Recent Advances in Adipokines—2nd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 31 August 2024 | Viewed by 6892

Special Issue Editor

Special Issue Information

Dear Colleagues,

This Special Issue, “Recent Advances on Adipokines—Second Edition”, will cover a selection of original research articles and review articles related to adipokines.

Soluble proteins produced from adipose tissue are referred to as adipokines irrespective of their cellular source. White fat tissue is organized into different depots in the body. Subcutaneous and visceral adipose tissues are the best studied compartments. Adipose tissues are also localized around organs such as the heart and kidneys. Brown adipose tissue differs greatly from white fat and has its own set of secreted hormones, the so-called “brown adipokines”.

To date, more than 500 adipokines have been described, and most of them are associated with overweight/obesity. Whilst levels of various adipokines are increased in serum of the obese, others decline. Associations between adipokines and cardiovascular diseases, insulin resistance, different types of cancers, and many more diseases have been identified. Further research has focused on the role of these proteins in immune responses, in autoimmune diseases and as antimicrobial peptides. Adipokines in serum, plasma, saliva or urine may emerge as diagnostic and/or prognostic biomarkers for various diseases.

Adipokine receptors are mostly not well characterized. Cell type and tissue expression, regulation using different metabolites and signalling pathways have to be studied in more detail. Adipokine receptor agonists/antagonists may finally become new therapeutic targets.

Prof. Dr. Christa Buechler
Guest Editor

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Keywords

  • adiponectin
  • receptor
  • agonist
  • biomarker
  • inflammation
  • cancer

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Published Papers (8 papers)

