International Journal of Molecular Sciences

Editorial

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Open AccessEditorial

Obesity and Obesity-Related Disorders—Editorial

by Grażyna Nowicka

Int. J. Mol. Sci. 2024, 25(14), 7954; https://doi.org/10.3390/ijms25147954 - 21 Jul 2024

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Abstract

Obesity and obesity-related complications, including various metabolic diseases and cancers, are significant health problems in developed and developing countries [...] Full article

(This article belongs to the Special Issue Obesity and Obesity Related Disorders)

Research

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19 pages, 3162 KiB

Open AccessArticle

Sex-Specific Effects of Long-Term Antipsychotic Drug Treatment on Adipocyte Tissue and the Crosstalk to Liver and Brain in Rats

by Karin Fehsel and Marie-Luise Bouvier

Int. J. Mol. Sci. 2024, 25(4), 2188; https://doi.org/10.3390/ijms25042188 - 11 Feb 2024

Cited by 1 | Viewed by 1450

Abstract

Antipsychotic drug (APD) medication can lead to metabolic dysfunctions and weight gain, which together increase morbidity and mortality. Metabolically active visceral adipose tissue (VAT) in particular plays a crucial role in the etiopathology of these metabolic dysregulations. Here, we studied the effect of [...] Read more.

Antipsychotic drug (APD) medication can lead to metabolic dysfunctions and weight gain, which together increase morbidity and mortality. Metabolically active visceral adipose tissue (VAT) in particular plays a crucial role in the etiopathology of these metabolic dysregulations. Here, we studied the effect of 12 weeks of drug medication by daily oral feeding of clozapine and haloperidol on the perirenal fat tissue as part of VAT of male and female Sprague Dawley rats in the context of complex former investigations on brain, liver, and blood. Adipocyte area values were determined, as well as triglycerides, non-esterified fatty acids (NEFAs), glucose, glycogen, lactate, malondialdehyde equivalents, ferric iron and protein levels of Perilipin-A, hormone-sensitive-lipase (HSL), hepcidin, glucose transporter-4 (Glut-4) and insulin receptor-ß (IR-ß). We found increased adipocyte mass in males, with slightly higher adipocyte area values in both males and females under clozapine treatment. Triglycerides, NEFAs, glucose and oxidative stress in the medicated groups were unchanged or slightly decreased. In contrast to controls and haloperidol-medicated rats, perirenal adipocyte mass and serum leptin levels were not correlated under clozapine. Protein expressions of perilipin-A, Glut-4 and HSL were decreased under clozapine treatment. IR-ß expression changed sex-specifically in the clozapine-medicated groups associated with higher hepcidin levels in the perirenal adipose tissue of clozapine-treated females. Taken together, clozapine and haloperidol had a smaller effect than expected on perirenal adipose tissue. The perirenal adipose tissue shows only weak changes in lipid and glucose metabolism. The main changes can be seen in the proteins examined, and probably in their effect on liver metabolism. Full article

(This article belongs to the Special Issue Obesity and Obesity Related Disorders)

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16 pages, 5014 KiB

Open AccessArticle

The Impact of Obesity on Diabetes Onset and Neovascularization in Mouse Models of Metabolic Stress

by Sai Pranathi Meda Venkata, Hainan Li, Liping Xu and Jie-Mei Wang

Int. J. Mol. Sci. 2024, 25(2), 1214; https://doi.org/10.3390/ijms25021214 - 19 Jan 2024

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Abstract

Animal models of metabolic disorders are essential to studying pathogenic mechanisms and developing therapies for diabetes, but the induction protocols vary, and sexual dimorphism often exists. In a chronic diabetic model of diet-induced obesity (DIO) and low-dose streptozotocin (STZ)-induced hyperglycemia, blood glucose and [...] Read more.

