Park and Hae-Jeung Lee

Life 2022, 12(10), 1630; https://doi.org/10.3390/life12101630 - 18 Oct 2022

Cited by 10 | Viewed by 2541

Abstract

Mulberry (Morus alba L.) leaves have been used to lower blood glucose in patients with diabetes. We evaluated the effects of mulberry leaves extract (MLE) and 1-deoxynojirimycin (1-DNJ) in improving insulin resistance through the activation of the IRS-1/PI3K/Akt pathway in the skeletal muscle of db/db mice. Histological analysis revealed an amelioration of muscle deformation and increased muscle fiber size. MLE and 1-DNJ positively raised the protein expression of related glucose uptake and increased the translocation of glucose transporter type 4 (GLUT4) to the membrane. Furthermore, MLE and 1-DNJ activated the IRS-1/PI3K/Akt pathway in the skeletal muscle and, subsequently, modulated the protein levels of glycogen synthase kinase-3beta (GSK-3β) and glycogen synthase (GS), leading to elevated muscle glycogen content. These findings suggest that MLE and 1-DNJ supplementation improves insulin resistance by modulating the insulin signaling pathway in the skeletal muscle of db/db mice. Full article

(This article belongs to the Special Issue New Updates in Adipocytes and Adipose Tissue)

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16 pages, 1101 KiB

Open AccessReview

Obesity and Wound Healing: Focus on Mesenchymal Stem Cells

by Antonio Alma, Guya Diletta Marconi, Elena Rossi, Cristina Magnoni and Alessia Paganelli

Life 2023, 13(3), 717; https://doi.org/10.3390/life13030717 - 06 Mar 2023

Cited by 6 | Viewed by 4244

Abstract

Chronic wounds represent nowadays a major challenge for both clinicians and researchers in the regenerative setting. Obesity represents one of the major comorbidities in patients affected by chronic ulcers and therefore diverse studies aimed at assessing possible links between these two morbid conditions are currently ongoing. In particular, adipose tissue has recently been described as having metabolic and endocrine functions rather than serving as a mere fat storage deposit. In this setting, adipose-derived stem cells, a peculiar subset of mesenchymal stromal/stem cells (MSCs) located in adipose tissue, have been demonstrated to possess regenerative and immunological functions with a key role in regulating both adipocyte function and skin regeneration. The aim of the present review is to give an overview of the most recent findings on wound healing, with a special focus on adipose tissue biology and obesity. Full article

(This article belongs to the Special Issue New Updates in Adipocytes and Adipose Tissue)

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25 pages, 5175 KiB

Open AccessReview

Alternative Methods as Tools for Obesity Research: In Vitro and In Silico Approaches

by Juliana Helena Pamplona, Bernardo Zoehler, Patrícia Shigunov, María Julia Barisón, Vanessa Rossini Severo, Natalie Mayara Erich, Annanda Lyra Ribeiro, Cintia Delai da Silva Horinouchi, Andréia Akemi Suzukawa, Anny Waloski Robert, Ana Paula Ressetti Abud and Alessandra Melo de Aguiar

Life 2023, 13(1), 108; https://doi.org/10.3390/life13010108 - 30 Dec 2022

Cited by 1 | Viewed by 2603

Abstract

The study of adipogenesis is essential for understanding and treating obesity, a multifactorial problem related to body fat accumulation that leads to several life-threatening diseases, becoming one of the most critical public health problems worldwide. In this review, we propose to provide the highlights of the adipogenesis study based on in vitro differentiation of human mesenchymal stem cells (hMSCs). We list in silico methods, such as molecular docking for identification of molecular targets, and in vitro approaches, from 2D, more straightforward and applied for screening large libraries of substances, to more representative physiological models, such as 3D and bioprinting models. We also describe the development of physiological models based on microfluidic systems applied to investigate adipogenesis in vitro. We intend to identify the main alternative models for adipogenesis evaluation, contributing to the direction of preclinical research in obesity. Future directions indicate the association of in silico and in vitro techniques to bring a clear picture of alternative methods based on adipogenesis as a tool for obesity research. Full article

(This article belongs to the Special Issue New Updates in Adipocytes and Adipose Tissue)

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