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Research

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15 pages, 1680 KiB  
Article
Diagnostic and Prognostic Value of Serum Leptin in Critically Ill Patients with Acute versus Acute-on-Chronic Liver Failure
by Philipp Hohlstein, Can Salvarcioglu, Maike R. Pollmanns, Jule K. Adams, Samira Abu Jhaisha, Elena Kabak, Albrecht Eisert, Karim Hamesch, Ralf Weiskirchen, Alexander Koch and Theresa H. Wirtz
Biomedicines 2024, 12(6), 1170; https://doi.org/10.3390/biomedicines12061170 - 24 May 2024
Viewed by 460
Abstract
Differentiation between acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) can be challenging in patients with de novo liver disease but is important to indicate the referral to a transplant center and urgency of organ allocation. Leptin, an adipocyte-derived cytokine that regulates [...] Read more.
Differentiation between acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) can be challenging in patients with de novo liver disease but is important to indicate the referral to a transplant center and urgency of organ allocation. Leptin, an adipocyte-derived cytokine that regulates energy storage and satiety, has multiple regulatory functions in the liver. We enrolled 160 critically ill patients with liver disease and 20 healthy individuals to measure serum leptin concentrations as a potential biomarker for diagnostic and prognostic purposes. Notably, patients with ALF had higher concentrations of serum leptin compared to patients with decompensated advanced chronic liver disease (dACLD) or ACLF (110 vs. 50 vs. 29 pg/mL, p < 0.001). Levels of serum leptin below 56 pg/mL excluded ALF in patients with acute hepatic disease, with a negative predictive value (NPV) of 98.8% in our cohort. Lastly, serum leptin did not show any dynamic changes within the first 48 h of ICU treatment, especially not in comparison with patients with ALF vs. ACLF or survivors vs. non-survivors. In conclusion, serum leptin may represent a helpful biomarker to exclude ALF in critically ill patients who present with acute liver dysfunction. Full article
(This article belongs to the Special Issue Recent Advances in Adipokines—2nd Edition)
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15 pages, 1718 KiB  
Article
Serum Adiponectin Predicts COVID-19 Severity
by Vlad Pavel, Ulrich Räth, Stephan Schmid, Sabrina Krautbauer, Dennis Keller, Pablo Amend, Martina Müller, Patricia Mester and Christa Buechler
Biomedicines 2024, 12(5), 1043; https://doi.org/10.3390/biomedicines12051043 - 9 May 2024
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Abstract
Adiponectin is primarily known for its protective role in metabolic diseases, and it also possesses immunoregulatory properties. Elevated levels of adiponectin have been observed in various inflammatory diseases. However, studies investigating adiponectin levels in the serum of COVID-19 patients have yielded conflicting results. [...] Read more.
Adiponectin is primarily known for its protective role in metabolic diseases, and it also possesses immunoregulatory properties. Elevated levels of adiponectin have been observed in various inflammatory diseases. However, studies investigating adiponectin levels in the serum of COVID-19 patients have yielded conflicting results. This study aimed to assess serum adiponectin levels in 26 healthy controls, as well as in 64 patients with moderate and 60 patients with severe COVID-19, to determine a potential association between serum adiponectin and the severity of COVID-19. Serum adiponectin levels in severe COVID-19 patients were significantly lower than in those with moderate disease and healthy controls, who exhibited similar serum adiponectin levels. Among patients with moderate disease, positive correlations were observed between serum adiponectin and C-reactive protein levels. Of note, serum adiponectin levels of severe COVID-19 cases were comparable between patients with and without dialysis or vasopressor therapy. Superinfection with bacteria did not exert a notable influence on serum adiponectin levels in patients with severe disease. Patients who were diagnosed with severe COVID-19 and vancomycin-resistant enterococci bacteremia showed a significant reduction in their serum adiponectin levels. An analysis conducted on the entire cohort, including both moderate and severe COVID-19 patients, showed that individuals who did not survive had lower serum adiponectin levels when compared to those who survived. In summary, this study highlights a decrease in serum adiponectin levels in severe COVID-19 cases, indicating the potential utility of adiponectin as an additional biomarker for monitoring disease severity in COVID-19 or critical illnesses in general. Full article
(This article belongs to the Special Issue Recent Advances in Adipokines—2nd Edition)
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11 pages, 1186 KiB  
Communication
Chemerin Levels in Individuals with Type 2 Diabetes and a Normal Weight versus Individuals with Type 2 Diabetes and Obesity: An Observational, Cross-Sectional Study