Animal models of metabolic disorders are essential to studying pathogenic mechanisms and developing therapies for diabetes, but the induction protocols vary, and sexual dimorphism often exists. In a chronic diabetic model of diet-induced obesity (DIO) and low-dose streptozotocin (STZ)-induced hyperglycemia, blood glucose and lipid profiles were measured. The high-fat (HF) diet damaged insulin sensitivity and increased triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, and liver lipid deposition. STZ increased blood glucose and liver fibrosis with less effects on blood lipids or liver lipid deposition. The combination of DIO and STZ treatments led to significant liver lipid deposition and fibrosis. Female mice showed delayed body weight gain on HF diet and resisted STZ-induced hyperglycemia. However, once they developed DIO, which occurs around 26 weeks of HF diet, the female mice were prone to STZ-induced hyperglycemia. In hindlimb ischemia, male mice in the DIO-STZ group showed significantly worse neovascularization compared with DIO or STZ groups. The DIO-STZ females showed significantly worse recovery than the DIO-STZ males. Our observations suggest that DIO-STZ is a plausible model for studying metabolic and cardiovascular disorders in obesity and diabetes. Moreover, the findings in female animals stress the need to assess sexual dimorphism and investigate the underlying mechanisms that contribute to the worse vasculopathy manifestations in females in metabolic models. Full article

(This article belongs to the Special Issue Obesity and Obesity Related Disorders)

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13 pages, 1916 KiB

Open AccessArticle

Cinnamyl Alcohol Attenuates Adipogenesis in 3T3-L1 Cells by Arresting the Cell Cycle

by Yae Rim Choi, Young-Suk Kim and Min Jung Kim

Int. J. Mol. Sci. 2024, 25(2), 693; https://doi.org/10.3390/ijms25020693 - 5 Jan 2024

Cited by 3 | Viewed by 1779

Abstract

Cinnamyl alcohol (CA) is an aromatic compound found in several plant-based resources and has been shown to exert anti-inflammatory and anti-microbial activities. However, the anti-adipogenic mechanism of CA has not been sufficiently studied. The present study aimed to investigate the effect and mechanism [...] Read more.

Cinnamyl alcohol (CA) is an aromatic compound found in several plant-based resources and has been shown to exert anti-inflammatory and anti-microbial activities. However, the anti-adipogenic mechanism of CA has not been sufficiently studied. The present study aimed to investigate the effect and mechanism of CA on the regulation of adipogenesis. As evidenced by Oil Red O staining, Western blotting, and real-time PCR (RT-PCR) analyses, CA treatment (6.25–25 μM) for 8 d significantly inhibited lipid accumulation in a concentration-dependent manner and downregulated adipogenesis-related markers (peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), fatty acid binding protein 4 (FABP4), adiponectin, fatty acid synthase (FAS)) in 3-isobutyl-1-methylxanthine, dexamethasone, and insulin(MDI)-treated 3T3-L1 adipocytes. In particular, among the various differentiation stages, the early stage of adipogenesis was critical for the inhibitory effect of CA. Cell cycle analysis using flow cytometry and Western blotting showed that CA effectively inhibited MDI-induced initiation of mitotic clonal expansion (MCE) by arresting the cell cycle in the G₀/G₁ phase and downregulating the expression of C/EBPβ, C/EBPδ, and cell cycle markers (cyclin D1, cyclin-dependent kinase 6 (CDK6), cyclin E1, CDK2, and cyclin B1). Moreover, AMP-activated protein kinase α (AMPKα), acetyl-CoA carboxylase (ACC), and extracellular signal-regulated kinase 1/2 (ERK1/2), markers of upstream signaling pathways, were phosphorylated during MCE by CA. In conclusion, CA can act as an anti-adipogenic agent by inhibiting the AMPKα and ERK1/2 signaling pathways and the cell cycle and may also act as a potential therapeutic agent for obesity. Full article

(This article belongs to the Special Issue Obesity and Obesity Related Disorders)

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18 pages, 4232 KiB

Open AccessArticle

Rab18 Drift in Lipid Droplet and Endoplasmic Reticulum Interactions of Adipocytes under Obesogenic Conditions

by Jaime López-Alcalá, M. Carmen Soler-Vázquez, Carmen Tercero-Alcázar, Julia Sánchez-Ceinos, Rocío Guzmán-Ruiz, María M. Malagón and Ana Gordon