by Aishee B. Mukherji, Victoria Idowu, Lei Zhao, Lawrence L. K. Leung, Sa Shen, Latha Palaniappan and John Morser
Biomedicines 2024, 12(5), 983; https://doi.org/10.3390/biomedicines12050983 - 30 Apr 2024
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Abstract
Chemerin acts as both a chemotactic agent and an adipokine that undergoes proteolytic cleavage, converting inactive precursors into their active forms before being subsequently inactivated. Elevated chemerin levels are linked to obesity and type 2 diabetes mellitus (T2D). This study aimed to elucidate [...] Read more.
Chemerin acts as both a chemotactic agent and an adipokine that undergoes proteolytic cleavage, converting inactive precursors into their active forms before being subsequently inactivated. Elevated chemerin levels are linked to obesity and type 2 diabetes mellitus (T2D). This study aimed to elucidate the effects of T2D and obesity on chemerin levels by comparing plasma samples from individuals with a normal weight and T2D (BMI < 25; NWD group n = 22) with those from individuals who are overweight or obese and have T2D (BMI ≥ 25; OWD group n = 39). The total chemerin levels were similar in the NWD and OWD groups, suggesting that T2D may equalize the chemerin levels irrespective of obesity status. The cleavage of chemerin has been previously linked to myocardial infarction and stroke in NWD, with potential implications for inflammation and mortality. OWD plasma exhibited lower levels of cleaved chemerin than the NWD group, suggesting less inflammation in the OWD group. Here, we showed that the interaction between obesity and T2D leads to an equalization in the total chemerin levels. The cleaved chemerin levels and the associated inflammatory state, however, differ significantly, underscoring the complex relationship between chemerin, T2D, and obesity. Full article
(This article belongs to the Special Issue Recent Advances in Adipokines—2nd Edition)
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19 pages, 10417 KiB  
Article
Chemerin in Participants with or without Insulin Resistance and Diabetes
by Lei Zhao, Jonathan Zhou, Fahim Abbasi, Mohsen Fathzadeh, Joshua W. Knowles, Lawrence L. K. Leung and John Morser
Biomedicines 2024, 12(4), 924; https://doi.org/10.3390/biomedicines12040924 - 22 Apr 2024
Cited by 1 | Viewed by 857
Abstract
Chemerin is a chemokine/adipokine, regulating inflammation, adipogenesis and energy metabolism whose activity depends on successive proteolytic cleavages at its C-terminus. Chemerin levels and processing are correlated with insulin resistance. We hypothesized that chemerin processing would be higher in individuals with type 2 diabetes [...] Read more.
Chemerin is a chemokine/adipokine, regulating inflammation, adipogenesis and energy metabolism whose activity depends on successive proteolytic cleavages at its C-terminus. Chemerin levels and processing are correlated with insulin resistance. We hypothesized that chemerin processing would be higher in individuals with type 2 diabetes (T2D) and in those who are insulin resistant (IR). This hypothesis was tested by characterizing different chemerin forms by specific ELISA in the plasma of 18 participants with T2D and 116 without T2D who also had their insulin resistance measured by steady-state plasma glucose (SSPG) concentration during an insulin suppression test. This approach enabled us to analyze the association of chemerin levels with a direct measure of insulin resistance (SSPG concentration). Participants were divided into groups based on their degree of insulin resistance using SSPG concentration tertiles: insulin sensitive (IS, SSPG ≤ 91 mg/dL), intermediate IR (IM, SSPG 92–199 mg/dL), and IR (SSPG ≥ 200 mg/dL). Levels of different chemerin forms were highest in patients with T2D, second highest in individuals without T2D who were IR, and lowest in persons without T2D who were IM or IS. In the whole group, chemerin levels positively correlated with both degree of insulin resistance (SSPG concentration) and adiposity (BMI). Participants with T2D and those without T2D who were IR had the most proteolytic processing of chemerin, resulting in higher levels of both cleaved and degraded chemerin. This suggests that increased inflammation in individuals who have T2D or are IR causes more chemerin processing. Full article
(This article belongs to the Special Issue Recent Advances in Adipokines—2nd Edition)
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13 pages, 757 KiB  
Article
Altered Red Blood Cell Fatty Acid and Serum Adipokine Profiles in Subjects with Obesity
by Asier Léniz, Alfredo Fernández-Quintela, Sara Arranz, Kevin Portune, Itziar Tueros, Eunate Arana, Luis Castaño, Olaia Velasco and María P. Portillo
Biomedicines 2023, 11(12), 3320; https://doi.org/10.3390/biomedicines11123320 - 15 Dec 2023
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Abstract