Int. J. Mol. Sci. 2023, 24(24), 17177; https://doi.org/10.3390/ijms242417177 - 6 Dec 2023

Cited by 1 | Viewed by 1562

Abstract

The adipose tissue stores excess energy in the form of neutral lipids within adipocyte lipid droplets (LDs). The correct function of LDs requires the interaction with other organelles, such as the endoplasmic reticulum (ER) as well as with LD coat-associated proteins, including Rab18, [...] Read more.

The adipose tissue stores excess energy in the form of neutral lipids within adipocyte lipid droplets (LDs). The correct function of LDs requires the interaction with other organelles, such as the endoplasmic reticulum (ER) as well as with LD coat-associated proteins, including Rab18, a mediator of intracellular lipid trafficking and ER–LD interaction. Although perturbations of the inter-organelle contact sites have been linked to several diseases, such as cancer, no information regarding ER–LD contact sites in dysfunctional adipocytes from the obese adipose tissue has been published to date. Herein, the ER–LD connection and Rab18 distribution at ER–LD contact sites are examined in adipocytes challenged with fibrosis and inflammatory conditions, which represent known hallmarks of the adipose tissue in obesity. Our results show that adipocytes differentiated in fibrotic conditions caused ER fragmentation, the expansion of ER–LD contact sites, and modified Rab18 dynamics. Likewise, adipocytes exposed to inflammatory conditions favored ER–LD contact, Rab18 accumulation in the ER, and Rab18 redistribution to large LDs. Finally, our studies in human adipocytes supported the suggestion that Rab18 transitions to the LD coat from the ER. Taken together, our results suggest that obesity-related pathogenic processes alter the maintenance of ER–LD interactions and interfere with Rab18 trafficking through these contact sites. Full article

(This article belongs to the Special Issue Obesity and Obesity Related Disorders)

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20 pages, 3814 KiB

Open AccessArticle

Dipeptidyl Peptidase 4 Stimulation Induces Adipogenesis-Related Gene Expression of Adipose Stromal Cells

by Hsiao-Chi Lai, Pei-Hsuan Chen, Chia-Hua Tang and Lee-Wei Chen

Int. J. Mol. Sci. 2023, 24(22), 16101; https://doi.org/10.3390/ijms242216101 - 8 Nov 2023

Cited by 3 | Viewed by 1621

Abstract

Adipogenesis has emerged as a new therapeutic target for regulating metabolism and achieving anti-inflammatory and anti-atherosclerotic effects via the release of adiponectin. However, at present, the effects and mechanism of action of dipeptidyl peptidase 4 (DPP4) stimulation on adiponectin production and adipogenesis have [...] Read more.

Adipogenesis has emerged as a new therapeutic target for regulating metabolism and achieving anti-inflammatory and anti-atherosclerotic effects via the release of adiponectin. However, at present, the effects and mechanism of action of dipeptidyl peptidase 4 (DPP4) stimulation on adiponectin production and adipogenesis have not been clarified. Here, we investigated the effects of DPP4 stimulation with monocyte chemoattractant protein-1 (MCP-1) on platelet-derived growth factor receptor alpha (PDGFRα) expression in adipose tissue and blood adiponectin levels. Stromal vascular fractions (SVFs) purified from human subcutaneous adipose tissue and inguinal adipose tissue of obese and diabetic (Lepr^db/db) mice were treated with 50 ng of MCP-1 and plasma from control (Lepr^+/+) mice supplemented with 10 ng or 50 ng of MCP-1. Treatment of SVFs from human subcutaneous adipose tissues with 50 ng of MCP-1 significantly increased AdipoQ, DPP4, peroxisome proliferator-activated receptor gamma (PPARγ), fatty-acid-binding protein (FABP4), and SERBF1 mRNA expression. MCP-1-supplemented plasma increased adiponectin, CCAAT-Enhancer-binding protein alpha (C/EBPα), DPP4, IL-33, and PDGFRα mRNA expression and adiponectin and DPP4 protein expression, while decreasing the expression of IL-10 mRNA in SVFs compared with the levels in the plasma treatment group. MCP-1-supplemented plasma was shown to increase PPARγ, PPARγ2, adiponectin, DPP4, and FABP4 and decrease IL-10 mRNA expression in PDGFRα cells from adipose tissue. Meanwhile, MCP-1-supplemented plasma increased MCP-1, PDGFRα, TNFα, adiponectin, and IL-1β and decreased IL-10 and FOXP3 mRNA expression in DPP4 cells. Moreover, the injection of MCP-1-supplemented plasma into adipose tissue increased the proportion of DPP4⁺ cells among PDGFRα⁺ cells from adipose tissue and plasma adiponectin levels of Lepr^db/db mice compared with the levels in the plasma injection group. Our results demonstrate that DPP4⁺ cells are important adipose progenitor cells. Stimulation of DPP4 with MCP-1 increases adipogenesis-related gene expression and the population of DPP4⁺ cells among PDGFRα⁺ cells in SVFs and blood adiponectin levels. DPP4 stimulation could be a novel therapy to increase local adipogenesis and systemic adiponectin levels. Full article

(This article belongs to the Special Issue Obesity and Obesity Related Disorders)

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17 pages, 3953 KiB

Open AccessArticle

Exposure to Chlorpyrifos Alters Proliferation, Differentiation and Fatty Acid Uptake in 3T3-L1 Cells

by Magdalena Czajka, Krzysztof Sawicki, Magdalena Matysiak-Kucharek, Marcin Kruszewski, Jacek Kurzepa, Paulina Wojtyła-Buciora and Lucyna Kapka-Skrzypczak

Int. J. Mol. Sci. 2023, 24(22), 16038; https://doi.org/10.3390/ijms242216038 - 7 Nov 2023

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Abstract

Organophosphorus pesticides (OPs) are important factors in the etiology of many diseases, including obesity and type 2 diabetes mellitus. The aim of this study was to investigate the effect of a representative of OPs, chlorpyrifos (CPF), on viability, proliferation, differentiation, and fatty acid [...] Read more.

Organophosphorus pesticides (OPs) are important factors in the etiology of many diseases, including obesity and type 2 diabetes mellitus. The aim of this study was to investigate the effect of a representative of OPs, chlorpyrifos (CPF), on viability, proliferation, differentiation, and fatty acid uptake in 3T3-L1 cells. The effect of CPF exposure on preadipocyte proliferation was examined by the MTT, NR, and BrdU assays. The impact of CPF exposure on the differentiation of preadipocytes into mature adipocytes was evaluated by Oil Red O staining and RT-qPCR. The effect of CPF on free fatty acid uptake in adipocytes was assessed with the fluorescent dye BODIPY. Our experiments demonstrated that exposure to CPF decreased the viability of 3T3-L1 cells; however, it was increased when the cells were exposed to low concentrations of the pesticide. Exposure to CPF inhibited the proliferation and differentiation of 3T3-L1 preadipocytes. CPF exposure resulted in decreased lipid accumulation, accompanied by down-regulation of the two key transcription factors in adipogenesis: C/EBPα and PPARγ. Exposure to CPF increased basal free fatty acid uptake in fully differentiated adipocytes but decreased this uptake when CPF was added during the differentiation process. Increased free fatty acid accumulation in fully differentiated adipocytes may suggest that CPF leads to adipocyte hypertrophy, one of the mechanisms leading to obesity, particularly in adults. It can therefore be concluded that CPF may disturb the activity of preadipocytes and adipocytes, although the role of this pesticide in the development of obesity requires further research. Full article

(This article belongs to the Special Issue Obesity and Obesity Related Disorders)