Background: Adipokines, as well as the fatty acid profile of red blood cell (RBC) membranes, are known to play important roles in the development and progression of metabolic complications induced by obesity. Thus, the objective of this study is to compare the serum [...] Read more.
Background: Adipokines, as well as the fatty acid profile of red blood cell (RBC) membranes, are known to play important roles in the development and progression of metabolic complications induced by obesity. Thus, the objective of this study is to compare the serum adipokine profile and the RBC membrane fatty acid profile of normal-weight and obese adults, and to analyze their relationship with serum biochemical parameters. Methods: An observational case–control study was performed in 75 normal-weight and obese adult subjects. Biochemical serum parameters, eight serum adipokines and the RBC membrane fatty acid profiles were measured. Associations between parameters were established using regression analysis. Results: Subjects with obesity showed increased levels of leptin, fibroblast growth factor 21 (FGF21) and overexpressed nephroblastoma (NOV/CCN3), decreased adiponectin, and similar levels of vaspin and chemerin compared to normal-weight subjects. Significant positive and negative correlations were found with triglycerides and high-density lipoprotein-cholesterol (HDL-c), respectively. An increase in the total ω-6 fatty acids in the RBC membrane fatty acid profiles in subjects with obesity was observed, because of higher levels of both dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA), and decreased total ω-3 fatty acids, mainly due to lower levels of docosahexaenoic acid (DHA). The ω-6/ω-3 ratio in the RBCs was significantly higher, suggesting an inflammatory status, as was also suggested by a reduced adiponectin level. A negative association between DGLA and adiponectin, and a positive association between DHA and serum triglycerides, was observed. Conclusions: Important alterations in serum adipokine and RBC fatty acid profiles are found in subjects with obesity. Full article
(This article belongs to the Special Issue Recent Advances in Adipokines—2nd Edition)
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14 pages, 1612 KiB  
Article
Exploring the Relationship between Plasma Adiponectin, Gender, and Underlying Diseases in Severe Illness
by Patricia Mester, Ulrich Räth, Stephan Schmid, Martina Müller, Christa Buechler and Vlad Pavel
Biomedicines 2023, 11(12), 3287; https://doi.org/10.3390/biomedicines11123287 - 12 Dec 2023
Cited by 1 | Viewed by 916
Abstract
Adiponectin is low in obesity, plays a crucial role in metabolic health, and, moreover, possesses immunoregulatory properties. However, studies examining its levels in patients with systemic inflammatory response syndrome (SIRS) or sepsis have yielded conflicting results. While females typically have higher systemic adiponectin [...] Read more.
Adiponectin is low in obesity, plays a crucial role in metabolic health, and, moreover, possesses immunoregulatory properties. However, studies examining its levels in patients with systemic inflammatory response syndrome (SIRS) or sepsis have yielded conflicting results. While females typically have higher systemic adiponectin levels than males, research on sex-specific associations in this context is limited. In this study of 156 SIRS/sepsis patients, including those with liver cirrhosis, we aimed to explore the relationship between plasma adiponectin, body mass index (BMI), gender, disease severity, and underlying etiological conditions. Our findings revealed that patients with liver cirrhosis, who are susceptible to infections, exhibited elevated circulating adiponectin levels, irrespective of sex. When excluding cirrhosis patients, plasma adiponectin levels were similar between male SIRS/sepsis patients and controls but lower in female patients compared to female controls. Plasma adiponectin was inversely related to BMI in female but not male patients. Further analysis within the non-cirrhosis subgroup demonstrated no significant differences in adiponectin levels between sexes among SIRS, sepsis, and septic shock patients. Ventilation, dialysis, and vasopressor therapy had no discernible impact on adiponectin levels in either sex. A negative correlation between adiponectin and C-reactive protein (CRP) existed in males only. Notably, patients with pancreatitis showed the lowest plasma adiponectin concentrations, although sex-specific differences were not significant. Infection with Gram-negative or Gram-positive bacteria had minimal effects on plasma adiponectin levels in both sexes. However, infection with the severe acute respiratory syndrome coronavirus type 2 led to decreased adiponectin levels in females exclusively. Multivariate analysis considering all factors affecting plasma adiponectin levels in males or females identified BMI in females and CRP levels in males to predict plasma adiponectin levels in SIRS/sepsis patients. Additionally, our study observed a trend where the 25 patients who did not survive had higher plasma adiponectin levels, particularly among males. In summary, our investigation highlights the influence of underlying diseases and sex on plasma adiponectin levels in SIRS/sepsis patients, shedding light on potential implications for disease management and prognosis. Full article