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16 pages, 3094 KiB

Open AccessArticle

Four-and-a-Half LIM-Domain Protein 2 (FHL2) Induces Neuropeptide Y (NPY) in Macrophages in Visceral Adipose Tissue and Promotes Diet-Induced Obesity

by Judith Sommer, Hanna Ehnis, Tatjana Seitz, Julia Schneider, Andreas B. Wild, Sandra Moceri, Christa Buechler, Aline Bozec, Georg F. Weber, Susanne Merkel, Ruth Beckervordersandforth, Alexander Steinkasserer, Roland Schüle, Jonel Trebicka, Arndt Hartmann, Anja Bosserhoff, Stephan von Hörsten, Peter Dietrich and Claus Hellerbrand

Int. J. Mol. Sci. 2023, 24(19), 14943; https://doi.org/10.3390/ijms241914943 - 6 Oct 2023

Cited by 1 | Viewed by 1761

Abstract

Obesity is characterized by the expansion of the adipose tissue, usually accompanied by inflammation, with a prominent role of macrophages infiltrating the visceral adipose tissue (VAT). This chronic inflammation is a major driver of obesity-associated comorbidities. Four-and-a-half LIM-domain protein 2 (FHL2) is a [...] Read more.

Obesity is characterized by the expansion of the adipose tissue, usually accompanied by inflammation, with a prominent role of macrophages infiltrating the visceral adipose tissue (VAT). This chronic inflammation is a major driver of obesity-associated comorbidities. Four-and-a-half LIM-domain protein 2 (FHL2) is a multifunctional adaptor protein that is involved in the regulation of various biological functions and the maintenance of the homeostasis of different tissues. In this study, we aimed to gain new insights into the expression and functional role of FHL2 in VAT in diet-induced obesity. We found enhanced FHL2 expression in the VAT of mice with Western-type diet (WTD)-induced obesity and obese humans and identified macrophages as the cellular source of enhanced FHL2 expression in VAT. In mice with FHL2 deficiency (FHL2^KO), WTD feeding resulted in reduced body weight gain paralleled by enhanced energy expenditure and uncoupling protein 1 (UCP1) expression, indicative of activated thermogenesis. In human VAT, FHL2 was inversely correlated with UCP1 expression. Furthermore, macrophage infiltration and the expression of the chemokine MCP-1, a known promotor of macrophage accumulation, was significantly reduced in WTD-fed FHL2^KO mice compared with wild-type (wt) littermates. While FHL2 depletion did not affect the differentiation or lipid metabolism of adipocytes in vitro, FHL2 depletion in macrophages resulted in reduced expressions of MCP-1 and the neuropeptide Y (NPY). Furthermore, WTD-fed FHL2^KO mice showed reduced NPY expression in VAT compared with wt littermates, and NPY expression was enhanced in VAT resident macrophages of obese individuals. Stimulation with recombinant NPY induced not only UCP1 expression and lipid accumulation but also MCP-1 expression in adipocytes. Collectively, these findings indicate that FHL2 is a positive regulator of NPY and MCP-1 expression in macrophages and herewith closely linked to the mechanism of obesity-associated lipid accumulation and inflammation in VAT. Thus, FHL2 appears as a potential novel target to interfere with the macrophage–adipocyte crosstalk in VAT for treating obesity and related metabolic disorders. Full article

(This article belongs to the Special Issue Obesity and Obesity Related Disorders)

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17 pages, 2269 KiB

Open AccessArticle

Refining Evaluation of Bone Mass and Adipose Distribution in Dunnigan Syndrome

by Mariana Lima Mascarenhas Moreira, Iana Mizumukai de Araújo, Sandra Yasuyo Fukada, Lucas Gabriel R. Venturini, Natalia Rossin Guidorizzi, Carlos Ernesto Garrido, Clifford J. Rosen and Francisco José Albuquerque de Paula

Int. J. Mol. Sci. 2023, 24(17), 13118; https://doi.org/10.3390/ijms241713118 - 23 Aug 2023

Cited by 1 | Viewed by 1593

Abstract

Familial partial lipodystrophies (FPLD) are rare diseases characterized by selective loss of subcutaneous adipose tissue at different sites. This cross-sectional observational study aimed to estimate adipose tissue in the bone marrow (BMAT), intra (IMCL) and extra-myocyte lipids (EMCL), and define the bone phenotype [...] Read more.

Familial partial lipodystrophies (FPLD) are rare diseases characterized by selective loss of subcutaneous adipose tissue at different sites. This cross-sectional observational study aimed to estimate adipose tissue in the bone marrow (BMAT), intra (IMCL) and extra-myocyte lipids (EMCL), and define the bone phenotype in the context of FPLD2/Dunnigan syndrome (DS). The subjects comprised 23 controls (C) and 18 DS patients, matched by age, weight and height. Blood samples, dual-energy X-ray absorptiometry for bone mineral density (BMD) and trabecular bone score (TBS) and 1H-spectroscopy using magnetic resonance to estimate BMAT in the lumbar spine, IMCL, EMCL and osteoclastogenesis were assessed. The prevalence of diabetes mellitus was 78% in DS patients. Glucose, HbA1c, triglycerides, insulin and HOMA-IR levels were elevated in DS, whereas HDLc, 25(OH)D, PTH and osteocalcin levels were reduced. BMD was similar between groups at all sites, except 1/3 radius, which was lower in DS group. TBS was reduced in DS. DS presented increased osteoclastogenesis and elevated BMAT, with greater saturation levels and higher IMCL than the C group. HOMA-IR and EMCL were negatively associated with TBS; osteocalcin and EMCL were correlated negatively with BMD. This study contributes to refining the estimation of adipose tissue in DS by showing increased adiposity in the lumbar spine and muscle tissue. DXA detected lower TBS and BMD in the 1/3 radius, suggesting impairment in bone quality and that bone mass is mainly affected in the cortical bone. Full article

(This article belongs to the Special Issue Obesity and Obesity Related Disorders)

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12 pages, 815 KiB

Open AccessArticle

Irisin as a Novel Biomarker of Subclinical Atherosclerosis in Severe Obesity

by Júlia Carmona-Maurici, Araceli Rosa, Natalia Azcona-Granada, Elionora Peña, David Ricart-Jané, Anna Viñas, Maria Dolores López-Tejero, Joan Carles Domingo, Antonio Miñarro, Juan Antonio Baena-Fustegueras, Julia Peinado-Onsurbe and Eva Pardina

Int. J. Mol. Sci. 2023, 24(9), 8171; https://doi.org/10.3390/ijms24098171 - 3 May 2023

Cited by 2 | Viewed by 2332

Abstract

Severe obesity (SO) can accelerate atherosclerosis and the onset of acute cardiovascular events. The diagnosis of atherosclerosis in the context of a high body mass index (BMI) can be challenging, making the identification of biomarkers clinically relevant. We aimed to assess the usefulness [...] Read more.

Severe obesity (SO) can accelerate atherosclerosis and the onset of acute cardiovascular events. The diagnosis of atherosclerosis in the context of a high body mass index (BMI) can be challenging, making the identification of biomarkers clinically relevant. We aimed to assess the usefulness of irisin as a biomarker for subclinical atherosclerosis in participants with SO. This prospective observational study included 61 participants undergoing bariatric surgery for SO, defined as a BMI >40 kg/m² or >35 kg/m² with at least one comorbidity. Atherosclerotic plaques were detected by ultrasound. Plasma samples were obtained 1 month before and at 6 and 12 months after bariatric surgery to measure irisin by ELISA. Additionally, subcutaneous samples of adipose tissue were taken and genotyped to identify irisin polymorphism rs3480. Irisin levels were positively correlated with BMI (r = 0.23, p = 0.0064), negatively correlated with atheroma-related parameters (e.g., carotid intima-media thickness), and lower in subjects with atheroma (p < 0.0002). Irisin also showed good overall accuracy for discriminating plaque presence (AUC, 0.81; 95% CI, 0.6956–0.9156). However, the rs3480 polymorphism correlated with neither the irisin levels nor the presence of atheromas. Iirisin could identify subclinical atherosclerosis in SO and might facilitate clinical diagnosis. Full article