(This article belongs to the Special Issue Recent Advances in Adipokines—2nd Edition)
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22 pages, 728 KiB  
Review
Obesity, Metabolic Syndrome, and Osteoarthritis Require Integrative Understanding and Management
by Veronica Mocanu, Daniel Vasile Timofte, Camelia-Mihaela Zară-Dănceanu and Luminita Labusca
Biomedicines 2024, 12(6), 1262; https://doi.org/10.3390/biomedicines12061262 - 6 Jun 2024
Viewed by 424
Abstract
Osteoarthritis (OA) is a progressive chronic disease affecting the articular joints, leading to pain and disability. Unlike traditional views that primarily link OA to aging, recent understanding portrays it as a multifactorial degenerative disease of the entire joint. Emerging research highlights metabolic and [...] Read more.
Osteoarthritis (OA) is a progressive chronic disease affecting the articular joints, leading to pain and disability. Unlike traditional views that primarily link OA to aging, recent understanding portrays it as a multifactorial degenerative disease of the entire joint. Emerging research highlights metabolic and immune dysregulation in OA pathogenesis, emphasizing the roles of obesity, dyslipidemia, and insulin resistance in altering joint homeostasis. Recent studies have increasingly focused on the complex role of white adipose tissue (WAT) in OA. WAT not only serves metabolic functions but also plays a critical role in systemic inflammation through the release of various adipokines. These adipokines, including leptin and adiponectin, have been implicated in exacerbating cartilage erosion and promoting inflammatory pathways within joint tissues. The overlapping global crises of obesity and metabolic syndrome have significantly impacted joint health. Obesity, now understood to contribute to mechanical joint overload and metabolic dysregulation, heightens the risk of developing OA, particularly in the knee. Metabolic syndrome compounds these risks by inducing chronic inflammation and altering macrophage activity within the joints. The multifaceted effects of obesity and metabolic syndrome extend beyond simple joint loading. These conditions disrupt normal joint function by modifying tissue composition, promoting inflammatory macrophage polarization, and impairing chondrocyte metabolism. These changes contribute to OA progression, highlighting the need for targeted therapeutic strategies that address both the mechanical and biochemical aspects of the disease. Recent advances in understanding the molecular pathways involved in OA suggest potential therapeutic targets. Interventions that modulate macrophage polarization, improve chondrocyte function, or normalize adipokine levels could serve as preventative or disease-modifying therapies. Exploring the role of diet, exercise, and pharmacological interventions in modulating these pathways offers promising avenues for reducing the burden of OA. Furthermore, such methods could prove cost-effective, avoiding the increase in access to healthcare. Full article
(This article belongs to the Special Issue Recent Advances in Adipokines—2nd Edition)
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17 pages, 1123 KiB  
Review
Influence of Adipokines on Metabolic Dysfunction and Aging
by Seongjoon Park and Isao Shimokawa
Biomedicines 2024, 12(4), 873; https://doi.org/10.3390/biomedicines12040873 - 15 Apr 2024
Viewed by 1034
Abstract
Currently, 30% of the global population is overweight or obese, with projections from the World Obesity Federation suggesting that this figure will surpass 50% by 2035. Adipose tissue dysfunction, a primary characteristic of obesity, is closely associated with an increased risk of metabolic [...] Read more.
Currently, 30% of the global population is overweight or obese, with projections from the World Obesity Federation suggesting that this figure will surpass 50% by 2035. Adipose tissue dysfunction, a primary characteristic of obesity, is closely associated with an increased risk of metabolic abnormalities, such as hypertension, hyperglycemia, and dyslipidemia, collectively termed metabolic syndrome. In particular, visceral fat accretion is considered as a hallmark of aging and is strongly linked to higher mortality rates in humans. Adipokines, bioactive peptides secreted by adipose tissue, play crucial roles in regulating appetite, satiety, adiposity, and metabolic balance, thereby rendering them key players in alleviating metabolic diseases and potentially extending health span. In this review, we elucidated the role of adipokines in the development of obesity and related metabolic disorders while also exploring the potential of certain adipokines as candidates for longevity interventions. Full article
(This article belongs to the Special Issue Recent Advances in Adipokines—2nd Edition)
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