(This article belongs to the Special Issue Obesity and Obesity Related Disorders)

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13 pages, 2624 KiB

Open AccessArticle

The Effects of Neuropeptide B on Proliferation and Differentiation of Porcine White Preadipocytes into Mature Adipocytes

by Tatiana Wojciechowicz, Paweł A. Kolodziejski, Maria Billert, Mathias Z. Strowski, Krzysztof W. Nowak and Marek Skrzypski

Int. J. Mol. Sci. 2023, 24(7), 6096; https://doi.org/10.3390/ijms24076096 - 23 Mar 2023

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Abstract

Neuropeptide B (NPB) affects energy homeostasis and metabolism by binding and activating NPBWR1 and NPBWR2 in humans and pigs. Recently, we reported that NPB promotes the adipogenesis of rat white and brown preadipocytes as well as 3T3-L1 cells. In the present study, we [...] Read more.

Neuropeptide B (NPB) affects energy homeostasis and metabolism by binding and activating NPBWR1 and NPBWR2 in humans and pigs. Recently, we reported that NPB promotes the adipogenesis of rat white and brown preadipocytes as well as 3T3-L1 cells. In the present study, we evaluated the effects of NPB on the proliferation and differentiation of white porcine preadipocytes into mature adipocytes. We identified the presence of NPB, NPBWR1, and NPBWR2 on the mRNA and protein levels in porcine white preadipocytes. During the differentiation process, NPB increased the mRNA expression of PPARγ, C/EBPβ, C/EBPα, PPARγ, and C/EBPβ protein production in porcine preadipocytes. Furthermore, NPB stimulated lipid accumulation in porcine preadipocytes. Moreover, NPB promoted the phosphorylation of the p38 kinase in porcine preadipocytes, but failed to induce ERK1/2 phosphorylation. NPB failed to stimulate the expression of C/EBPβ in the presence of the p38 inhibitor. Taken together, we report that NPB promotes the differentiation of porcine preadipocytes via a p38-dependent mechanism. Full article

(This article belongs to the Special Issue Obesity and Obesity Related Disorders)

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14 pages, 1973 KiB

Open AccessArticle

Increased Number of Mucosal-Associated Invariant T Cells Is Associated with the Inhibition of Nonalcoholic Fatty Liver Disease in High Fat Diet–Fed Mice

by Haruka Kishi, Isao Usui, Teruo Jojima, Shiho Fujisaka, Sho Wakamatsu, Yuiko Mizunuma-Inoue, Takafumi Niitani, Shintaro Sakurai, Toshie Iijima, Takuya Tomaru, Kazuyuki Tobe and Yoshimasa Aso

Int. J. Mol. Sci. 2022, 23(23), 15309; https://doi.org/10.3390/ijms232315309 - 4 Dec 2022

Cited by 2 | Viewed by 1995

Abstract

Nonalcoholic fatty liver disease (NAFLD) is an emerging worldwide health concern. The disease may involve immune cells including T cells, but little is known about the role(s) of the innate-like T cells in the liver. Furthermore, the most abundant innate-like T cells in [...] Read more.

Nonalcoholic fatty liver disease (NAFLD) is an emerging worldwide health concern. The disease may involve immune cells including T cells, but little is known about the role(s) of the innate-like T cells in the liver. Furthermore, the most abundant innate-like T cells in the human liver are mucosal-associated invariant T (MAIT) cells, but the involvement of MAIT cells in NAFLD remains largely unexplored because of their paucity in mice. In this study, we used a novel mouse line, Vα19, in which the number of MAIT cells is equivalent to or greater than that in humans. Compared with the control mice, Vα19 mice fed a high-fat diet (HFD) exhibited a reduction in lipid accumulation, NAFLD activity score, and transcripts relevant to lipogenesis. In addition, serum triglyceride and non-esterified fatty acids were lower in Vα19 mice fed normal chow or HFD. In contrast, the Vα19 mice showed little or no change in glucose tolerance, insulin sensitivity, inflammation in adipose tissues, or intestinal permeability compared with the controls, irrespective of diet. These results suggest that the presence of MAIT cells is associated with reduced lipogenesis and lipid accumulation in the liver; however, further studies are needed to clarify the role of MAIT cells in hepatic lipid metabolism. Full article

(This article belongs to the Special Issue Obesity and Obesity Related Disorders)

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14 pages, 858 KiB

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Brown Adipose Tissue: A New Potential Target for Glucagon-like Peptide 1 Receptor Agonists in the Treatment of Obesity

by Tim Hropot, Rok Herman, Andrej Janez, Luka Lezaic and Mojca Jensterle

Int. J. Mol. Sci. 2023, 24(10), 8592; https://doi.org/10.3390/ijms24108592 - 11 May 2023

Cited by 10 | Viewed by 4240

Abstract

Adipose tissue can be divided into white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue, according to the differences in morphology. WAT acts as a buffer for increased energy intake and decreased energy expenditure during the development of obesity, resulting [...] Read more.

Adipose tissue can be divided into white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue, according to the differences in morphology. WAT acts as a buffer for increased energy intake and decreased energy expenditure during the development of obesity, resulting in visceral and ectopic WAT accumulation. These WAT depots are strongly associated with chronic systemic inflammation, insulin resistance, and cardiometabolic risk related to obesity. They represent a primary weight loss target in anti-obesity management. Second-generation anti-obesity medications glucagon-like peptide-1 receptor agonists (GLP-1RAs) cause weight loss and improve body composition by reducing visceral and ectopic fat depots of WAT, resulting in improved cardiometabolic health. Recently, the understanding of the physiological significance of BAT beyond its primary function in generating heat through non-shivering thermogenesis has been expanded. This has raised scientific and pharmaceutical interest in the manipulation of BAT to further enhance weight reduction and body weight maintenance. This narrative review focuses on the potential impact of GLP-1 receptor agonism on BAT, particularly in human clinical studies. It provides an overview of the role of BAT in weight management and highlights the need for further research to elucidate the mechanisms by which GLP-1RAs affect energy metabolism and weight loss. Despite encouraging preclinical data, limited clinical evidence supports the notion that GLP-1RAs contribute to BAT activation. Full article

(This article belongs to the Special Issue Obesity and Obesity Related Disorders)

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3 pages, 199 KiB

Open AccessComment

Comment on Lai et al. Dipeptidyl Peptidase 4 Stimulation Induces Adipogenesis-Related Gene Expression of Adipose Stromal Cells. Int. J. Mol. Sci. 2023, 24, 16101

by Oscar J. Cordero, Martin Kotrulev and Iria Gomez-Touriño

Int. J. Mol. Sci. 2024, 25(13), 7093; https://doi.org/10.3390/ijms25137093 - 28 Jun 2024

Cited by 1 | Viewed by 772

Abstract

Adiponectin is a circulating hormone secreted by adipose tissue that exerts, unlike other adipokines such as leptin, anti-inflammatory, anti-atherosclerotic and other protective effects on health. Adiponectin receptor agonists are being tested in clinical trials and are expected to show benefits in many diseases. [...] Read more.

Adiponectin is a circulating hormone secreted by adipose tissue that exerts, unlike other adipokines such as leptin, anti-inflammatory, anti-atherosclerotic and other protective effects on health. Adiponectin receptor agonists are being tested in clinical trials and are expected to show benefits in many diseases. In a recent article, LW Chen’s group used monocyte chemoattractant protein-1 (MCP-1/CCL2) to improve plasma levels of adiponectin, suggesting the involvement of dipeptidyl peptidase 4 (DPP4/CD26) in the mechanism. Here, we discuss the significance of the role of DPP4, favoring the increase in DPP4-positive interstitial progenitor cells, a finding that fits with the greater stemness and persistence of other DPP4/CD26-positive cells. Full article

(This article belongs to the Special Issue Obesity and Obesity Related Disorders)

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